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Lifestyle Intervention Strategies for Type 2 Diabetes
Management
A thesis submitted to the University of Adelaide
for the degree of Doctor of Philosophy
Thomas Philip Wycherley
Bachelor of Science (Physiology) [Honours]
Bachelor of Education (Secondary)
Bachelor of Applied Science (Human Movement)
University of Adelaide
Faculty of Health Sciences, School of Medical Sciences, Discipline of Physiology
AND
Commonwealth Scientific and Industrial Research Organisation
Food and Nutritional Sciences
December 2010
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TABLE OF CONTENTS
SUMMARY ...................................................................................................................... i
DECLARATION ............................................................................................................ iv
ACKNOWLEDGEMENTS ........................................................................................... vi
AUTHOR STATEMENTS........................................................................................... viii Publication 1: ............................................................................................................. viii
Publication 2: ............................................................................................................... xi Publication 3: ............................................................................................................. xiv
PUBLICATIONS ARISING FROM THESIS ........................................................... xvii
OTHER PUBLICATIONS ARISING DURING CANDIDATURE ......................... xviii CONFERENCE PRESENTATIONS DURING CANDIDATURE ............................ xix
International ............................................................................................................... xix
National ...................................................................................................................... xix
ABBREVIATIONS ...................................................................................................... xxi Chapter 1 & Chapter 5 ................................................................................................ xxi
Chapter 2 .................................................................................................................... xxi Chapter 3 ................................................................................................................... xxii
Chapter 4 ................................................................................................................... xxii
CHAPTER 1: ................................................................................................................... 1
RESEARCH BACKGROUND ...................................................................................... 1
1.1. Obesity Prevalence ..................................................................................... 1
1.2. Type 2 Diabetes Pathogenesis .................................................................... 3
1.2.1. Figure 1: ................................................................................................... 4
1.2.2. Figure 2: ................................................................................................... 6
1.3. Type 2 Diabetes Diagnosis ......................................................................... 6
1.4. Type 2 Diabetes Prevalence ........................................................................ 7
1.5. Type 2 Diabetes Consequences and Cost .................................................... 8
1.6. Interventional Strategies for Type 2 Diabetes ............................................. 9
1.7. Caloric Restriction for Weight Loss.......................................................... 11
1.8. Fat-Free Mass and Weight Loss ............................................................... 12
1.9. Current Nutrition Recommendations ........................................................ 13
1.10. High Protein, Low Fat Diets ..................................................................... 15
1.11. High Protein Diets and Health .................................................................. 17
1.11.1. Figure 3: ............................................................................................. 22
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1.11.2. Table 1: ............................................................................................... 26
1.11.3. Table 1: Continued .............................................................................. 27
1.12. Dietary Protein, Body Composition and Muscle Protein Synthesis ........... 28
1.13. Benefits of Physical Activity and Exercise ............................................... 29
1.14. Exercise Training during Weight Loss ...................................................... 30
1.15. Current Exercise Recommendations ......................................................... 31
1.16. Benefits of Resistance Exercise Training .................................................. 33
1.17. Resistance Exercise Training during Weight Loss .................................... 33
1.18. High Protein Hypocaloric Diets and Resistance Exercise Training in Combination ............................................................................................................ 36
1.18.1. Figure 4: ............................................................................................. 37
1.19. Timing of Ingestion of Protein Relative to Resistance Exercise on Muscle Protein Synthesis ..................................................................................................... 41
1.20. Timing of Ingestion of Protein Relative to Resistance Exercise on Muscle Accretion under Eucaloric Conditions ...................................................................... 43
1.21. Timing of Ingestion of Protein Relative to Resistance Exercise on Muscle Accretion under Hypocaloric Conditions ................................................................. 46
1.22. Barriers to Healthy Lifestyle Behaviours .................................................. 47
1.23. Barriers and Facilitators for Adherence to a Diet ...................................... 49
1.24. Barriers and Facilitators to an Exercise Program....................................... 50
1.25. Barriers and Facilitators to Continuing an Established Diet and Exercise Based Lifestyle Intervention Program ...................................................................... 51
1.26. Specific Aims of this Thesis ..................................................................... 52
CHAPTER 2: ................................................................................................................. 54
A HIGH PROTEIN DIET WITH RESISTANCE EXERCISE TRAINING IMPROVES WEIGHT LOSS AND BODY COMPOSITION IN OVERWEIGHT AND OBESE PATIENTS WITH TYPE 2 DIABETES ...................................................................... 54
2.1. Summary .................................................................................................. 55
2.2. Publication 1 ............................................................................................ 56
CHAPTER 3: ................................................................................................................. 64
TIMING OF PROTEIN INGESTION RELATIVE TO RESISTANCE EXERCISE TRAINING DOES NOT INFLUENCE BODY COMPOSITION, ENERGY EXPENDITURE, GLYCEMIC CONTROL OR CARDIOMETABOLIC RISK FACTORS IN A HYPOCALORIC, HIGH PROTEIN, LOW FAT DIET IN PATIENTS WITH TYPE 2 DIABETES ......................................................................................... 64
3.1. Summary .................................................................................................. 65
3.2. Publication 2 ............................................................................................ 66
CHAPTER 4: ................................................................................................................. 75
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SELF-REPORTED FACILITATORS OF AND IMPEDIMENTS TO MAINTENANCE OF HEALTHY LIFESTYLE BEHAVIOURS FOLLOWING A SUPERVISED RESEARCH-BASED LIFESTYLE INTERVENTION PROGRAM IN PATIENTS WITH TYPE 2 DIABETES ......................................................................................... 75
4.1. Summary .................................................................................................. 76
4.2. Publication 3 ............................................................................................ 78
4.2.1. ABSTRACT ........................................................................................... 79
4.2.2. INTRODUCTION: ................................................................................. 81
4.2.3. METHODS: ........................................................................................... 82
4.2.4. RESULTS and DISCUSSION: ............................................................... 84
4.2.4.1. Weight Loss ...................................................................................... 84
4.2.4.2. Reasons for participating in the RLP ................................................. 84
4.2.4.3. Ease of participation and reasons for persisting ................................. 85
4.2.4.4. Difficulty in maintaining the dietary plan and routine post-RLP ........ 86
4.2.4.5. Strategies used for continuation of the dietary plan post-RLP ............ 89
4.2.4.6. The importance of supervision and monitoring for dietary compliance during the RLP ................................................................................................. 89
4.2.4.7. Continuation of exercise participation post-RLP ............................... 90
4.2.4.8. Impediments to exercise participation post-RLP................................ 92
4.2.4.9. Research Limitation .......................................................................... 93
4.2.5. CONCLUSION ...................................................................................... 94
4.2.6. ACKNOWLEDGEMENTS: ................................................................... 95
4.2.7. AUTHOR CONTRIBUTIONS: .............................................................. 95
4.2.8. REFERENCES: ...................................................................................... 95
CHAPTER 5: ................................................................................................................. 99
CONCLUSIONS ......................................................................................................... 99
REFERENCES ............................................................................................................ 108
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SUMMARY
In parallel with the world wide increase in obesity there has been a dramatic rise in the
prevalence of type 2 diabetes (T2DM) which is associated with a number of micro- and
macro-vascular complications and increases the risk of coronary heart disease. Lifestyle
intervention incorporating a hypocaloric weight loss diet and exercise training is currently
recommended as the cornerstone of diabetes management and has been demonstrated to
improve glycemic control and reduce cardiovascular disease (CVD) risk factors in
individuals with T2DM.
Previous research suggests that manipulating the dietary macronutrient composition may
enhance the weight loss and improve the health status in patients undertaking a
hypocaloric, weight-reducing diet. Within a low fat caloric restricted diet replacing a
portion of carbohydrate with protein has been demonstrated to provide beneficial effects
for weight loss, body composition, and cardiometabolic risk outcomes in overweight and
obese individuals including patients with T2DM. Moreover combining a high protein, low
fat hypocaloric diet with exercise training may provide additive benefits, however the
efficacy of this strategy in patients with T2DM who may achieve the greatest benefits has
been largely unexplored.
The first study in this thesis was a randomised-controlled clinical study which investigated
the effects of a high protein, low fat hypocaloric diet combined with exercise training
compared to an isocaloric high protein, low fat diet without exercise training or an
isocaloric standard protein, low fat diet with or without exercise training on weight loss,
body composition and cardiometabolic risk markers in overweight and obese patients with
T2DM. The results showed that compared to caloric restriction alone participation in
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exercise training during caloric restriction produced greater reductions in body weight and
total body fat mass (FM) and increases in muscular strength. Additionally, replacement of
some carbohydrate with protein further magnified these effects resulting in participants
who consumed the high protein diet and participated in resistance exercise training
experiencing the greatest reductions in weight, total body FM, abdominal FM and insulin
levels. All treatments had similar improvements in glycemic control and CVD risk factors.
These results suggest a lifestyle modification program that combines a calorie restricted
high protein diet and exercise training appears to be a preferred treatment strategy in
overweight/obese patients with T2DM.
A separate line of evidence suggests manipulating the timing of protein intake in relation to
exercise training (consuming protein adjacent to exercise training compared to a delayed
intake) stimulates greater muscle protein synthesis and hypertrophy. This strategy may
therefore promote greater muscle tissue retention and improvements in body composition
during calorie-restricted induced weight loss. This hypothesis was tested in the second
study in this thesis. However, this study showed in overweight and obese patients with
T2DM undertaking a 16 week hypocaloric high protein, low fat diet plus exercise training
lifestyle intervention program, that altering the timing of protein ingestion relative to
exercise (by consuming a 21g protein supplement immediately before exercise compared
to delaying ingestion 2 hours post-exercise) provided no additional benefit to weight loss
and changes in body composition or cardiometabolic risk.
The sustainability of the benefits obtained from intensive short-term research-based
lifestyle intervention programs which incorporate an energy restricted diet and exercise is
often poor, with a rebound frequently occurring following the cessation of the intensive
support. The final study in this thesis followed up participants 1-year after the
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commencement of a 16-week research-based intensive lifestyle (diet and exercise)
intervention program and reported factors identified by those participants as enhancing or
impeding post-intervention program sustainability. Participants identified multiple reasons
for the discontinuation of program components including; a desire for increased diet
variety, a desire for increased portion size, limited access to appropriate exercise programs
and facilities, the cost of gym membership and the withdrawal of professionals to motivate
them. The main factors identified that would have facilitated continuation included having
continued supervision or having to report to someone, having regular recorded weight
checks and diet visits and access to affordable and appropriate exercise facilities.
The findings of this thesis provide information that can be used by health professionals and
policy makers for the development of evidence based recommendations and programs for
the management of T2DM through diet and exercise based lifestyle intervention.
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DECLARATION
This work contains no material which has been accepted for the award of any other degree
or diploma in any university or tertiary institution and, to the best of my knowledge and
belief, contains no material previously published or written by another person, except
where due reference has been made in the text.
I give consent to this copy of my thesis, when deposited in the University Library, being
made available for loan and photocopying, subject to the provisions of the Copyright Act
1968.
I also give permission for the digital version of my thesis to be made available on the web,
via the University’s digital research repository, the Library catalogue, the Australasian
Digital Theses Program and also through web search engines, unless permission has been
granted by the University to restrict access for a period of time.
The author acknowledges that copyright of published works contained within this thesis (as
listed below) resides with the copyright holders of those works
Thomas Philip Wycherley
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Wycherley, T.P., Noakes, M., Clifton, P.M., Cleanthous, X., Keogh, J.B., Brinkworth,
G.D. A high protein diet with resistance exercise improves weight loss and body
composition in overweight and obese patients with type 2 diabetes. Diabetes Care. 2010.
May;33(5):969-976
© 2010 American Diabetes Association
Wycherley, T.P., Noakes, M., Clifton, P.M., Cleanthous, X., Keogh, J.B., Brinkworth,
G.D. Timing of protein ingestion relative to resistance exercise training does not influence
body composition, energy expenditure, glycemic control or cardiometabolic risk factors in
a hypocaloric, high protein, low fat diet in patients with type 2 diabetes. Diabetes Obes
Metab. 2010. Dec;12(12):1097-1105
© 2000-2010 John Wiley & Sons Inc.
Wycherley, T.P., Mohr, P, Noakes, M., Clifton, P.M., Brinkworth, G.D. Self-reported
facilitators of and impediments to maintenance of healthy lifestyle behaviours following a
supervised research-based lifestyle intervention program in patients with type 2 diabetes.
Submitted for Journal Review
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ACKNOWLEDGEMENTS
I would like to thank my primary supervisor Dr. Grant Brinkworth for the countless hours
he has spent mentoring and supporting me throughout my postgraduate studies. Always
approachable, highly knowledgeable and willing to help me to succeed, he has been an
inspiring role model and a great friend.
I would also like to thank my co-supervisor Prof. Peter Clifton for sharing with me his
exceptional scientific knowledge and advice and Assoc. Prof. Manny Noakes for her
guidance and intellect.
My work could never have been completed without the help of the people in the CSIRO
Clinical Research Unit. I gratefully acknowledge; Anne McGuffin for coordinating the
trials; Julia Weaver, Lesley Donnelly and Vanessa Courage for assisting in the study
participant recruitment and scheduling; Xenia Cleanthous, Penelope Taylor and Heidi
Sulda for delivering the dietary interventions; Rosemary McArthur and Lindy Lawson for
providing nursing expertise; Robb Muirhead, Cathryn Seccafien, Vanessa Russell, Candita
Sullivan and Mark Mano for assisting with the biochemical assays; Kylie Lange for
assisting with the statistical analyses and David Jesudason for assisting with the medical
supervision of the participants.
This thesis would not have been possible without the financial assistance of The University
of Adelaide and CSIRO Food and Nutritional Sciences who provided my research
scholarship. Project funding was provided by the National Heart Foundation of Australia,
Diabetes Australia Research Trust and the Pork Cooperative Research Centre. Study foods
were donated by George Weston Foods.
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Finally I would like to thank my family and friends for their support, in particular my
partner Jess for her extraordinary companionship, patience and belief and my parents
Wendy and Allan for providing me with the opportunity and encouragement to pursue my
goals.
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AUTHOR STATEMENTS
Publication 1:
A high protein diet with resistance exercise training improves weight loss and body
composition in overweight and obese patients with type 2 diabetes
Thomas P Wycherley1,2 (BSci (Hons)), Manny Noakes1 (PhD), Peter M Clifton1 (PhD),
Xenia Cleanthous1 (MND), Jennifer B Keogh1 (PhD), Grant D Brinkworth1 (PhD)
1Preventative Health Flagship, Commonwealth Scientific and Industrial Research
Organisation – Food and Nutritional Sciences, Adelaide, Australia
2Department of Physiology, School of Medical Sciences, University of Adelaide, Adelaide,
Australia
The authors’ responsibilities were as follows:
Thomas Wycherley was responsible for the conception and design of the study (including
developing the scientific basis for the research, formulating of the ethics proposal;
identification of outcome testing methodology; development of the exercise training
protocol; establishment of desired macronutrient compositions of the study diets and
relative protein quantities; preparation of data record forms, information and results
sheets), recruitment and screening of the participants, co-coordinated the study
(troubleshoot participant concerns, personal training for exercise groups), performed data
collection (strength assessment, blood pressure assessment, DEXA analysis, auto-analyser
biochemical analysis), managed the study data files, performed data analyses, interpreted
the data and coordinated the writing of the manuscript.
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Manny Noakes contributed to the conception and design of the study, data interpretation
and the writing of the manuscript and designed the experimental diets.
Peter Clifton was responsible for the medical monitoring of the research participants and
contributed to the data interpretation and writing of the manuscript.
Xenia Cleanthous designed the experimental diets, coordinated the implementation of the
dietary protocols and contributed to the writing of the manuscript.
Jennifer Keogh assisted in the design of the experimental diets, contributed to the
conception and design of the study, and contributed to the manuscript.
Grant Brinkworth was responsible for the conception and design of the study, co-
coordinated the study, interpreted the data and coordinated and contributed to the writing
of the manuscript.
All authors agreed on the final version of the manuscript. None of the authors had a
conflict of interest in relation to this manuscript.
Authors Signatures:
I agree with the author contributions for the manuscript “A high protein diet with
resistance exercise training improves weight loss and body composition in overweight and
obese patients with type 2 diabetes”, and give permission for the use of this manuscript in
the thesis.
Thomas Wycherley ……… ……………………………
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Manny Noakes ……… ……….…………..…………………
Peter Clifton ……… ………………………..………………...
Xenia Cleanthous ……… ……………………………..…...
Jennifer Keogh ……… ………………………………….
Grant Brinkworth ……… ………………………..
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Publication 2:
Timing of protein ingestion relative to resistance exercise training does not influence body
composition, energy expenditure, glycemic control or cardiometabolic risk factors in a
hypocaloric, high protein, low fat diet in patients with type 2 diabetes.
Thomas P Wycherley1,2 (BSci (Hons)), Manny Noakes1 (PhD), Peter M Clifton1 (PhD),
Xenia Cleanthous1 (MND), Jennifer B Keogh1 (PhD), Grant D Brinkworth1 (PhD)
1Preventative Health Flagship, Commonwealth Scientific and Industrial Research
Organisation – Food and Nutritional Sciences, Adelaide, Australia
2Department of Physiology, School of Medical Sciences, University of Adelaide, Adelaide,
Australia
The authors’ responsibilities were as follows:
Thomas Wycherley was responsible for the conception and design of the study (including
developing the scientific basis for the research, formulating of the ethics proposal;
identification of outcome testing methodology; development of the exercise training
protocol; establishment of desired macronutrient compositions of the study diets and
relative protein quantities; preparation of data record forms, information and results
sheets), recruitment and screening of the participants, co-coordinated the study
(troubleshoot participant concerns, personal training for exercise groups), performed data
collection (strength assessment, blood pressure assessment, DEXA analysis, resting energy
expenditure analysis, auto-analyser biochemical analysis), managed the study data files,
performed data analyses, interpreted the data and coordinated the writing of the
manuscript.
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Manny Noakes contributed to the conception and design of the study, data interpretation
and the writing of the manuscript and designed the experimental diets.
Peter Clifton was responsible for the medical monitoring of the research participants and
contributed to the data interpretation and writing of the manuscript.
Xenia Cleanthous designed the experimental diets, coordinated the implementation of the
dietary protocols and contributed to the writing of the manuscript.
Jennifer Keogh assisted in the design of the experimental diets and contributed to the
writing of the manuscript.
Grant Brinkworth was responsible for the conception and design of the study, co-
coordinated the study, interpreted the data and coordinated and contributed to the writing
of the manuscript.
All authors agreed on the final version of the manuscript. None of the authors had a
conflict of interest in relation to this manuscript.
Authors Signatures:
I agree with the author contributions for the manuscript “Timing of protein ingestion
relative to resistance exercise training does not influence body composition, energy
expenditure, glycemic control or cardiometabolic risk factors in a hypocaloric, high
protein, low fat diet in patients with type 2 diabetes”, and give permission for the use of
this manuscript in the thesis.
Thomas Wycherley ……… …………………………....
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Manny Noakes ……… ………………………………...……
Peter Clifton ……… ………………………………..………...
Xenia Cleanthous ……… ……………………………..…...
Jennifer Keogh ……… ………………………………….
Grant Brinkworth ……… ………………….…….
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Publication 3:
Self-reported facilitators of and impediments to maintenance of healthy lifestyle
behaviours following a supervised research-based lifestyle intervention program in patients
with type 2 diabetes.
Thomas P Wycherley1,2 (BSci (Hons)), Philip Mohr1 (PhD), Manny Noakes1 (PhD), Peter
M Clifton1 (PhD), Grant D Brinkworth1 (PhD)
1Preventative Health Flagship, Commonwealth Scientific and Industrial Research
Organisation – Food and Nutritional Sciences, Adelaide, Australia
2Department of Physiology, School of Medical Sciences, University of Adelaide, Adelaide,
Australia
The authors’ responsibilities were as follows:
Thomas Wycherley was responsible for the conception and design of the study (including
developing the scientific basis for the research, formulating of the ethics proposal;
preparation of data record forms, information and results sheets), recruitment of the
participants, co-coordinated the study, performed data collection (DEXA analysis),
managed the study data files, performed data analyses, interpreted the data and coordinated
the writing of the manuscript.
Philip Mohr was responsible for the conception and design of the study, interpreted the
data and contributed to the writing of the manuscript
Manny Noakes contributed to the conception and design of the study, data interpretation
and the writing of the manuscript and designed the experimental diets.
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Peter Clifton was responsible for the medical monitoring of the research participants and
contributed to the data interpretation and writing of the manuscript.
Grant Brinkworth was responsible for the conception and design of the study, co-
coordinated the study, interpreted the data and coordinated and contributed to the writing
of the manuscript.
All authors agreed on the final version of the manuscript. None of the authors had a
conflict of interest in relation to this manuscript.
Authors Signatures:
I agree with the author contributions for the manuscript “Self-reported facilitators of and
impediments to maintenance of healthy lifestyle behaviours following a supervised
research-based lifestyle intervention program in patients with type 2 diabetes”, and give
permission for the use of this manuscript in the thesis.
Thomas Wycherley ……… …………………………...
Philip Mohr ……… ……………………………………….
Manny Noakes ……… …………………………...………....
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Peter Clifton ……… …………………………………..…..….
Grant Brinkworth ……… …………………...…...
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PUBLICATIONS ARISING FROM THESIS
Wycherley, T.P., Mohr, P, Noakes, M., Clifton, P.M., Brinkworth, G.D. Self-reported
facilitators of and impediments to maintenance of healthy lifestyle behaviours following a
supervised research-based lifestyle intervention program in patients with type 2 diabetes.
Submitted for Journal Review
Wycherley, T.P., Noakes, M., Clifton, P.M., Cleanthous, X., Keogh, J.B., Brinkworth,
G.D. Timing of protein ingestion relative to resistance exercise training does not influence
body composition, energy expenditure, glycemic control or cardiometabolic risk factors in
a hypocaloric, high protein, low fat diet in patients with type 2 diabetes. Diabetes Obes
Metab. 2010. Dec;12(12):1097-1105
Wycherley, T.P., Noakes, M., Clifton, P.M., Cleanthous, X., Keogh, J.B., Brinkworth,
G.D. A high protein diet with resistance exercise improves weight loss and body
composition in overweight and obese patients with type 2 diabetes. Diabetes Care. 2010.
May;33(5):969-976
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Page xviii
OTHER PUBLICATIONS ARISING DURING CANDIDATURE
Sjoberg, N., Brinkworth, G.D., Wycherley, T.P., Noakes, M., Saint, D.A. Heart rate
variability increases with weight loss in overweight and obese adults with type 2 diabetes.
Submitted for Journal Review
Wycherley, T.P., Brinkworth, G.D., Noakes, M., Keogh, J.B., Buckley, J.D., Clifton, P.M.
Long term effects of weight loss with a very low carbohydrate and high carbohydrate diet
on vascular function in obese subjects. J Int Med. 2010. May;267(5):452-461
Wycherley T.P., Brinkworth G.D., Noakes M., Buckley J.D., Clifton P.M. Effect of caloric
restriction with and without exercise training on oxidative stress and endothelial function
in obese subjects with type 2 diabetes. Diabetes Obes Metab. 2008. Nov;10(11):1062-73
Brinkworth G.D., Wycherley T.P., Noakes M., Clifton P.M. Reductions in blood pressure
following energy restriction for weight loss do not rebound after re-establishment of
energy balance in overweight and obese subjects. Clin Exp Hypertens. 2008.
Jul;30(5):385-96.
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CONFERENCE PRESENTATIONS DURING CANDIDATURE
International
2009 The Obesity Society’s 2009 Annual Scientific Meeting, Tuesday October
27th 2009, Washington DC, USA.
Poster presentation: Caloric restriction with or without resistance exercise
improves emotional distress and quality of life in overweight and obese
patients with type 2 diabetes.
2009 International Diabetes Federation, 20th World Diabetes Congress, Tuesday
October 20th 2009, Montreal, Canada.
Oral presentation: A high protein diet with resistance exercise improves
weight loss and body composition in overweight and obese patients with
type 2 diabetes.
National
2010 Nutrition Society of Australia Annual Scientific Meeting, Wednesday
December 1st 2010, Perth, Western Australia.
Student award: Best oral presentation ($500).
Oral presentation: Timing of protein ingestion relative to resistance
exercise training does not influence body composition, energy expenditure,
glycaemic control or cardiometabolic risk factors in a hypocaloric, high
protein, low fat diet in patients with type 2 diabetes.
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2009 Nutrition Society of Australia Annual Scientific Meeting, Thursday
December 10th 2009, Newcastle, New South Wales.
Oral presentation: A high protein diet with resistance exercise improves
weight loss and body composition in overweight and obese patients with
type 2 diabetes.
2009 Australian Diabetes Society & Australian Diabetes Educators Association
Annual Scientific Meeting, Wednesday August 26th 2009, Adelaide, South
Australia
Oral presentation: A high protein diet with resistance exercise improves
weight loss and body composition in overweight and obese patients with
type 2 diabetes.
2008 Nutrition Society of Australia Annual Scientific Meeting, Monday
December 1st 2008, Glenelg, South Australia.
Oral presentation: Long term effects of weight loss from a very-low-
carbohydrate diet on endothelial function in subjects with abdominal
obesity.
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ABBREVIATIONS
Chapter 1 & Chapter 5
Action for Health in Diabetes (AHEAD)
Australian Diabetes, Obesity and Lifestyle Study (AusDiab)
Body mass index (BMI)
Cardiovascular disease (CVD)
Cardiovascular disease (CVD)
Fat mass (FM)
Fat-free mass (FFM)
Glycosolated Hemoglobin (HbA1c)
Resting energy expenditure (REE)
Type 2 diabetes (T2DM)
Chapter 2
Analysis of variance (ANOVA)
Body mass index (BMI)
Cardiovascular disease (CVD)
Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Dual-energy X-ray absorptiometry (DXA)
Fat-free mass (FFM)
Glycosolated Hemoglobin (A1c)
High protein (HP)
One repetition maximum (1RM)
Resistance exercise training (RT)
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Standard carbohydrate (CON)
Waist circumference (WC)
Chapter 3
Type 2 diabetes (T2DM)
Glycosolated Hemoglobin (HbA1c)
Resistance exercise training (RT)
High protein (HP)
Fat-free mass (FFM)
Resting energy expenditure (REE)
Commonwealth Scientific and Industrial Research Organisation (CSIRO)
One repetition maximum (1RM)
Fat mass (FM)
Computerised homeostatic model assessment – insulin resistance (HOMA2-IR)
Analysis of variance (ANOVA)
Chapter 4
Type 2 diabetes (T2DM)
Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Research-based supervised lifestyle intervention program (RLP)
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CHAPTER 1: RESEARCH BACKGROUND
1.1. Obesity Prevalence
Obesity is now considered a global epidemic. In 2005, the World Health Organisation
estimated that 1.6 billion of the world’s population (age ≥15 years) were overweight (body
mass index [BMI] ≥25 kg/m2) and at least 400 million were obese (BMI ≥30 kg/m2) (1).
The condition continues to rapidly increase in prevalence with conservative estimates
projecting that by 2030, approximately 2.16 billion adults (38% of the worlds population)
and 1.12 billion (20%) will be overweight and obese, respectively (2). This would equate
to an overall global prevalence of overweight and obesity of 3.3 billion people (57.8%), a
44% and 45% increase in overweight and obesity respectively since 2005 (2). In Australia
the prevalence of overweight and obesity is one of the highest in the western world.
Australian data obtained from the ‘2007-08 National Health Survey’ estimated using self-
reported height and weight data, that 37% of adults (≥18 years) were overweight and 25%
were obese (3). Furthermore, although traditionally considered a condition associated with
higher income countries, obesity is now rapidly increasing in low and middle income
countries, particularly in urban areas (1,2).
Obesity is fundamentally caused by a chronic disruption of energy balance in which energy
intake exceeds total energy expenditure (derived from a combination of physical activity,
basal metabolism, and adaptive thermogenesis) (4). Although genetic factors that affect
appetite and metabolism can play a role in determining a person’s susceptibility to obesity,
even with a genetic predisposition obesogenic environmental factors (that promote
excessive calorie intake and discourage physical activity) are usually required for
phenotypic expression (5). Therefore the increase in obesity prevalence can be primarily
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attributed to environmental/lifestyle factors; the World Health Organization have identified
fundamental causes of the obesity epidemic as increased intake of energy-dense foods and
decreased physical activity due to changing modes of transportation, sedentary work
environments and increased urbanization (1,6).
The major concern with obesity is that the condition is associated with a number of
cardiometabolic health consequences including hyperlipidaemia, hypertension and insulin
resistance (7). It is in fact the most critical factor underlying insulin resistance and
therefore plays a major role in the pathogenesis of type 2 diabetes (T2DM) (8,9). Obesity
directly impairs insulin action by up regulating several pathological mechanisms for
insulin resistance that originate in adipocytes (9,10). Adipose tissue modulates metabolism
by releasing free fatty acids and glycerol, hormones and proinflammatory cytokines (9). Of
these, free fatty acids may be the single most critical factor in modulating insulin
sensitivity (9). Free fatty acids are increased in obesity, as a result of increased adipocyte
lipolysis, and induce chronic insulin resistance and impair β-cell function (9,10). The
bodily distribution of adipose tissue also plays an important role in modulating insulin
resistance with central adiposity more strongly associated with insulin resistance than
peripheral adiposity (9,11). Although the precise mechanism/s for this mode of action
is/are not entirely clear, it is possible that intra-abdominal adipocytes are more lipolytically
active and promote greater increases in free fatty acid and free fatty acid flux (rate of
breakdown and uptake) (12). Greater free fatty acid flux appears to be an important factor
in mediating insulin resistance (13) since increasing free fatty acid flux (via a lipid plus
heparin infusion) has been shown to induce insulin resistance in lean individuals (14).
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It is clearly evident that obesity is an enormous global problem underpinning many
cardiometabolic health issues; subsequently it is imperative to develop effective strategies
to combat the growing epidemic.
1.2. Type 2 Diabetes Pathogenesis
T2DM is a metabolic disorder characterised by insulin resistance and/or abnormal insulin
secretion (impaired β-cell function) (10,15-17). T2DM occurs through a continuum of
reductions in tolerance to glucose, beginning with normal glucose tolerance and
progressing through to insulin resistance and compensatory hyperinsulinemia, impaired
glucose tolerance, and eventually T2DM (17).
In individuals with normal glucose tolerance, the relationship between insulin secretion
and insulin action is hyperbolic (Figure 1) (18), meaning β-cells (which produce and
release insulin) respond to a normal change in insulin action by adjusting insulin secretion
to maintain normal glucose tolerance (9,10,17). If progressive increases in insulin
resistance occur (e.g. as a result of obesity), initially there is a chronic compensatory
increase in fasting (2.0-2.5 fold) and glucose stimulated plasma insulin concentrations (17).
Eventually, however, with sustained insulin resistance, β-cells are unable to maintain an
elevated rate of insulin secretion (i.e. β-cell dysfunction occurs) and the fasting insulin
concentration declines precipitously (17). When β-cell function is inadequately low for a
specific degree of insulin sensitivity, deviation from the insulin action, insulin secretion
hyperbola occurs (Figure 1), and glucose tolerance is compromised (e.g. impaired glucose
tolerance and T2DM) (9-11,16). It has been observed that patients with impaired glucose
tolerance have already lost 60-70% of β-cell function (17).
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1.2.1. Figure 1:
β-cells function (insulin release) and insulin sensitivity relationship. T2DM = type 2
diabetes (red), IGT = impaired glucose tolerance (yellow), Normal = normal glucose
tolerance (green). Adapted from Kahn et al. (9).
A number of mechanisms are responsible for the progressive decline in insulin action
and/or sensitivity (Figure 2), and it is well established that these mechanisms which
predispose to T2DM are strongly linked to both genetic and environmental/lifestyle factors
(9,10). The genetic factors underlying T2DM are heterogeneous, with multiple genes
identified that are associated with insulin sensitivity, β-cell dysfunction, and obesity
(including abdominal obesity) predisposition (9,10,19). In particular, the gene PPARG
encoding the hormone nuclear receptor peroxisome proliferator activated receptor , which
regulates fatty acid storage and glucose metabolism, has been implicated in the
NOTE: This figure is included on page 4 of the print copy of the thesis held in the University of Adelaide Library.
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pathogenesis of obesity and T2DM and is the gene variant most commonly associated with
insulin sensitivity (9,20-22).
Despite the role of genetic factors, environmental/lifestyle factors are considered primarily
responsible for the increasing incidence of T2DM (9). As previously mentioned, obesity is
the most critical factor underlying insulin resistance (9), however insulin sensitivity is also
influenced by a number of other non-genetic factors. These include physical activity and
fitness, dietary intake, body fat distribution, ageing (which is associated with a natural
progressive decline in insulin sensitivity (23)) and some medications (corticosteroids,
growth hormone, nicotinic acid) (11). The mechanisms whereby physical activity regulates
insulin sensitivity are less well understood than those previously discussed that relate to
obesity (10). It is postulated that the physical activity specific mechanisms may be
indirectly associated with induced changes in body composition (i.e. reduced fat mass
[FM] and increased lean mass) and/or may be related to adaptations in skeletal muscle fuel
utilisation (24). Compared to individuals with normal glucose tolerance, patients with
T2DM have decreased insulin-stimulated glucose uptake in skeletal muscle (25). Physical
activity is known to up-regulate translocation of insulin stimulated glucose transporter type
4 (GLUT-4) in skeletal muscle from intracellular storage sites to the plasma membrane and
thereby facilitate glucose uptake in muscle tissue (26).
In individuals with normal glucose tolerance, insulin secretion decreases the glucose output
of the liver, increases skeletal muscle glucose uptake and suppresses fatty acid release from
fat tissue (10). Consequently, environmental/lifestyle and genetic factors that lead to
impaired glucose tolerance affect the insulin secretion of the pancreatic β-cells and/or the
action of insulin in fat tissue, skeletal muscle and the liver. This in turn promotes both
hyperglycaemia and increased circulating fatty acids (10). Subsequently, prolonged
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hyperglycemia (glucotoxicity) and chronically elevated free fatty acids (lipotoxicity) can
create a feedback cycle that further worsens insulin action and insulin secretion (Figure 2)
(9,10,16).
1.2.2. Figure 2:
Pathophysiology of hyperglycaemia and increased circulating fatty acids in type 2 diabetes.
Adapted from Stumvoll et al. (10).
1.3. Type 2 Diabetes Diagnosis
The diagnosis for diabetes (both type 1 and 2) is based on glucose criteria as follows (one
or more of)* (27):
1. Glycosolated Hemoglobin (HbA1c) ≥6.5% (USA only)
2. Fasting plasma glucose ≥7.0 mmol.L-1 (no caloric intake for at least 8 hours)
3. 2-hour plasma glucose ≥11.1 mmol.L-1 during a 75 gram oral glucose tolerance test
NOTE: This figure is included on page 6 of the print copy of the thesis held in the University of Adelaide Library.
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4. A random plasma glucose ≥11.1 mmol.L-1 (in a patient with classic symptoms of
hyperglycemia or hyperglycemia crisis)
* Criteria 2 & 4 confirmed by repeat testing in the absence of unequivocal hyperglycemia.
Since hyperglycemia develops gradually, there are individuals whose glucose levels do not
meet the criteria for diabetes but are higher than those considered normal (27). Individuals
in this intermediate stage of diabetes progression (pre-diabetes or impaired glucose
tolerance), whereby either fasting glucose or glucose tolerance are impaired have already
experienced considerable β-cell dysfunction (17) and have a relatively high risk for
developing diabetes in the future (27). Diagnostic criteria for pre-diabetes are as follows:
The diagnosis for pre-diabetes are the presence of one or more of the following (27):
1. Fasting plasma glucose 5.7 mmol.L-1 to 6.9 mmol.L-1 (impaired fasting glucose)
2. 2-hour plasma glucose in the 75 gram oral glucose tolerance test 7.8 mmol.L-1 to 11
mmol.L-1 (impaired glucose tolerance)
3. HbA1c 5.7% to 6.4% (USA only)
N.B. HbA1c is a marker of chronic glycemia, reflecting average blood glucose levels over
a 2- to 3-month time period (27).
1.4. Type 2 Diabetes Prevalence
Due to the fundamental role of obesity in the pathogenesis of insulin resistance it is not
surprising that in sequence with the world wide increase in obesity there has been a parallel
rise in the prevalence of T2DM (which accounts for ~90-95% of all diabetes cases)
(27,28). Approximately 80% of new patients with T2DM are overweight at the time of
diagnosis (6), with most patients being obese (27). Current estimates predict from the years
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2000 to 2030, the total global prevalence of people with diabetes will more than double
from 171 million to 366 million (29).
In particular, data obtained from the ‘1999-2000 Australian Diabetes, Obesity and
Lifestyle Study’ (AusDiab) (30) which used an oral glucose tolerance test to assess fasting
and 2 hour plasma glucose concentrations reported the incidence of T2DM in Australian
adults (≥ 25 years) to be 7.4%. This prevalence has more than doubled since 1981 and is
one of the highest in the western world (31). Half of the participants in the AusDiab study
identified as having diabetes were previously undiagnosed, and a further 16.4% of the
study population had pre diabetes (impaired glucose tolerance or impaired fasting glucose)
(31). More recent data from the ‘2007-08 National Health Survey’ also estimated that 4.0%
of the Australian population reported they had medically diagnosed diabetes mellitus (3).
The increase in T2DM prevalence is attributable to similar environmental/lifestyle factors
to those driving the obesity epidemic (increased intake of energy-dense foods and
decreased physical activity) as well as a contribution due to population growth and an
ageing population (6,9).
1.5. Type 2 Diabetes Consequences and Cost
T2DM is associated with a number of micro- and macro-vascular complications including
hypertension, nephropathy, retinopathy, coronary artery disease, peripheral artery disease
and cerebrovascular disease (32). T2DM increases the risk of coronary heart disease by 2-4
fold (33), with cardiovascular disease (CVD) accounting for 70-80% of death in patients
with T2DM (34). Compared to people without T2DM, patients with T2DM also experience
a higher incidence of other health related impediments including a reduced quality of life
and increased levels of emotional distress (35). In 2005 the total financial cost of diabetes
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in Australia was estimated to be $10.3 billion, including carer costs of $4.4 billion,
productivity losses of $4.1 billion and $1.1 billion in costs to the health system (36).
Prospective studies have identified the degree of glycemia in T2DM as the major
determinant of microvascular complications (37), sensory neuropathy (38), stroke (39),
myocardial infarction (37), diabetes related mortality (37,40) and the prevalence of
reduced quality of life and increased distress (35). It is therefore critically important to
develop strategies to improve glycemic control and this represents the major goal for
reducing the personal burden and financial costs of diabetes and its associated
complications (41).
1.6. Interventional Strategies for Type 2 Diabetes
The current target for patients with T2DM to reduce the risk of micro and macro vascular
disease is to achieve a HbA1c <7% (42). For patients with T2DM a 1% (absolute)
reduction in HbA1c has been associated with a 37% decrease in the risk of microvascular
complications and a 21% decrease in diabetes related mortality (37).
In both the treatment and prevention of T2DM, pharmaceutical agents reduce
hyperglycemia by increasing the action of insulin (e.g. metformin), increasing insulin
secretion (e.g. sulfonylureas), or in later stages of β-cell dysfunction providing an
exogenous source of insulin (10). However, pharmacotherapy also carry high costs and
often unwanted side effects including weight gain (10). Alternatively, lifestyle
modification that incorporates an energy reduced diet and exercise training represents the
cornerstone of T2DM management (43,44). Several studies have demonstrated the benefits
of lifestyle modification for both the prevention of T2DM onset (primary prevention), and
improving weight status, glycemic control and CVD risk factors in patients with T2DM
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(secondary prevention) (45-51). Reductions in total body FM through lifestyle
modification can improve insulin sensitivity, with improvements most strongly related to
reductions in visceral FM (52).
Anderson et al. (51) conducted a meta analysis of 18 studies that assessed lifestyle
modification induced weight loss after 12 weeks in patients with T2DM and found that
weight loss was associated with improvements in blood pressure, the blood lipid profile
and glycemic control.
Data obtained from the ‘Finnish Diabetes Prevention Study’ (49) and the ‘US Diabetes
Prevention Program’ (48) have shown intensive lifestyle intervention that combines diet
and exercise is at least as effective as pharmacotherapy for reducing weight and CVD risk
factors in patients with impaired glucose tolerance. These prospective studies showed a 5-
7% loss of initial body weight achieved through diet and exercise based lifestyle
intervention reduced the incidence of developing T2DM by 58% (48,49).
In further support for the role of lifestyle modification for T2DM management, the long-
term, multi-centre clinical trial ‘Look AHEAD (Action for Health in Diabetes) study’ has
demonstrated that compared to a usual care control condition (involving a program of
diabetes support and education), intensive lifestyle intervention that incorporates an energy
restricted diet and exercise reduced body weight by 8.6% (vs. 0.7%) at 1 year (45) and
4.7% (vs. 1.1%) at 4 years (47,50). In this study, averaged across the 4 years the intensive
lifestyle intervention group had greater improvements than the usual care group in physical
fitness (12.7% metabolic equivalents vs. 2.0% metabolic equivalents), HbA1c (-0.36%
absolute vs. -0.09% absolute), systolic blood pressure (-5.3 mmHg vs. -3.0 mmHg),
diastolic blood pressure (-2.9 mmHg vs. -2.5 mmHg), high density lipoprotein cholesterol
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(0.20 mmol.L-1 vs. 0.11 mmol.L-1) and triglycerides (-1.42 mmol.L-1 vs. -1.10 mmol.L-1).
Although low-density lipoprotein was reduced to a greater extent with usual care (-0.71
mmol.L-1 vs. -0.62 mmol.L-1) this difference was no longer significant after adjusting for
medication usage (-0.51 mmol.L-1 vs. -0.49 mmol.L-1) (47).
Additionally, over the longer-term (>1 year), lifestyle intervention for prevention of T2DM
has shown greater cost effectiveness compared to pharmacotherapy (53). Although the
effectiveness of lifestyle interventions for reducing actual cardiovascular events has yet to
be determined (34); the ‘Look AHEAD study’ currently in progress was designed to
primarily determine whether cardiovascular morbidity and mortality in people with T2DM
can be reduced through intensive lifestyle intervention (54) and on completion (~2014)
should provide this data (47).
1.7. Caloric Restriction for Weight Loss
A moderate hypocaloric diet is a core component of a lifestyle intervention weight loss
program. Over the short-term of a lifestyle intervention weight loss program (incorporating
diet plus exercise) the energy deficit achieved through caloric restriction is usually the
largest contributor to body weight reduction (55). Over the longer term a study by Sacks et
al. (56) also demonstrated that if a reduced calorie diet is sustained (2 years), it is effective
for achieving and maintaining a clinically relevant weight loss (~ -4 kg).
Long-term efficacy studies that have induced chronic caloric restriction via bariatric
surgery have demonstrated significant long-term loss of weight, recovery from T2DM,
improvement in CVD risk factors and reduction in premature mortality (57-59). Adams et
al. (58) matched 7925 participants who underwent bariatric surgery with 7925 participants
in a usual treatment control group (mean follow up duration was 7.1 years). This study
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found that compared to the control group the surgery group had a 40% reduction in
mortality as well as reductions in CVD and T2DM. Sjostrom et al. (59) followed over 4000
obese participants who underwent either bariatric surgery or were prescribed a
conventional treatment (mean follow up duration was 10.9 years). The study found a 24%
reduction in mortality with surgery and after 15 years participant’s weight loss from
baseline was 13-27% for those who underwent surgery (weight changes varied depending
on the type of bariatric procedure used) and 2% for those in the control group. Despite the
apparent success of surgical treatment, lifestyle modification remains the primary
therapeutic approach and bariatric surgery is usually only conducted in severely obese
individuals (BMI ≥ 40 kg.m-2) and usually only as a secondary approach in the event that
lifestyle medication is unsuccessful; but it is not without the risk of death or major
complications (57).
1.8. Fat-Free Mass and Weight Loss
The location and type of tissue loss during weight reduction (i.e. the quality of the weight
loss) is also an important consideration. In terms of tissue location, visceral fat tissue is an
important factor modulating insulin resistance (9,11,12) and reductions in visceral FM, as
opposed to subcutaneous FM are most strongly related to improvements in insulin
sensitivity (52). In regards to tissue type, despite the usual goal of dietary interventions to
achieve weight loss via reductions in FM an accompanying loss of fat-free mass (FFM) is
frequently observed (60) and typically accounts for ~1.2 kg of every 6 kg (20%) of total
weight loss (61). FFM consists of two distinct moieties; highly metabolically active muscle
and organs, and low metabolic rate tissues such as bone and extra cellular mass. (62). FFM
is strongly correlated with resting energy expenditure (REE) (63-65) which is responsible
for approximately 60-70% of daily energy expenditure. REE is commonly reduced with
weight (FFM) loss, whereas maintenance of REE through preservation of FFM maybe
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desirable for minimising the risk of long term weight regain (60). A meta-review showed
that REE was 3-5% lower for formerly obese patients compared to controls, with low REE
likely to contribute to a high rate of weight regain (66). Increased risk of weight gain with
low REE has also been demonstrated in several individual studies (67,68). In addition,
since skeletal muscle represents the largest mass of insulin sensitive tissue (69) further
importance should be placed on the preservation of FFM for patients with T2DM and other
insulin-resistance related metabolic conditions to assist in improving glycemic control
(70).
These important considerations highlight the rationale for developing lifestyle
interventions that target improvements in body composition by enhancing fat and visceral
fat reductions and maintaining/increasing lean muscle mass during weight loss.
1.9. Current Nutrition Recommendations
Based on the data presented in the sections above, it is well established that caloric
restriction is an effective strategy to induce weight loss and formulates a key component of
lifestyle intervention programs. However, the dietary macronutrient profile is also an
important consideration that can potentially play a significant role in modulating weight
loss, weight management and health status (71).
Nutritional macronutrient composition recommendations for patients with T2DM vary
slightly between countries but generally promote an intake of approximately 10-20% of
energy from protein, 45-65% carbohydrate and <35% fat. Specifically, the Diabetes
Australia and the Royal Australian College of General Practitioners ‘Diabetes Management
in General Practice 2010/11’ guidelines (72) specify a diet macronutrient composition for
patients with T2DM of up to 50% of energy from carbohydrate, <30% fat and 10-20%
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protein. Similarly the ‘European Association for the Study of Diabetes’ Diabetes and
Nutrition Study group guidelines (73) specify a diet macronutrient composition of 45-60%
of energy from carbohydrate, <35% from fat and 10-20% from protein. Diabetes UK
provide nutritional recommendations for patients with diabetes (74) that specify a diet
macronutrient composition of 45-60% of energy from carbohydrate, <35% from fat and
recommend ≤1 g.kg-1.day-1 of protein. The Australia and New Zealand ‘Acceptable
Macronutrient Distribution Range’ for lowering chronic disease risk specifies a diet that
consists of 45-65% carbohydrate, 20-35% fat and 15-25% protein (75). The current
American Diabetes Association nutrition guidelines for the management of T2DM
(secondary prevention) do not specify an actual optimal macronutrient profile, but include
the following recommendations (41):
- It is unlikely any one optimal macronutrient profile exists for all patients with
T2DM
- Include carbohydrate from fruits, vegetables, whole grains, legumes, and low-fat
milk, the average minimum requirement for carbohydrate is 130 g.day-1
- Consume a variety of fiber-containing foods to achieve at least the fiber intake
goals set for the general population of 14 g/1,000 kcal; limit saturated fat to <7% of
total energy
- Limit daily alcohol intake to a moderate amount (one drink per day or less for
women and two drinks per day or less for men)
- There is insufficient evidence to suggest that usual protein intake (15–20% of
energy) should be modified and high-protein diets are not recommended as a
method for weight loss at this time.
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The recommended dietary allowance for protein is to consume 0.8 g.kg-1(total body
weight).day-1 of good quality protein (from sources with high protein digestibility corrected
amino acid pattern scores and provide all nine indispensable amino acids e.g. meat,
poultry, fish, eggs, milk, cheese, and soy) (41,75). Since the recommended dietary
allowance assumes a standard body weight, for people who are heavier this body weight
relative recommended dietary allowance does not correspond with the macronutrient ratio
based weight loss diet current dietary recommendations for protein (61,76). For example; a
moderate energy restricted diet (~7000 kJ.day-1) with 10-20% of energy from protein that
provides 41 – 82 g.day-1 maybe inadequate for delivering 0.8 g.kg-1.day-1 of protein for an
overweight/obese patient (>~100 kg), with possible negative implications for body
composition (61,77). In support, Bopp et al. (77) demonstrated an inadequate protein
intake during caloric restriction may be associated with adverse body composition changes.
In a 20-week study in overweight and obese postmenopausal women using a calorie
restricted diet (1420-1670 kJ.day-1 of energy deficit) with a recommended protein
macronutrient content of 15-20% energy (carbohydrate 50-60 %, fat 25-30%), an average
weight loss of 10.8 kg was achieved of which 32% occurred due to reductions in lean
mass. The elevated baseline bodyweight of this group meant absolute protein intake was
only 0.47-0.8 g.kg-1.day-1 (average 0.62 g.kg-1.day-1) and those participants who consumed
higher absolute amounts of dietary protein lost less lean mass, even after adjusting for
body size.
1.10. High Protein, Low Fat Diets
Despite the current nutrition recommendations of leading health authorities an abundance
of scientific debate still exists regarding the optimal macronutrient composition for patients
with T2DM (78). This has largely arisen due to:
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1) Emerging evidence recognising the modification of dietary macronutrient composition
can play a significant role in weight loss, weight management and health status (71).
2) Obese individuals generally experience difficulty in achieving weight loss and body
weight maintenance (71).
3) Observation of an increased popularity and use of alternative dietary patterns (contrary
to current recommendations) that offer hope to individuals seeking effective weight loss
and health improvements (78).
A central focus of the ‘optimal diet macronutrient profile’ debate is the level of dietary
protein and whether altering the macronutrient profile to favour an increased protein intake
(i.e. a ‘high protein diet’) can offer additional benefits (78). Standard protein intake is
12%-18% of total energy whilst a high protein diet is usually considered 25%-35% of total
energy (79) and notably lies outside the Australia and New Zealand ‘Acceptable
Macronutrient Distribution Range’ (75). High protein diets can come in a variety of forms
with the two most prominent categories of high protein diets as follows (79):
1) Replacing a portion of carbohydrate with protein whilst maintaining a low level of fat
(<30%) and saturated fat.
2) Replacing the majority of carbohydrate with protein and fat.
High protein diets may also differ in the method of controlling energy intake and can be
either ‘controlled’, whereby total energy intake, food types and serving sizes are prescribed
to achieve a specific level of caloric restriction and macronutrient profile, or they can be
‘ad libitum’ (usually more applicable to high protein diets that are very low in
carbohydrate) whereby participants follow a set of food intake rules without any particular
prescription of energy intake (e.g. the Atkins diet (80)).
It is difficult to determine the role of protein per se within ‘Atkins style’ very low
carbohydrate diets due to the confounding effect of carbohydrate restriction and a high fat
intake (81). In this thesis a ‘high protein diet’ unless otherwise specified refers to a diet
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that increases protein intake through altering the carbohydrate to protein ratio of a low fat
diet.
1.11. High Protein Diets and Health
A growing body of evidence suggests that during caloric restriction, a high protein diet
compared to a conventional higher carbohydrate diet may provide a number of advantages
(71). Specifically, for overweight and obese subjects including patients with T2DM the
benefits may include attenuating the loss of FFM (61,82,83), attenuating the reduction in
REE (84,85), increasing body fat loss (61,86,87), increasing satiety (82,87), improving an
array of CVD risk factors (insulin sensitivity, glucose homeostasis (84,87) and improving
the blood lipid profile (86-89)). Table 1 provides a summary of the changes in body
weight, FFM and REE from short term (≤4 months) randomised controlled trials which
compare a hypocaloric high protein diet and a standard protein diet. Furthermore, under
weight stable conditions, compared to a usual diet control a eucaloric high protein diet has
also been shown to improve glycemic control in patients with T2DM (90,91), and lower
blood pressure in hypertensive patients (92).
Multiple randomised controlled studies have reported a beneficial effect of an energy
restricted high protein diet compared to an isocaloric standard protein diet for improving
body composition (82,83,86,87,93). Leidy et al. (82) showed during a 12 week hypocaloric
weight loss intervention that a higher protein intake preserves FFM and induced satiety in
pre obese and obese women. This study showed that whilst mean weight loss was ~9 kg in
both groups, FFM was only reduced by 1.5 kg in the high protein diet group (30% protein,
1.4 g.kg-1.day-1) compared to 2.8 kg in the isocaloric control group (18% protein, 0.8 g.kg-
1.day-1). Farnsworth et al. (83) also showed that a high protein diet preserved FFM in
hyperinsulinemic females, but not males, following 12 weeks of energy restriction and 4
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weeks of energy balance. In females, the mean weight loss was 7 kg but FFM was reduced
by -0.1 kg in the high protein diet group (30% protein, ~1.24 g.kg-1.day-1 during weight
loss phase) compared to -1.5 kg in the standard protein group (15% protein, ~0.68 g.kg-
1.day-1). In the males, the overall weight loss was 10.5 kg and FFM reduced similarly in
both groups (high protein diet group 2.5 kg, standard protein diet group 1.9 kg). The exact
reason for the absence of a differential preservation in FFM between the dietary patterns in
the male subjects remains unclear. However, it is noteworthy in this study that due to the
higher baseline body weights of the males, the differential body weight relative protein
contents of the weight loss dietary interventions were markedly less than that of the
females (high protein diet ~1.02 g.kg-1.day-1 vs. standard protein diet ~0.55 g.kg-1.day-1)
and may provide some explanation for the differential gender response. Despite this, the
complete subject cohort (males and females combined) showed the reduction in glycemic
response and triglycerides was greater in the high protein diet group. A separate study also
showed in obese women undergoing caloric restriction that compared to participants
consuming a standard protein diet (18%, ~0.64 g.kg-1.day-1) those with high serum
triacylglycerol (>1.5 mmol.L-1) consuming a isocaloric high protein diet (31%, ~1.12 g.kg-
1.day-1) lost more weight (7.9 vs. 5.8 kg) and FM (6.4 vs. 3.4 kg) and had a greater
decrease in triacylglycerol concentrations (-0.59 vs. -0.03 mmol.L-1) (86). However, no
differences between the diets for participants with serum triacylglycerol ≤1.5 mmol.L-1 or
in the combined whole group analysis were evident, in which the overall weight loss and
reductions in blood lipids, glucose, insulin and lean mass (-1.5 kg on the high protein diet
vs. -1.8 kg on the standard protein diet) were similar. A 12-week weight loss study by
Parker et al. (93) compared a high protein diet (28%, ~1.23 g.kg-1.day-1) with an isocaloric
standard protein diet (16%, ~0.68 g.kg-1.day-1) in overweight or obese patients with T2DM.
Following the intervention there were similar overall reductions in both diet groups for
weight (-4.8 kg on the standard protein diet vs. -5.5 kg on the high protein diet) and lean
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mass (-1.35 kg on the standard protein diet vs. -0.52 kg on the high protein diet), however
females on the high protein diet lost significantly more total (5.3 vs. 2.8 kg) and abdominal
(1.3 vs. 0.7 kg) FM. In a study by Layman et al. (87) although there were no significant
differences between diets in changes in actual body weight, FM or lean mass, they showed
that compared to the energy restricted standard protein diet group (16%, 0.8 g.kg-1.day-1)
participants in the isocaloric high protein diet group (30%, 1.5 g.kg-1.day-1) had an
increased ratio of fat loss to lean loss. Skov et al. (94) examined the effects of replacing
some carbohydrate with protein in a low fat (<30%) diet for 6 months, although the diets
used in the study were consumed ad libitum participants in each group were required to
maintain a specified macronutrient profile and fat intake. Compared to participants who
consumed a high carbohydrate diet (12% protein [70.4 g.day-1], 58% carbohydrate, 30%
fat), participants who consumed a high protein diet (25% protein [107.8 g.day-1], 45%
carbohydrate, 30% fat) lost more total weight (8.7 vs. 5.0kg), FM (7.6 vs. 4.3kg) and intra
abdominal FM (33 vs. 16.8 cm2). In this study it is interesting to note that both groups
achieved weight loss with an ad libitum energy intake which was attributed to the
participants high level of motivation to lose weight. The authors postulated that the
mechanisms responsible for the superior body composition changes with the high protein
diet were a lower reported energy intake in this group (~2 MJ.day-1 difference) and
possibly the greater thermogenic effect of protein.
Although beneficial effects on body composition have not been observed in all individual
studies (95,96) a recent meta-analysis (61) supports the concept that compared with
standard protein diets, high protein diets may provide body composition benefits during
weight reduction. This analysis showed the degree of FFM retention during weight loss
tended to increase with each successive quartile of protein intake (≤0.70 g.kg-1.day-1, >0.70
≤1.05 g.kg-1.day-1, >1.05 ≤1.20 g.kg-1.day-1 and >1.20 g.kg-1.day-1) with significant
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differences between the upper 2 quartiles compared to the lowest quartile. The analysis
identified that protein intakes above 1.05 g.kg-1.day-1 may improve FFM retention during
weight loss induced by caloric restriction.
Previous research has also suggested that REE may also be maintained to a greater extent
with high protein diets (84,85). It is possible this may occur due to several reasons
including an elevated post-prandial increase in energy expenditure (thermogenesis)
associated with increased protein intake, a protein sparing effect on lean mass during
weight loss and/or protein intake influencing hormone levels (e.g. catecholamines and
thyroid hormones) (85). Two small studies showed REE reduced to a lesser extent with a
hypocaloric high-protein diet than with an isocaloric conventional diet (84,85). Whitehead
et al. (85) showed in overweight men and women who underwent a short term caloric
restriction period (7 days, 4200 kJ.day-1) that compared to a diet with a low absolute
protein intake (15% protein [38 g.day-1], 53% carbohydrate, 32% fat), maintaining protein
intake (36% protein [87 g.day-1], 32% carbohydrate, 32% fat) lessened the reduction in 24
hour energy expenditure (-285 kJ.day-1 vs. -541 kJ.day-1) and sleeping energy expenditure
(-207 kJ.day-1 vs. -479 kJ.day-1), despite similar reductions in body weight in both groups
(~-2 kg). Similarly Baba et al. (84) also observed a lesser reduction in REE with a high
protein diet (45% protein [~198 g.day-1], 25% carbohydrate, 30% fat; -553 kJ.day-1)
compared to a high carbohydrate diet (12% protein [~52 g.day-1], 58% carbohydrate, 30%
fat; -1606 kJ.day-1), this occurred despite a greater level of weight loss in the high protein
diet group (-8.3 vs. 6.0 kg). However these effects have not been consistently observed. In
contrast, other slightly longer duration studies (8-12 weeks) have observed similar
reductions in REE following diet induced weight loss irrespective of the level of dietary
protein intake (95,96).
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Macronutrient composition of a hypocaloric diet has also been shown to alter the blood
lipid profile, satiety and glycemic control (87,89,93,97). Layman et al. (87,97) showed that
following ~7.3 kg of weight loss, compared to participants consuming a hypocaloric high
carbohydrate diet, those who consumed a high protein diet had greater levels of satiety
(87), improvements in glucose homeostasis (stabilised blood glucose during nonabsorptive
periods) (97) and reductions in triacylglycerols (87) and the postprandial insulin response
(97). Both diet groups had similar reductions in body weight (~7.3 kg), total cholesterol
(~0.57 mmol.L-1) and low density lipoprotein cholesterol (~0.43 mmol.L-1). Clifton et al.
(89) conducted a pooled data analysis of three weight loss trials (83,86,98) that each
compared a high protein diet (30-40%, 110-136 g.day-1) with a standard protein diet (15-
20%, 60-67 g.day-1). The analysis showed no differences between dietary patterns for
changes in glucose, insulin, total cholesterol, high density lipoprotein cholesterol, low
density lipoprotein cholesterol, total weight loss or body composition, however
triacylglycerol levels decreased to a greater extent with a high protein diet (-0.48 vs. -0.27
mmol.L-1). Post-hoc analysis further revealed that participants with an elevated baseline
triacylglycerol level (>1.54 mmol.L-1) who consumed a high protein diet lost more body
weight (8.5 vs. 6.9 kg) and had greater reductions in FM (-6.17 vs. -4.52 kg), abdominal
FM (-1.92 vs. 1.23 kg), total cholesterol (12 vs. 6%) and triacylglycerol (39 vs. 20%). In
the previously mentioned study by Parker et al. (93) although lipid levels decreased
similarly in both diet groups during the initial 8 week energy restriction phase, following
the 4 weeks of weight maintenance the group consuming the high protein diet pattern
experienced greater reductions in total and low density lipoprotein cholesterol (-0.35 vs. -
0.01 mmol.L-1 and -0.19 vs. 0.09 mmol.L-1 respectively).
Under weight stable conditions, compared to a standard protein diet a eucaloric high
protein diet can also provide beneficial effects for glycemic control and blood pressure
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(90,92). Gannon et al. (90) demonstrated in patients with T2DM that compared to
participants who followed a 5 week standard protein control diet (15% protein, 55%
carbohydrate, 30% fat) those following an isoenergetic high protein diet (30% protein,
40% carbohydrate, 30% fat) had greater decreases in HbA1c (–0.8% vs. -0.3% absolute)
which was attributed to a reduction in the postprandial glucose response (Figure 3).
Hodgson et al. (92) found in hypertensive patients during a randomised controlled trail that
compared to participants who maintained their usual diet (18.6% protein, 31.6% fat)
participants who followed an 8 week eucaloric diet which increased protein content
(+5.3% of energy) at the expense of carbohydrate had lower systolic blood pressure (-5.2
mmHg).
1.11.1. Figure 3:
NOTE: This figure is included on page 22 of the print copy of the thesis held in the University of Adelaide Library.
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Mean (± standard error of the mean) glycosylated hemoglobin (%) during 5 weeks of the
standard protein control (○) or high protein (●) diet. (* P<0.05 significantly different to
standard protein control diet). Adapted from Gannon et al. (90)
To date a limitation of the currently available research is the paucity of long term efficacy
studies (>6 months) investigating the longer term effects of a high protein diet compared to
a normal protein diet (56,99). A two phase study in overweight and obese participants
conducted by Delbridge et al. (99) prescribed either a 12 month high protein diet (30%) or
a normal protein diet (15%) (phase 2) to participants who had completed a 3 month very
low calorie diet period that resulted in 16.5 kg weight loss (phase 1). Following phase 2,
overall weight loss (compared to phase 1 baseline) was similar between the diet groups
(high protein diet -14.8 kg, normal protein diet -14.3 kg), i.e. similar weight regain
occurred in both groups during phase 2 (high protein diet 3.0 kg, normal protein diet 4.3
kg). CVD risk markers also reduced similarly from the phase 1 baseline in both groups,
except for blood pressure which was reduced to a greater extent with the high protein diet.
In this study the dietary compliance data revealed that although protein intakes were
significantly different between the dietary groups and both groups reported similar fat
intakes (~30%), participants in the normal protein group were unable to maintain the
prescribed lower protein intake (15%) and actual reported protein intake was ~22%.
Participants in the high protein diet group reported ~28% which was close to their
prescribed protein intake of 30%. It is therefore possible the smaller differential protein
intakes between the experimental groups may explain the absence of any differential
changes in weight, body composition and CVD risk markers. Moreover, since the
macronutrient manipulation phase of this study was implemented following considerable
weight loss it is unknown whether differential outcomes would have been observed if the
different dietary regimes were implemented from baseline. A separate study by Sacks et al.
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(56) also compared a hypocaloric high protein diet with an isocaloric normal protein diet
over a 2 year period in overweight adults. After the intervention, both diet groups achieved
similar weight loss (normal protein diet -3.6 kg vs. high protein diet -4.5 kg) and reduction
in CVD risk factors, with a trend for a greater reduction in insulin in the high protein diet
group (-10% vs. -4%, P=0.07). However, despite the normal protein diet and high protein
diet participants being prescribed dietary macronutrient percentage intakes
(carbohydrate:protein:fat) of 65:15:20 and 55:25:20 respectively, after 2 years participants
were not able to achieve their target levels with actual macronutrient percentage intakes of
53.2:19.6:26.5 and 51.3:20.8:28.4 respectively. Although the participants who did achieve
the highest protein intake had greater weight loss (within the high protein diet, weight loss
increased with increasing quintiles of protein intake) the overall low compliance with the
treatment assignment limits the understanding of the efficacy of these dietary patterns.
Therefore although these studies suggest no apparent advantage of consuming a long term
high protein diet for weight status or CVD risk factors, further long-term well controlled
studies with careful consideration for maintaining the desired protein intake targets are still
required before any definitive conclusions can be made.
In summary, taken together data from these prior studies suggest replacing some
carbohydrate with protein in a low fat energy restricted diet has at least comparable and in
some instances beneficial effects over the shorter term for reducing triacylglycerol levels,
particularly in patients with elevated baseline levels (81). Additionally, an energy restricted
high protein diet may also provide an advantage over a standard protein diet by increasing
satiety, enhancing weight and FM loss, retaining lean mass, improving insulin regulation
and offsetting diet-induced energy expenditure reductions (71). Under eucaloric
conditions, at least in the short-term, a high protein diet may also decrease blood pressure
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(92) and improve glycemic control (90), although the effects over the longer term remain
largely unknown.
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1.11.2. Table 1:
Summary of short term (≤ 4 months) randomised controlled trials investigating changes in body weight, fat-free mass and resting energy
expenditure following the consumption of a hypocaloric high protein diet (HP) or an isocaloric standard protein diet (SP).
Reference Participants Study Duration Diet Protein Content Weight
Fat-Free Mass
Resting Energy
Expenditure
Leidy et al. (82) Overweight and Obese (46 Females) 12 Weeks
HP 30%, 1.4 g.kg-1.day-1 -8.1 kg -1.5 kg NA
SP 18%, 0.8 g.kg-1.day-1 -9.5 kg -2.8 kg* NA
Farnsworth et al. (83) - Females Only
Hyperinsulinemic (43 Females) 16 Weeks
HP 30%, ~1.24 g.kg-1.day-1 (During 12-week weight loss phase) -6.6 kg -0.1 kg NA
SP 15%, ~0.68 g.kg-1.day-1
(During 12-week weight loss phase) -7.4 kg -1.5 kg* NA
Farnsworth et al. (83) - Males Only
Hyperinsulinemic (14 Males) 16 Weeks
HP 30%, ~1.02 g.kg-1.day-1
(During 12-week weight loss phase) -11.4 kg -2.5 kg NA
SP 15%, ~0.55 g.kg-1.day-1
(During 12-week weight loss phase) -9.6 kg -1.9 kg NA
Parker et al. (93) Type 2 Diabetes (35 Females, 19 Males)
8 Weeks Hypocaloric
4 Weeks Eucaloric
HP 28%, ~1.23 g.kg-1.day-1
(During 8-week weight loss phase) - 5.5 kg -0.5 kg NA
SP 16%, ~0.68 g.kg-1.day-1
(During 8-week weight loss phase) -4.8 kg -1.4 kg NA
Noakes et al. (86) Obese (100 Females) 12 Weeks
HP 31%, ~1.12 g.kg-1.day-1 -7.6kg -1.5 kg NA
SP 18%, ~0.64 g.kg-1.day-1 -6.9 kg -1.8 kg NA
(continued)
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1.11.3. Table 1: Continued
Reference Participants Study Duration Diet Protein Content Weight
Fat-Free Mass
Resting Energy
Expenditure
Noakes et al. (86) - High Triacylglycerol
Obese High Serum Triacylglycerol
(>1.5 mmol.L-1) (50 Females)
12 Weeks HP 31%, ~1.15 g.kg-1.day-1 -7.9 kg -1.5 kg NA
SP 18%, ~0.63 g.kg-1.day-1 -5.8 kg * -2.4 kg NA
Layman et al. (87) Overweight (24 Females) 10 Weeks
HP 30%, 1.5 g.kg-1.day-1 -7.53 kg -0.88 kg NA
SP 16%, 0.8 g.kg-1.day-1 -6.96 kg -1.21 kg NA
Luscombe et al. (95)
Hyperinsulinemic (26 Females, 10 Males)
16 Weeks HP 27%, 1.09 g.kg-1.day-1
(During 12-week weight loss phase) -7.9 kg ~-1.1 kg -650 kJ.day-1
SP 16%, 0.66 g.kg-1.day-1
(During 12-week weight loss phase) -8.0 kg ~-1.2 kg -780 kJ.day-1
Luscombe et al. (96) - Subgroup of Parker
et al. (93)
Type 2 Diabetes
(15 Females, 11 Males)
8 Weeks Hypocaloric
4 Weeks Eucaloric
HP 28%, 1.16 g.kg-1.day-1
(During 8-week weight loss phase) -4.9 kg ~-0.3 kg -109 kJ.day-1
SP 16%, 0.69 g.kg-1.day-1
(During 8-week weight loss phase) -4.3 kg ~-0.3 kg -484 kJ.day-1
Whitehead et al. (85)
Overweight (2 Males, 6 Females)
1 Week HP 36%, 1.07 g.kg-1.day-1 -2.1 kg NA -207 kJ.day-1
SP 15%, 0.47g.kg-1.day-1 -2.3 kg NA -479 kJ.day-1 *
Baba et al. (84)
Hyperinsulinemic (13 Males)
4 Weeks HP 45%, 1.75 g.kg-1.day-1 -8.3 kg NA -553 kJ.day-1
SP 12%, 0.49 g.kg-1.day-1 -6.0 kg * NA -1606 kJ.day-1 *
* Significantly different to HP (P <0.05).
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1.12. Dietary Protein, Body Composition and Muscle Protein Synthesis
It is possible that the effects previously observed for mitigating reductions of FFM during a
hypocaloric high protein diet are mediated by increases in muscle protein synthesis
Previous studies have shown that muscle protein synthesis is increased with the ingestion
of either amino acid mixtures (100) or intact protein (101) although the anabolic effect is
greater with the ingestion of essential amino acids compared to an isocaloric quantity of
intact protein (102). Bohe et al. (103) first demonstrated a dose response relationship exists
between the essential amino acid concentration of the blood and muscle protein synthesis
using amino acid infusion. These researchers showed the concentration of extracellular
essential amino acids rather than that of intramuscular essential amino acids was the
stimulus for muscle protein synthesis. Cuthbertson et al. (100) extended these research
findings demonstrating that ~10g of ingested essential amino acids maximally stimulates
myofibrillar and sarcoplasmic protein synthesis. A muscle protein synthesis response
plateau also appears to follow the ingestion of whole protein with Moore et al. (104)
demonstrating that the muscle protein synthesis response (albeit following exercise
training) was maximally stimulated following the ingestion of 20g of high quality whole
egg protein. Similarly, Symons et al. (105) found 30g of meat protein (113g lean beef)
consumed within a meal, induced the same post-prandial protein synthesis response (~50%
increase in muscle protein synthesis) as a 90g protein serve (340g lean beef).
The mechanism/s whereby dietary protein may enhance body weight and FM reductions
are less well understood; it is plausible that high protein diets have a reduced metabolic
efficiency since protein has a reduced energy efficiency for metabolism compared to an
equivalent caloric intake of fat or carbohydrate (106).
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1.13. Benefits of Physical Activity and Exercise
The other side of the energy balance equation to energy input (caloric intake) is energy
expenditure, of which physical activity or exercise plays a major role (4). For patients with
T2DM it is well recognised the benefits of participation in regular physical activity
independent of weight loss include improved glucose tolerance, increased insulin
sensitivity, decreased HbA1c, improvements in CVD risk factors and improved
psychological well being (107). Therefore, it is not surprising that participation in regular
physical activity is recognised as an important component of current diabetes management
recommendations (108).
Numerous studies have demonstrated the benefits of physical activity or exercise on CVD
risk factors and glycemic control. A Cochrane review meta-analysis on exercise and
T2DM showed that exercise, independent of weight loss, significantly improves glycemic
control and reduces visceral adipose tissue and plasma triglycerides (109). These findings
are consistent with an earlier meta-analysis that showed exercise training independent of
weight loss decreases HbA1c by ~0.66% (absolute) which is an amount that would be
expected to reduce the risk of diabetic complications (110). The ‘Cooper Center
Longitudinal Study’, formally the ‘Aerobics Center Longitudinal Study’ is an ongoing
observational study conducted by the ‘Cooper Institute’ in Dallas, Texas. The study aims
to examine prospectively the relationship of physical activity and physical fitness to health
in patients examined since 1970 (111). Data from a cohort of 25 714 men in this study who
were followed up for approximately 10 years showed low cardiorespiratory fitness
(defined in this study as exercise test maximal metabolic equivalents of: <10.5 for those
aged 20-39 years, <9.9 for those aged 40-49 years, <8.8 for those aged 50-59 years, and
<7.5 for those aged ≥60 years) is a strong independent predictor of CVD and all-cause
mortality in normal weight, overweight and obese individuals (112). Low cardiorespiratory
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fitness’ associated relative risk for CVD death was 3.1, 4.5 and 5.0 for normal-weight,
overweight and obese patients respectively which is comparable to the risk associated with
diabetes mellitus, smoking and several other CVD risk factors (including high cholesterol
& hypertension) (112). In a sub-cohort of men with T2DM from the ‘Cooper Center
Longitudinal Study’, having low cardiorespiratory fitness (defined as being in the least fit
20% of participants) and being physically inactive (participants who did not report
walking, jogging, or participating in aerobic exercise programs in the 3 months prior to
assessment) were also independent predictors of all-cause mortality (relative risk 2.1 and
1.7 respectively) (113). Physical activity has also been shown to play a pivotal role in long-
term weight maintenance. Based on data from the US ‘National Weight Control Registry’
(a pool of over 3000 participants who have maintained at least 30 Lb of weight loss for a
minimum of 1 year), participation in regular physical activity (including programmed
exercise and increased lifestyle activity) has been identified as a key characteristic of these
individuals (114).
1.14. Exercise Training during Weight Loss
Regular exercise plays an important role during caloric restriction by providing additional
benefits compared to caloric restriction alone for weight loss, body composition, CVD risk
reduction and reductions in insulin levels. Several meta analysis reviews and randomised
clinical trials have reported that a combination of a caloric restricted diet plus exercise is
more effective than caloric restriction diet alone for achieving weight loss over the longer
term (55,115,116), improving body composition (117-119) and reducing insulin levels
(118). The most recent meta analysis including 18 long term studies (≥6 months duration)
comparing caloric restriction alone with caloric restriction plus exercise training found that
interventions incorporating caloric restriction plus exercise training resulted in greater long
term weight loss compared to caloric restriction alone (-3.34 vs. -1.38 kg respectively)
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(116). This difference was greater in studies with a duration of ≥1 year compared to those
of a lesser duration. Similar findings were reported in analyses conducted by Miller et al.
(55) and Curioni et al. (115) who also incorporated shorter duration studies (study duration
ranges of 10-52 weeks and 2-90 weeks respectively). Ballor and Poehlman (117)
conducted an earlier meta analysis that used stricter inclusion criteria in order to evaluated
body composition changes achieved through caloric restriction or caloric restriction plus
exercise. In contrast to the prior studies described (55,115,116) this analysis did not find
any differences in the magnitude of body weight reduction between the caloric restriction
alone and the caloric restriction plus exercise training groups. However, compared to
participants who underwent caloric restriction alone, participation in exercise during
caloric restriction reduced the amount of weight loss (by approximately half) that occurred
from reductions in FFM. Similar findings were reported in a randomised clinical trial by
Rice et al. (118) who assigned 29 obese men to 16-weeks of either caloric restriction alone
or caloric restriction plus exercise training. Weight loss (–12.4kg) was similar in all
treatment groups, however FFM was preserved with participation in exercise training and
reduced (–2.5kg) with caloric restriction only. Post-prandial insulin levels also decreased
more with a trend for greater reductions in fasting insulin levels with caloric restriction
plus exercise compared to caloric restriction alone. Finally, participation in regular
physical activity was also the strongest correlate of weight loss after 1-year for participants
in the intensive lifestyle intervention group of the ‘Look AHEAD’ study (120).
1.15. Current Exercise Recommendations
‘Exercise’ is usually categorised as either one or a combination of two main styles; aerobic
or resistance. Aerobic exercise refers to exercise training designed to primarily improve the
efficiency of the cardio-respiratory system; this type of training has consistently been
demonstrated to improve glycemic control, insulin sensitivity and CVD risk factors (121).
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It is currently recommended that patients with T2DM perform moderate intensity aerobic
exercise (50%–80% of VO2 max) for 20-60 continuous minutes per day, 3–7 days per
week or accumulate at least 150 minutes per week of >10 minute bouts of aerobic exercise
(107). The American College of Sports Medicine also recommends patients with T2DM
participate in 2-3 non-consecutive days per week of resistance exercise training which is
exercise training designed to primarily increase strength, power and/or muscular endurance
(107). According to the recommendations resistance exercise training should incorporate
8-10 multi-joint exercises that include all major muscle groups and each individual
exercise should incorporate 2-3 sets of 8-12 repetitions at 60-80% of single repetition
maximum (the heaviest weight that can be lifted once) (107).
Despite the well documented cardiovascular and metabolic health benefits for patients with
T2DM participating in aerobic exercise training either alone or in combination with
resistance exercise training, for several reasons achieving the recommended aerobic
exercise targets is often difficult (122). For example, patients who have been habitually
sedentary, are severely obese, have arthritis, have physical disabilities and/or have diabetes
related complications may find even low level aerobic exercise challenging (121).
Alternatively, resistance exercise represents a relatively safe option for improving
cardiometabolic health and glycemic control even in patients at significant risk of a cardiac
event (123). Research suggests resistance exercise training alone can produce similar
metabolic improvements to that achieved with aerobic exercise and may therefore provide
a beneficial alternative form of physical activity for patients with impediments to aerobic
exercise and those with T2DM (121,122). Resistance exercise training is also relatively
safe with very low myocardial demands associated with even high-intensity resistance
exercise training, equivalent to the occasional actions required in daily living activities
including climbing stairs, walking up a hill or lifting groceries (123).
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1.16. Benefits of Resistance Exercise Training
In patients with T2DM resistance exercise training has been shown to improve glycemic
control (reduce HbA1c), insulin sensitivity, strength and body composition (through
increasing lean tissue mass and promoting total body and abdominal FM loss) and reduce
CVD risk factors (122,124-128). Castaneda et al. (124) demonstrated that compared to a
non-exercise control group, 16 weeks of resistance exercise training (3 days/week)
increased lean mass (1.2 vs. -0.1kg) and reduced HbA1c (-1.1 vs. -0.1%), diabetes
medication (-72 vs. 42%), systolic blood pressure (-9.7 vs. 7.7 mmHg) and trunk fat (-0.7
vs. 0.8 kg). Similarly, in a single-arm, non-controlled trial, Ibanez et al. (125) also showed
a 16 week resistance exercise training program (2 days/week) decreased percent body fat (-
1.3%), abdominal subcutaneous and visceral fat (~11%) and fasting plasma glucose (-0.6
mmol.L-1) and increased upper and lower body strength (10.8 kg [18.1%] and 19.7 kg
[17.1%] respectively). HbA1c levels did not change, but baseline levels were considerably
lower compared to those subjects in the study by Castaneda et al. (124) (6.2 vs. 8.7%), and
were within the recommended range (HbA1c <7% (42)). Several other short term (3-5
month) intervention studies in patients with T2DM and higher baseline HbA1c (7.5-8.8%)
have demonstrated that compared to participants in a non-exercise control group those who
participated in resistance exercise training reduced HbA1c (127,128). Additionally,
strength gains which more often than not occur specifically with resistance exercise
training are also associated with a reduced risk of metabolic disease and all-cause mortality
(129).
1.17. Resistance Exercise Training during Weight Loss
During weight loss there is emerging evidence to support the use of lifestyle intervention
programs that combine caloric restriction with resistance exercise training (60). In patients
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undergoing caloric restriction the addition of resistance exercise has been shown to
enhance FM loss (130), reduce the typical decline or increase FFM (119,131-133), reduce
the typical decline or increase REE (131) and improve strength (131,133). However these
effects have not been consistently demonstrated with other studies reporting no
preservation of FFM (134) or REE (119,132,134) with the addition of resistance exercise
training to caloric restriction.
In a randomised study, Kraemer et al. (119) found in overweight men a 12 week
hypocaloric diet program (~6200 kJ) incorporating both aerobic and resistance exercise
training (3 days.week-1) was superior to caloric restriction alone or caloric restriction plus
aerobic exercise training for improving body composition and strength, although weight
and absolute REE declined similarly in all groups (~ -9.5kg and ~ -380 kJ.day-1). Similar
findings have been reported in obese men and women over 8 weeks by Geliebter et al.
(132) who compared three groups; caloric restriction only (~5400 kJ.day-1), caloric
restriction plus resistance exercise training (3 days.week-1), and caloric restriction plus
aerobic exercise training. Although weight loss was similar in all groups (~9kg) the caloric
restriction plus resistance exercise training group lost significantly less FFM (-1.1 kg)
compared to the caloric restriction plus aerobic exercise training (- 2.3 kg) and the caloric
restriction only (- 2.7 kg) groups; however REE declined similarly in all groups (~ -500
kJ.day-1). Bryner et al. (131) also demonstrated a benefit of resistance exercise training on
body composition during weight loss such that after 12 weeks participants following a
hypocaloric diet plus resistance exercise program lost less lean mass (-0.8 kg) compared to
those who were prescribed a hypocaloric diet plus aerobic exercise training program (-4.1
kg). Participants in the caloric restriction plus resistance exercise program also increased
their maximum strength for the shoulder press, bench press, leg press and leg extension
(≥23%). This study reported contrary findings for REE compared to the findings of
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Kraemer et al. (119) and Geliebter et al. (132) such that although REE decreased in the
caloric restriction plus aerobic exercise training group (-880.7 kJ.day-1) it increased in the
caloric restriction plus resistance exercise group (264.6 kJ.day-1).
Although REE was not measured, Daly et al. (133) conducted a study in patients with
T2DM that compared a 6 month hypocaloric diet consumed either alone or in combination
with a gymnasium based resistance exercise training program. Compared to the caloric
restriction only group, the caloric restriction plus resistance exercise training group tended
to increase lean mass (0.5 kg vs. -0.4 kg) whereas reductions were similar in both groups
for body weight (~3kg) and FM. Upper and lower body muscle strength improved in the
caloric restriction plus resistance exercise training group (43 and 33% respectively) and did
not change in the caloric restriction only group (1.5 and 5.0%, respectively). Over a longer
duration study, Wadden et al (134) compared 48 weeks of caloric restriction alone, caloric
restriction plus resistance exercise training (2 days.week-1), caloric restriction plus aerobic
exercise training and caloric restriction plus a combined aerobic and resistance exercise
training program in obese women. Similar overall reductions occurred for body weight and
REE (-15.1 kg and ~ -670 kJ.day-1) in all groups, however no differences in body
composition were observed between groups which is in contrast to the shorter duration
studies (8-26 weeks) by Kraemer et al. (119), Geliebter et al. (132), Bryner et al. (131) and
Daly et al. (133). It is unclear why the differences in body composition and/or REE are
observed in some studies but not others although it may have something to do with
differences in the duration of the study, the acute resistance exercise program variables
(weight loads, number of repetitions and sets, rest periods etc.) (135,136) and/or the
protein content of the diets (60).
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In further support for resistance exercise training during weight loss it may also provide an
additional benefit for glycemic control in older patients with T2DM. Dunstan et al. (137)
showed that participants who underwent mild caloric restriction (~1400 kJ.day-1) plus
resistance exercise training compared to caloric restriction alone had greater reductions in
HbA1c after 6 months (-1.2% vs. 0.4%) although weight loss was relatively small in both
groups
1.18. High Protein Hypocaloric Diets and Resistance Exercise Training in
Combination
Although prior studies have demonstrated both resistance exercise training and high
protein diets separately, can promote maintenance or increases in REE and FFM during
calorie-restricted weight loss there is growing speculation that consumption of a high
protein diet compared to a standard protein diet may provide additive effects when
combined with high-intensity resistance exercise training for FM loss and the maintenance
of FFM and REE (60,130). To date however there has been limited research investigating
this concept. In 2005, Layman et al. (130) demonstrated that compared to an energy
restricted standard protein diet (18%, 0.66 g.kg-1.day-1) an isocaloric high protein diet
(30%, 1.21 g.kg-1.day-1) combined with exercise training (5 days.week-1 walking and 2
days.week-1 resistance training) additively improved body composition during weight loss
in overweight and obese women such that FM loss was greater in women undertaking
exercise whilst consuming a calorie restricted high protein diet (-8.8 kg) compared to
subjects consuming a caloric restricted high carbohydrate diet with (-5.5 kg) or without (-
5.0 kg) exercise or the consumption of an caloric restricted high protein diet alone (-5.9
kg), indicating an additive effect of a high protein diet and exercise (Figure 4). Moreover,
there was some evidence (P=0.10) that subjects consuming the high protein dietary pattern
lost less lean mass than subjects consuming a high carbohydrate dietary pattern (high
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protein diet alone -2.0 kg and high protein diet with exercise -0.4 kg vs. high carbohydrate
diet alone -2.7 kg and high carbohydrate diet with exercise -2.0 kg) and had greater
reductions in trunk fat (high protein diet alone -3.6 kg and high protein diet with exercise -
5.0 kg vs. high carbohydrate diet alone -3.0 kg and high carbohydrate diet with exercise -
3.2 kg). The blood lipid profile improved in all treatment groups, however participants
consuming the standard protein diet had greater reductions in total cholesterol and low
density lipoprotein cholesterol whereas subjects consuming the high protein diet had
greater reductions in triacylglycerol and maintained higher concentrations of high density
lipoprotein cholesterol.
1.18.1. Figure 4:
Mean (±SEM) changes in percent body fat following 16 weeks of consuming an energy
restricted high protein (PRO) or standard protein (CHO) diet with or without a supervised
NOTE: This figure is included on page 37 of the print copy of the thesis held in the University of Adelaide Library.
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resistance exercise training program (EX). * significant main effect of diet (P<0.05); #
significant main effect of exercise (P<0.05). Adapted from Layman et al. (130).
In overweight or obese men and women undergoing weight loss Arciero et al. (138)
showed that when combined with an exercise training program (incorporating both aerobic
and resistance exercise, 3 days.week-1 of each) a moderate/high protein hypocaloric diet
(~25% of energy) or a high/very high protein diet (~40% of energy intake) elicited similar
reductions in FM and insulin sensitivity and both preserve FFM. However, in both dietary
groups the level of energy restriction was mild (daily energy intake ~7800 kJ) and the
relative protein intakes well exceeded the 1.05 g.kg-1.day-1 reported by Krieger et al. (61)
to promote a beneficial effect on FFM preservation (moderate protein diet 1.21 g.kg-1.day-
1, high protein diet 2.12 g.kg-1.day-1). It is therefore possible that the lack of any differential
effects between the dietary patterns in this study may have been due to the fact that
absolute protein quantity was relatively high in both of the groups and may have provided
a similar maximal stimulus for inducing protein stimulated changes in body composition.
A limitation of this study is that neither of these relatively high absolute protein quantity
lifestyle intervention groups were compared to one with a currently recommended protein
intake (10-20% of energy, 0.8 g.kg-1.day-1). Although, in an earlier study in overweight or
obese men and women (139) this research group showed under ad libitum conditions (that
reported similar energy intakes between the groups ~6700 kJ.day-1) a high protein diet
(40% protein [2.1 g.kg-1.day-1]: 40% carbohydrate: 20% fat) combined with high intensity
exercise training (combined aerobic and resistance exercise) resulted in greater
improvements in strength and had greater reductions in body weight (-5.2 vs. -2.8 kg) total
FM (-5.5 vs. -2.5 kg) and abdominal FM (-0.9 vs. -0.4 kg) compared to a standard protein
diet (50-55% carbohydrate:15-20% protein [1.0 g.kg-1.day-1]: <30% fat) combined with a
moderate intensity exercise program. In this study CVD risk markers (fasting glucose,
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blood lipids and blood pressure) improved similarly, FFM did not change but interestingly
REE increased in both groups.
In a separate 14 week study in sedentary, obese, pre-menopausal women conducted by
Kerksick et al. (140) three energy restricted diets (5000-6700 kJ.day-1) varying in
carbohydrate to protein ratio and each combined with an exercise program (CurvesTM)
were compared for their effects on body composition, REE and CVD risk outcomes. The
study found that a very low carbohydrate, high protein diet (7% carbohydrate, 63% protein
[~1.72-2.30 g.kg-1.day-1], 30% fat), a low-carbohydrate moderate protein (50%
carbohydrate, 20% protein [~0.64-0.86 g.kg-1.day-1], 30% fat), and a high-carbohydrate,
low protein (55% carbohydrate, 15% protein [~0.50-0.68 g.kg-1.day-1], 30% fat) all
similarly reduced body weight, FM, FFM, blood lipids, insulin and glucose. REE
responded differently with the very low carbohydrate, high protein diet (-155 kJ.day-1)
compared to the high-carbohydrate, low protein diet (376 kJ.day-1) and low-carbohydrate
moderate protein diet, 75 kJ.day-1. However, the findings of this study are limited since the
diets were not randomly allocated but rather assigned according to the participant’s
response to a pre-study questionnaire that assessed carbohydrate tolerance and that may
have contributed to baseline differences between the groups in weight, body mass index
and REE.
Meckling and Sherfey (141) also investigated the effect of varying the carbohydrate to
protein ratio (3:1 ‘control diet’ vs. 1:1, ‘high protein diet’) of a hypocaloric diet (-
2180kJ.day-1) either with or without exercise training (circuit training 3 days.week-1) for 12
weeks. Following the intervention, REE, FFM, fasting glucose, insulin and high density
lipoprotein cholesterol did not change in any group; however the high protein diet only
group lost 2.5kg more weight than the control diet only group (-4.6 kg vs. -2.1 kg) and the
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high protein plus exercise group lost 3 kg more than the control plus exercise group (-7.0
kg vs. -4.0 kg). Total cholesterol decreased in the high protein diet only group and the
control diet plus exercise group, low density lipoprotein cholesterol decreased in the high
protein diet only group and triglycerides decreased in the high protein plus exercise group.
However, the interpretation of these results is limited by the poor compliance to the dietary
protein intake targets and subsequent lack of dietary pattern differences in the carbohydrate
to protein ratio between the treatment groups. The diets were planned to achieve a 3:1
(0.75 g.kg-1.day-1) and 1:1 (1.4 g.kg-1.day-1) carbohydrate to protein ratio in the high
protein and control diets respectively, however the actual ratios achieved were dissimilar,
particularly within the high protein dietary pattern (control diet only 3:1 [0.71 g.kg-1.day-1],
control diet plus exercise 2.7:1 [0.74 g.kg-1.day-1], high protein diet only 1.5:1 [1.0 g.kg-
1.day-1] , high protein diet plus exercise 0.96:1 [1.34 g.kg-1.day-1].
It is apparent there remains a paucity of well-controlled studies investigating the effects of
a high protein weight loss diet combined with resistance exercise training compared to
either an isocaloric high protein diet alone or a high carbohydrate diet with or without
resistance exercise training. Furthermore, no studies to date have evaluated these effects in
patients with T2DM who may represent a population with increased dietary protein
requirements (76,142) since T2DM patients have been shown to have increased proteolysis
(potentially reducing net muscle protein balance) under both eucaloric and hypocaloric
conditions that is positively associated with the magnitude of hyperglycemia (142-144). In
addition, as previously mentioned patients with T2DM may achieve additional benefits in
the form of an improvement in glycemic control from the potential preservation of FFM
which may be achieved with a hypocaloric high protein diet plus exercise based lifestyle
intervention. Chapter 2 of this thesis addresses this research need and investigates the
effects in patients with T2DM of a high protein hypocaloric diet combined with resistance
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exercise training compared to isocaloric high protein diet alone or an isocaloric standard
protein diet with or without resistance exercise training on body composition and
cardiometabolic risk markers.
1.19. Timing of Ingestion of Protein Relative to Resistance Exercise on
Muscle Protein Synthesis
Apart from a high protein diet combined with exercise training potentiating the beneficial
effects of a hypocaloric diet, a separate line of evidence suggests that manipulating the
timing of protein intake in relation to resistance exercise training maybe an important
consideration to optimise the outcomes by stimulating greater muscle protein synthesis and
hypertrophy (145).
Muscle protein synthesis is elevated up to 48-hours following resistance exercise training
in untrained participants (146). However, muscle protein synthesis stimulated by elevated
plasma amino acid levels maybe confined to the immediate ~60-120 minutes following
essential amino acid ingestion (147). Further evidence has shown that consuming a protein
source adjacent to exercise (i.e. immediately pre- or post-exercise) increases amino acid
delivery to the muscles and additionally stimulates protein synthesis, providing a
synergistic effect on net protein balance which may offer the greatest anabolic advantage
(148,149).
It has been established that the availability of amino acids rather than energy (in the form
of carbohydrate) is the critical factor for stimulating the post-exercise muscle protein
synthesis, and positive net protein balance, response (150,151). Levenhagen et al. (150)
demonstrated this in an acute feeding study that showed ingestion of a protein rich
supplement (10g protein, 8g carbohydrate, 3g fat) immediately following exercise
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increased whole body protein balance whilst supplementing with either a calorie-free
placebo or an isoenergetic carbohydrate and fat supplement (8g carbohydrate, 3g fat)
resulted in a reduction in whole body protein balance. More recently Tang et al. (151)
demonstrated the acute effect of a high protein meal (10g protein, 21g carbohydrate) is
superior to that of an isocaloric carbohydrate meal (31g carbohydrate) in stimulating
muscle protein synthesis following resistance exercise (151).
Acute feeding studies have shown that compared to a delayed ingestion (≥1 hour) ,
ingesting protein adjacent to exercise training increases muscle protein synthesis and
muscle protein accretion (152-154). The muscle protein synthesis response has been
shown to occur with both amino acid mixtures (153) as well as intact protein (155). Recent
dose response studies have quantified the ingested protein stimulus required to maximise
the post-exercise muscle protein synthesis response; Moore et al. (104) showed in healthy
active males that 20g of intact high-quality protein was sufficient to maximize the anabolic
response to resistance exercise with only a non-significant ~15% further increase in muscle
protein synthesis when the protein dose was doubled to 40g. This was comparable with
earlier research that showed under resting conditions that ~10g of ingested essential amino
acids maximally stimulated myofibrillar and sarcoplasmic protein synthesis (100).
Although it is apparent that acute ingestion of protein adjacent to exercise stimulates
muscle protein synthesis to a greater extent compared to delayed consumption ≥1 hour, it
is not clear whether consumption of a whole protein source either immediately pre exercise
or immediate post exercise (both considered proximal to exercise) offers a superior
response. A study comparing ingestion of protein immediately pre vs. immediately post
exercise showed that net muscle protein balance is greater with immediate pre exercise
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ingestion of crystalline amino acids plus carbohydrate (152). However, in a similar
experimental design, these researchers showed that the anabolic response increased
similarly when actual intact protein was ingested either immediately before or immediately
following resistance exercise training (154). This suggests a pre vs. post advantage may
not exist with the ingestion of intact protein, possibly due to a slower digestion rate (154).
Collectively, these acute studies investigating the muscle protein synthesis response to
protein ingestion and exercise bouts have enabled the identification of optimal protein
doses and timing strategies to maximise the muscle anabolic stimulus. However, whether
this elevated anabolic response directly translates into chronic muscle accretion is more
difficult to determine and has not been conclusively investigated.
1.20. Timing of Ingestion of Protein Relative to Resistance Exercise on
Muscle Accretion under Eucaloric Conditions
A number of studies have extended the findings from the acute muscle protein synthesis
response experiments to assess the chronic effects (8-21 weeks) of ingesting protein
adjacent to resistance exercise training in eucaloric conditions on body composition and/or
muscle hypertrophy (156-162). However, only some (157-160) but not all of these studies
(161,162) have demonstrated a beneficial effect of ingesting protein proximal to exercise
training.
Candow et al. (156) extended the acute findings of Tipton et al. (154) by evaluating the
chronic effects of immediate pre- vs. post exercise protein ingestion. In this study no
differences in body composition were observed between treatment groups when a protein
supplement (~25g) was ingested either immediately pre or immediately post resistance
exercise training (3 days.week-1) for 12 weeks in older men. Esmark et al. (157)
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demonstrated in elderly males that immediate intake of a protein supplement (10g protein,
7g carbohydrate, 3.3g fat) following exercise during a 12 week resistance exercise training
(3 days.week-1) intervention was effective for increasing muscle cross sectional area of the
quadriceps femoris and mean fibre area of the vastus lateralis, compared to no change in
participants who consumed the protein supplement 2 hours post exercise training. However
the differential changes in total body lean mass between the groups (immediate protein
ingestion group +1.8 kg vs. delayed protein ingestion group -1.5 kg) did not reach
statistical significance. Cribb and Hayes (158) showed after 10 weeks that trained
bodybuilders who consumed a protein supplement (1 g.kg-1 of body weight of a
supplement containing 40g protein, 43g carbohydrate, 0.5g fat per 100g) immediately pre-
and post exercise training (4 days.week-1) had greater increases in lean body mass
compared to participants who consumed the supplement in the morning and evening (2.5kg
vs. 1.5kg). However the supplement used in the study also contained 7g of creatine per
100g which may have at least in part affected the outcome. Hulmi et al. (159) randomised
31 young men into 21 weeks of resistance exercise training (2 days.week-1) with either a
15g protein supplement or a non-energetic placebo consumed immediately pre- and post-
exercise. Overall, macronutrient composition of the participant’s diets were similar in both
groups and muscle cross sectional area of the quadriceps femoris increased and body fat
percentage reduced similarly in both groups. However vastus lateralis cross-sectional area
increased to a greater extent with the protein supplementation. The study also found that
immediate ingestion of protein adjacent to exercise training may alter mRNA expression in
a manner advantageous for muscle hypertrophy. Andersen et al. (160) showed that
participants undergoing resistance exercise training (3 days.week-1) for 14 weeks who
ingested protein (25g) immediately pre- and post exercise increased vastus lateralis muscle
fibre cross sectional area whereas those supplementing with carbohydrate (25g) pre- and
post exercise had no change. However, these study results were limited by the lack of any
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dietary records and whether any difference in overall energy intake or the macronutrient
profiles between the treatment groups contributed to the observed effects could not be
determined.
In contrast, other studies have reported no additional benefit for promoting muscle
accretion by ingesting protein proximal to exercise training. Hoffman et al. (162) compared
resistance exercise trained males following 10 weeks of resistance exercise training (4
days.week-1) with a protein supplement (42g protein, 2g carbohydrate, 0g fat) ingested
either in the morning and afternoon or immediately pre- and post exercise training.
Following the intervention, no differences between the groups for changes in body
composition were observed. However, it is possible that the lack of any group differences
could have been caused by the high relative protein intakes achieved in the study (~2.2
g.kg-1.day-1) that may have masked any additional benefit from supplement timing (163).
Burk et al. (161) in an 8 week cross over study design compared participants consuming a
protein supplement (35g protein, 0.4g carbohydrate, 0.1g fat) 4-6 hours pre exercise
training (4 days.week-1) and immediately prior to exercise to when participants consumed
the supplement 4-6 hours pre exercise training and 2.5 hours following dinner (exercise
training was conducted at 4pm). In contrast to the findings of Cribb and Hayes (158) the
post dinner supplement group increased FFM (1.1 kg) whereas FFM in the pre exercise
supplement group did not change. The authors speculated a potential explanation for the
difference between the treatment groups was that the post dinner supplement group
experienced greater daily distribution of their protein allocation which may have prolonged
the duration of amino acidemia (and hence the chronic anabolic response) and therefore
over several weeks this may have lead to an increased protein deposition (FFM). This
theory supports observations from a study by Moore et al. (104) that showed an acute
anabolic response to protein ingestion can potentially be achieved up to 5-6 times per day,
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which may possibly negate any additional synergistic effect of superimposing resistance
exercise training and amino acid/protein ingestion on net protein balance (148,149). It was
further speculated that these results may have contrasted those of Cribb and Hayes (158)
due to differences in duration of training and the type of supplement used (protein
composition, carbohydrate content and creatine vs. no creatine). Additionally, as was the
case in the study by Hoffman et al. (162) in this study the relative protein intake of both
diets was very high (~2.2 g.kg-1.day-1) and therefore both dietary patterns may have
provided a maximal stimulus.
1.21. Timing of Ingestion of Protein Relative to Resistance Exercise on
Muscle Accretion under Hypocaloric Conditions
Although multiple studies have evaluated the acute and chronic effects of manipulating the
timing of protein ingestion relative to the performance of exercise training on body
composition changes under eucaloric conditions, there remains a paucity of data examining
whether consuming protein proximal to exercise training provides an advantage for
ameliorating FFM loss during calorie-restricted induced weight loss (61).
To date, only one known study has chronically examined the effects of manipulating the
timing of protein ingestion relative to resistance exercise training during caloric restricted
induced weight loss (164). Doi et al. (164) showed that after a 12-week hypocaloric diet
plus resistance exercise training intervention FFM did not decrease and resting metabolic
rate significantly increased in subjects who consumed a protein supplement immediately
following resistance exercise. Despite daily energy and protein intake being similar in both
groups, in subjects who did not receive the supplement FFM significantly decreased and
REE remained unchanged. This study suggests that protein ingested in close proximity to
exercise may be associated with increased total body protein synthesis that may offset
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reductions in FFM and REE that typically occur with weight loss. However, this study was
performed in young healthy men with relatively normal body weight and levels of
adiposity and the degree of energy restriction was only mild (15% deficit). The findings of
this study were also limited by the statistical analyses performed in which the conclusion
was based on single-arm within group comparisons, using separate within group paired t-
tests to compare pre- and post- values rather than by direct between-group comparisons. In
fact, no significant differences were observed when direct between-group comparisons
were made between the men who ingested a protein supplement proximal to exercise and
those who did not (control) with a comparable reduction in FFM between groups (-1.8 kg
vs. -2.1 kg respectively).
Further research is required to establish the effect of altering the timing of protein ingestion
relative to exercise training. Specifically, it is particularly relevant to establish these effects
in overweight and obese patients with established metabolic disease such as patients with
T2DM who may obtain multiple benefits from strategies that assist in preserving FFM
during weight loss by way of facilitating long term weight loss maintenance and improved
glycemic control. The experiment described in Chapter 3 of this thesis investigates whether
in overweight and obese patients with T2DM any additional potential benefit of a high
protein diet combined with resistance exercise training on body composition, REE,
glycemic control or cardiometabolic risk factors could be further magnified by
manipulating the timing of protein ingestion relative to resistance exercise training.
1.22. Barriers to Healthy Lifestyle Behaviours
As previously discussed, intensive lifestyle intervention programs incorporating an energy
restricted diet and exercise training are effective for inducing improvements in weight
status and metabolic control (45,46,48,49). However, long-term sustainability of these
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benefits is often poor with rebound frequently occurring after the intensive support of the
program is ceased, even when multiple behavioural change strategies are used
(133,165,166). From a social ecological model perspective barriers and facilitators for
healthy lifestyle behaviours occur at several levels ranging from intrapersonal skills and
choices (e.g. knowledge) to external factors including immediate intrapersonal support
(e.g. family and peers), community factors (e.g. food availability, workplace culture) and
public policy (e.g. advertising and laws) (167-169). The external factors are of particular
importance as although acquiring knowledge enables patients to make informed decisions,
the motivation to act is determined by a combination of many additional factors including
the ability to adapt to diabetes related stresses, the interpersonal style of the health
professional and target setting (170-172). Ultimately, to achieve successful maintenance of
weight status and metabolic control, patients are required to establish ongoing healthy
lifestyle behaviours. Several key healthy lifestyle behaviours have been identified in
individuals that have been successful at maintaining long-term weight loss including the
participation in regular physical activity and frequent monitoring of body weight,
food/calorie intake and fat intake (114,120,173).
For patients with T2DM, the greatest difficulties for the management of their condition
relate to adhering to diet and exercise recommendations with fewer barriers associated with
blood glucose monitoring and medication use (174-176). Within the context of diet and
exercise a limited number of studies have identified several reasons why people with
T2DM do not participate in healthy lifestyle behaviours. For diet, these include the cost,
difficulties adhering to portion sizes, support and family issues and quality of life and
lifestyle issues (177). For exercise the reasons include difficulty participating, feelings of
tiredness, being distracted by something else, a lack of time, a lack of facilities, fear of
injury, low self-efficacy in respect of a novel or unfamiliar exercise mode and the
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assumption that exercise will lead to increased muscle mass and therefore weight gain
(178,179). However, as opposed to factors which prevent change and initial participation
in healthy diet and exercise lifestyle behaviours little is known about specific factors that
assist or impede people in continuing with healthy lifestyle (diet and exercise) behaviours
once established (e.g. through participation in a structured intensive lifestyle intervention
program). Currently, only one known study in hypertensive patients has evaluated the
dietary factors (180) and one study in patients with T2DM has examined the exercise
specific factors (181).
1.23. Barriers and Facilitators for Adherence to a Diet
To understand the specific factors that underlie dietary adherence Vijan et al. (177)
investigated barriers to following dietary recommendations in patients with T2DM using a
written random postal survey and a mix of urban and suburban focus groups. The results
showed that following a moderate diet intervention (sugar and fat reduced with minimal
caloric restriction) was more of a burden than taking oral agents but substantially less of a
burden than insulin injections. However, a strict diet (sugar and fat reduced plus caloric
restriction for weight loss) had a similar burden to taking insulin. Interestingly, patients
with T2DM were less likely to adhere to following a moderate diet than to taking oral
agents or insulin, despite the higher associated burden. The most commonly identified
barrier to following a diet were costs, limited portion size and subsequent hunger, a lack of
family support, confusion about the diet prescription, difficulty adhering during
holidays/social occasions, emotional aspects of having to follow the diet, a dislike of
specific dietary foods and difficulties with the eating schedule.
Jehn et al. (180) also identified similar themes following an investigation of factors that
affect continuation of a healthy diet once initiated. This study was a 1 year follow up of
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hypertensive patients who had participated in either a 9 week diet and exercise weight loss
intervention or a control group. Despite an initial 5.3 kg weight loss in the intervention
group, after 1 year post-intervention, participants had regained the majority of their weight
loss (-0.5 kg from baseline) whilst participants in the control group had increased their
weight slightly (0.9 kg from baseline). The participants identified several self reported
barriers to maintaining weight loss including (in order of the number of times they were
identified) losing trial structure, an inability to estimate the appropriate portion size, an
inability to calculate caloric needs, the recommended diet was too expensive, lack of time
to follow the diet, weight loss was not a priority and lack of support from family and
friends. But although this study evaluated post-intervention barriers, the interpretability of
the findings to patients with T2DM undertaking a holistic lifestyle program are limited
since the study was conducted in a non-diabetic population and isolated to an evaluation of
dietary factors.
1.24. Barriers and Facilitators to an Exercise Program
Similar to the dietary component of lifestyle interventions, sustainability of exercise is
often associated with limited success. Kirk et al. (182) conducted a review on strategies to
enhance compliance to physical activity recommendations in patients with insulin
resistance. It was determined that long term change is difficult to achieve and the limited
research available suggests the core components for sustainability are the development of
cognitive behaviour skills, follow-up support and an individualised approach.
The previously described study by Daly et al. (133) that included a 6 month caloric
restriction program either alone or combined with a gymnasium based resistance exercise
training program, also included a second phase consisting of a one month transition period
into a 6 month home-based resistance exercise training program. The objective was to
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examine whether any of the initial benefits achieved in phase 1 could be maintained
through a subsequent home-based program. During the home based exercise phase,
compliance reduced and FM was regained to baseline levels suggesting that even with a
transitionary approach towards a prescribed home based program (that included regular
phone contact), without personal support structured exercise training may be difficult to
achieve.
Thomas et al. (178) used questionnaires distributed at a diabetes clinic to investigate the
self perceived factors that prevent patients with diabetes from commencing participation in
physical activity. Lack of local facilities, the cost of accessing exercise facilities and a lack
of time were identified as the main deterrents. Only one known study to date has reported
the self-identified factors that either assist or impede patients with T2DM in continuing a
structured exercise program following the completion of an intensive lifestyle intervention
program. In that study, Casey et al. (181) conducted a qualitative analysis of the barriers
and facilitators to the continuation of exercise following participation in a structured
aerobic exercise training program in overweight and obese individuals with T2DM. The
key factors identified by the participants for sustaining the exercise were motivation from
monitoring, encouragement and accountability provided by the programme staff and to a
lesser extent effective transition from supervised programmes to self-directed activities.
However, the results of this study are somewhat limited since the lifestyle intervention
program used in the study did not incorporate an energy restricted diet; and the exercise
program was limited to aerobic exercise which may present different sustainability
challenges to those of a resistance exercise training program.
1.25. Barriers and Facilitators to Continuing an Established Diet and
Exercise Based Lifestyle Intervention Program
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To date, no studies have evaluated the barriers and facilitators to the continuation of
established holistic healthy lifestyle practices (incorporating both diet and exercise) that
have been acquired through prior participation in an intensive weight loss program.
Healthy lifestyle practices are of particular importance to overweight and obese patients
with T2DM who have the additional concerns of glycemic control as well as the potential
additional burden of hypoglycemic medication and diabetes complications. This
information would provide a valuable insight to the concerns of patients with T2DM and
assist in identifying critical areas to target for support and policy that can be used in turn to
achieve long term improvements in the weight and health status of patients with T2DM.
Chapter 4 of this thesis investigates the factors perceived by individuals’ with T2DM that
enhance or impede the sustainability of acquired healthy lifestyle behaviours, previously
obtained through participation in a research based lifestyle intervention program that
achieved considerable weight loss and improvements in glycemic control and CVD risk
factors.
1.26. Specific Aims of this Thesis
The aim of this thesis was to evaluate the efficacy of lifestyle intervention weight loss
programs that incorporate a high protein diet and exercise training in overweight and obese
patients with T2DM and indentify factors that facilitate or impede their long-term
sustainability and success by:
1. Comparing a hypocaloric high protein diet with an isocaloric standard protein diet, with
or without exercise training on body composition and cardio metabolic outcomes in
overweight and obese patients with T2DM.
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2. Investigating within a hypocaloric high protein diet plus exercise training whether
manipulating the timing of protein intake in relation to exercise training (consuming
protein adjacent to exercise training vs. a delayed intake) can provide any additional
benefit on the measured outcomes.
3. Conducting a long-term, follow-up exploratory qualitative analysis of participants to
identify self perceived barriers and facilitators to sustaining developed healthy lifestyle
behaviours in a community setting following participation in a research based lifestyle
intervention program that achieved considerable weight loss and improvements in
glycemic control and CVD risk factors.
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CHAPTER 2: A HIGH PROTEIN DIET WITH RESISTANCE EXERCISE TRAINING IMPROVES WEIGHT LOSS AND BODY COMPOSITION IN OVERWEIGHT AND OBESE PATIENTS WITH TYPE 2 DIABETES
Thomas P Wycherley1,2, Manny Noakes1, Peter M Clifton1, Xenia Cleanthous1, Jennifer B
Keogh1, Grant D Brinkworth1
1Preventative Health Flagship, Commonwealth Scientific and Industrial Research
Organisation – Food and Nutritional Sciences, Adelaide, Australia
2Department of Physiology, School of Medical Sciences, University of Adelaide, Adelaide,
Australia
Diabetes Care. 2010. May;33(5):969-976
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2.1. Summary
The aim of this chapter was to compare the effects of an energy restricted high protein diet
and an isocaloric standard protein diet with and without resistance exercise training on
weight loss, body composition, CVD risk factors and glycemic control in overweight/obese
patients with T2DM.
The results showed that participation in resistance exercise training produced greater
weight and FM loss and increases in muscular strength compared to caloric restriction
alone. Additionally, replacement of some carbohydrate for protein further magnified these
effects resulting in this group achieving the greatest reductions in weight, total body FM,
abdominal FM and fasting insulin. All treatments had similar improvements in glycemic
control and CVD risk factors.
The findings of this chapter suggest a lifestyle modification program combining a calorie
restricted high protein diet and resistance exercise training appears to be a preferred
treatment strategy in overweight/obese individuals with T2DM.
Page 82
Wycherley, T.P., Noakes, M., Clifton, P.M., Cleanhous, X., Keogh, J.B. and Brinkworth, G.D. (2010) A High-Protein Diet With Resistance Exercise Training Improves Weight Loss and Body Composition in Overweight and Obese Patients With Type 2 Diabetes. Diabetes Care, v. 33 (5), pp. 969-976, May 2010
NOTE: This publication is included on pages 54 – 63 in the print
copy of the thesis held in the University of Adelaide Library.
It is also available online to authorised users at:
http://dx.doi.org/10.2337/dc09-1974
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CHAPTER 3: TIMING OF PROTEIN INGESTION RELATIVE TO RESISTANCE EXERCISE TRAINING DOES NOT INFLUENCE BODY COMPOSITION, ENERGY EXPENDITURE, GLYCEMIC CONTROL OR CARDIOMETABOLIC RISK FACTORS IN A HYPOCALORIC, HIGH PROTEIN, LOW FAT DIET IN PATIENTS WITH TYPE 2 DIABETES
Thomas P Wycherley1,2, Manny Noakes1, Peter M Clifton1, Xenia Cleanthous1, Jennifer B
Keogh1, Grant D Brinkworth1
1Preventative Health Flagship, Commonwealth Scientific and Industrial Research
Organisation – Food and Nutritional Sciences, Adelaide, Australia
2Department of Physiology, School of Medical Sciences, University of Adelaide, Adelaide,
Australia
Diabetes, Obesity and Metabolism. 2010. Dec;12(12):1097-1105
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3.1. Summary
The results of the Chapter 2 study showed in overweight and obese patients with T2DM an
energy restricted high protein diet plus resistance exercise training induced clinically
relevant greater reductions in body weight and FM compared with either an isocaloric high
protein diet alone or a standard protein diet alone or combined with exercise training. The
aim of Chapter 3 was to investigate whether additional benefits could be achieved in this
‘superior’ high protein diet plus exercise training lifestyle intervention program by
manipulating the timing of ingestion of protein relative to exercise training.
The results showed that in overweight and obese patients with T2DM who were
undertaking a hypocaloric high protein diet plus exercise training lifestyle intervention
program altering the timing of protein ingestion relative to exercise by consuming a
supplement containing 21g of protein immediately before exercise compared to delaying
ingestion 2 hours post-exercise has no additional benefit. Both groups achieved substantial
weight loss, improvements in strength and glycemic control, and had similar reductions in
cardiometabolic risk factors, FFM and REE.
The findings from this chapter re-affirm that for overweight and obese individuals with
T2DM participation in a lifestyle modification program combining an energy restricted
high protein diet plus resistance exercise training is an effective treatment strategy for
reducing body mass and cardiometabolic risk factors and improving glycemic control and
muscular strength. However, within this lifestyle intervention program altering the timing
of protein ingestion relative to exercise training appears to provide no additional benefit on
these outcomes or the attenuation of FFM reductions.
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Wycherley, T.P., Noakes, M., Clifton, P.M., Cleanhous, X., Keogh, J.B. and Brinkworth, G.D. (2010) Timing of protein ingestion relative to resistance exercise training does not influence body composition, energy expenditure, glycaemic control or cardiometabolic risk factors in a hypocaloric, high protein diet in patients with type 2 diabetes. Diabetes, Obesity and Metabolism,v. 12 (12), pp. 1097-1105, December 2010
NOTE: This publication is included on pages 64 – 74 in the print
copy of the thesis held in the University of Adelaide Library.
It is also available online to authorised users at:
http://dx.doi.org/10.1111/j.1463-1326.2010.01307.x
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CHAPTER 4: SELF-REPORTED FACILITATORS OF AND IMPEDIMENTS TO MAINTENANCE OF HEALTHY LIFESTYLE BEHAVIOURS FOLLOWING A SUPERVISED RESEARCH-BASED LIFESTYLE INTERVENTION PROGRAM IN PATIENTS WITH TYPE 2 DIABETES
Thomas P Wycherley1,2, Philip Mohr1, Manny Noakes1, Peter M Clifton1, Grant D
Brinkworth1
1 Preventative Health Flagship, Commonwealth Scientific and Industrial Research
Organisation – Food and Nutritional Sciences, Adelaide, Australia
2 Department of Physiology, School of Medical Sciences, University of Adelaide,
Adelaide, Australia
Submitted for Journal Review
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4.1. Summary
Chapters 2 and 3 of this thesis demonstrated that a short term (16-week) lifestyle
intervention program that incorporated caloric restriction with or without exercise training
was effective for reducing body weight and a number of cardiometabolic risk markers. In
Chapter 4 the participants who completed the lifestyle intervention programs (described in
Chapters 2 & 3) were followed-up one year following the program commencement (36
weeks following program completion). The aim of this study was to identify through a
qualitative interview the factors identified by participants as enhancing or impeding the
sustainability of lifestyle behaviours adopted throughout the research based lifestyle
intervention program.
The results showed that on average participants who attended the follow-up regained some
of the body weight lost during the intervention program but still weighed considerably less
than baseline. Only a small number of the participants were still maintaining the program
in its entirety. Participants identified a number of reasons for the discontinuation of
program components including; a desire for increased diet variety, a desire for increased
portion size, limited access to appropriate exercise programs and facilities, the high price
of gym membership and no longer having a professional to motivate them. The main
factors identified that would have facilitated continuation included having continued
supervision or having to report to someone, having regular recorded weight checks and diet
visits and having access to affordable and appropriate exercise facilities.
The results suggested that in overweight and obese individuals with T2DM the initial
success of the lifestyle intervention program was perceived as being primarily due to high
levels of professional support and supervision, the discontinuation of which subsequently
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presented difficulties. The interview data remind us that intensive programs assembled for
research purposes with the emphasis on compliance may not be a realistic model for
community intervention.
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4.2. Publication 3
Self-reported facilitators of and impediments to maintenance of healthy lifestyle
behaviours following a supervised research-based lifestyle intervention program in
patients with type 2 diabetes
Wycherley, TP1, 2, Mohr, P1, Noakes, M1, Clifton, PM1, Brinkworth, GD1
1 Preventative Health Flagship, Commonwealth Scientific and Industrial Research
Organisation – Food and Nutritional Sciences, Adelaide, Australia
2 Department of Physiology, School of Medical Sciences, University of Adelaide,
Adelaide, Australia
Address correspondence to Dr. Grant D Brinkworth, CSIRO - Food and Nutritional
Sciences, PO Box 10041 BC, Adelaide, South Australia 5000. Tel: +61 8 8303 8830. Fax:
+61 8 8303 8899. Email: [email protected]
Word Count: 4252 (main text), 232 (abstract)
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4.2.1. ABSTRACT
Introduction: Sustainability of healthy lifestyle behaviours following participation in a
research-based supervised lifestyle intervention program (RLP) is often poor. This study
aimed to document factors reported by overweight and obese individuals with type 2
diabetes (T2DM) as enhancing or impeding sustainability of lifestyle behaviours following
participation in a RLP.
Methods: 30 patients who completed a 16-week RLP, incorporating a structured energy
restricted diet with or without supervised resistance exercise training underwent a semi-
structured qualitative interview about their experiences in maintaining program
components after 1 year.
Results: Participants maintained 8.8±8.9kg of the 13.9±6.6kg weight loss achieved with
RLP. Only 23% of participants indicated continuation of the complete diet program. Desire
for ‘variety’ (33%) and increased portion size (27%) were the most commonly reported
reasons for discontinuation. Participants who undertook supervised exercise training during
the RLP indicated access to appropriate programs/facilities (38%), more affordable gym
membership (21%) and having a personal trainer/motivator (17%) would have facilitated
exercise continuation.
Conclusion: In overweight and obese individuals with T2DM, success of RLP was
perceived as being primarily due to high levels of professional support and supervision, the
discontinuation of which subsequently presented difficulties. The interview data provide
insight into what people experience in the outside world without intensive support of the
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research setting and remind us that intensive programs assembled for research purposes
with the emphasis on compliance may not be a realistic model for community intervention.
Key Words: Obesity, Nutrition
Abbreviations:
Commonwealth Scientific and Industrial Research Organisation = CSIRO
Research-based supervised lifestyle intervention program = RLP
Type 2 diabetes = T2DM
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4.2.2. INTRODUCTION:
Overweight and obesity are closely linked to the development of type 2 diabetes
(T2DM)[1]. Lifestyle modification that combines an energy reduced diet and regular
physical activity formulates the cornerstone for obesity and T2DM management [2]. It has
been repeatedly demonstrated that research-based supervised lifestyle intervention
programs (RLP) incorporating these components promote weight loss, decrease
cardiovascular disease risk factors and improve glycemic control, body composition and
health related quality of life in overweight and obese patients with T2DM [1, 3-6].
However, long-term sustainability of these healthy lifestyle behaviours, weight
maintenance and improved metabolic control following participation in a RLP is often
poor without continued support, with a rebound in these outcomes frequently occurring
after completion [7, 8].
To date, only one known study in T2DM has examined individuals’ perceptions of factors
that assist or impede them in continuing with a lifestyle intervention program following
completion of a RLP [9]. In that study, Casey et al. [9] conducted a qualitative analysis of
the barriers and facilitators to the continuation of exercise following participation in a
structured aerobic exercise training program in overweight and obese T2DM individuals.
Motivation from monitoring, encouragement and accountability provided by the
programme staff and, to a lesser extent, effective transition from supervised programmes to
self-directed activities, were identified as key factors by participants for sustaining the
exercise over the long-term following the initial program. However, the RLP used in this
study did not incorporate an energy restricted diet, a core component of comprehensive
T2DM lifestyle modification [2]. Additionally, the exercise program was limited to
aerobic-based exercise; whereas resistance exercise, which is well recognised as an
important exercise therapy for T2DM [10], may present different sustainability challenges.
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The objective of the present study was to identify factors reported by participants as
enhancing or impeding the sustainability of lifestyle behaviours in overweight individuals
with T2DM following completion of a RLP incorporating an energy restricted diet with or
without a resistance-based exercise program.
4.2.3. METHODS:
This study was conducted as a 1-year follow-up after the commencement of a 16-week
RLP incorporating a structured energy restricted diet with or without supervised resistance
exercise training in which participants had initially volunteered. The RLP has been
described in detail elsewhere [11] and was designed to achieve maximal compliance to
assess the efficacy of the specific lifestyle therapies being evaluated. . Briefly the
structured diet was a moderately energy restricted (females; ~6000 kJ/day, males; ~7000
kJ/day), prescriptive eating plan in which participants received dietary advice and
instruction by a qualified dietician at baseline and every 2 weeks during clinic-based visits.
The eating plan included specific food quantities that were listed in a quantitative food
record completed daily by participants and used by the dieticians to provide feedback to
the participants during the clinic visits. This provided participants with clear dietary targets
and an opportunity for dietary self-management. Participants were also supplied with key
foods (~50% total energy) every 2 weeks of the RLP study to facilitate dietary compliance.
Approximately 60% of the enrolled participants also participated in a progressive
resistance exercise training program. This involved completing 3 moderate/high intensity
whole body resistance exercise training sessions per week (~45-minutes per session), at the
Commonwealth Scientific and Industrial Research Organisation (CSIRO) research
gymnasium under professional supervision. Pre- and post-RLP, clinical assessments
including body weight and composition, waist circumference and cardiometabolic risk
markers were assessed and have been previously reported elsewhere [11].
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Following the RLP, all participants were given advice on healthy food options and
planning strategies for maintaining the diet program without the professional support
provided during the study. Participants who did not participate in the resistance exercise
training program were also provided with general exercise advice and encouraged to
commence a regular exercise program to achieve physical activity recommendations for
T2DM [10]. Participants in the diet and exercise group were encouraged to continue the
same resistance exercise program with the additional incorporation of moderate aerobic
exercise.
Overall, 106 participants commenced and 84 completed the initial 16 week RLP. Of the
completers, 81 participants who provided permission for future contact were sent invitation
letters to participate in a follow-up visit at 1 year from study commencement. At this visit,
participants attended the CSIRO clinic during which body weight was measured using
calibrated electronic digital scales (Mercury, AMZ 14, Tokyo, Japan). Within one week of
the 1-year follow-up clinical assessment, a semi-structured qualitative phone interview was
conducted by an investigator external to the original research team that had conducted the
RLP. The interview opened with a brief summary of the original program to remind
participants of the circumstances of their participation, followed by a series of open-ended
questions. These were designed to identify reasons for the participation in the RLP,
difficulties and coping strategies associated with adherence to the RLP components during
the initial 16-week study and factors perceived to have impeded or assisted them in
maintaining components of the RLP following its completion.
Interview responses were transcribed and content analysed for common themes. The
number of times each theme was mentioned by individual participants was tallied and
expressed as a percentage of the total number of participants who completed the follow-up
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evaluation. Paired t-tests were used to evaluate combined group changes in body weight
over time and individual t-tests on the changes in body weight were used to test for
differences between the groups. All participants provided written informed consent. The
study was approved by the Human Research Ethics Committees of the CSIRO and the
University of Adelaide.
4.2.4. RESULTS and DISCUSSION:
4.2.4.1. Weight Loss
Of the 81 participants invited, 30 (37%) completed the 1-year follow-up. This consisted of
6 (19%) and 24 (49%) participants in the initial RLP diet only group and diet and exercise
groups, respectively. Overall, these participants maintained 8.8 ± 8.9 kg [mean ± standard
deviation] (63%) of the 13.9 ± 6.6 kg weight loss achieved during the RLP such that those
who participated weighed 8.1 ± 7.1% less than at Week 0 (P<0.001). Ten participants
(33%) maintained a weight loss greater than 10% of initial body weight and 17 participants
(57%) maintained a weight loss greater than 5%. Participants who completed the 1-year
follow up achieved greater weight loss during the 16-week RLP compared to the non
participants (-13.9±6.6kg [-12.8±4.6%] vs -8.4±4.5kg [-8.3±4.2%]); P<0.001) [11].
4.2.4.2. Reasons for participating in the RLP
Participants identified weight loss (63%) and improved diabetes control (40%) as the main
reasons for volunteering for the RLP. “I was fairly unhealthy, overweight, with health
problems. I wasn’t feeling very well, due to being overweight.” “I’d reached a point in my
life where I need a change in my health. This opportunity came along and I took it.”
Thirty-seven percent of participants also identified the desire to gain some diet and/or
exercise education as a reason for participating: “I needed some guidance and information
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on what I’m meant to be eating.” “I wanted to find out how I could go about controlling
sugar levels, and more about diet and exercise. Wanted to find out how to manage [T2DM]
myself.” It was clear that this was not the first attempt at weight or diabetes management
for a number of participants. “I could never lose weight before. People can tell you how to
lose weight, but sometimes you need that helping hand.” Overall, comments pointed to
both the achievement of improvements to health and the desire for increased education
about and mastery over their condition as motivating factors for participation in a RLP.
4.2.4.3. Ease of participation and reasons for persisting
On the subject of their participation in the RLP, the majority of participants (67%) reported
they found it relatively easy to comply with and complete the 16-week program. Those
parts of the program with which people reported experiencing difficulty were dietary
constraints (30%), sticking to alcohol limitations (23%) and dealing with cravings (17%).
Among participants assigned to the exercise program, the requirement to undertake
moderate to high intensity exercise (8%) and overcoming the initial challenge of doing
exercise (8%), were identified as being hard. The main factors identified by participants
that helped them to deal with difficult aspects of the RLP were the support, encouragement
and troubleshooting efforts of the staff (40%), personal persistence (50%), and to a lesser
extent, the motivating effects of having lost weight (13%) and/or achieved improvements
in diabetes control (13%). Similarly, a major reason given for completing the study was the
support from staff (37%). Other prominent explanations for successful completion were the
desire not to let down others or the sponsoring research organisation (30%) and, less
specifically, because they had made the commitment (27%). Prominent among
participants’ reports of their feelings at the completion of the program were feeling
healthier (30%), pride in their achievements (20%) and generally feeling good (30%). “I
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had a lot more energy, felt better in myself.” “Participating in this study gave me back
more confidence.”
The generally positive responses and the perceived relative ease of completion indicate a
high level of acceptability of the RLP in the targeted patient group. However, some of the
reasons provided for completing the program suggest that potential impediments for the
sustainability of healthy lifestyle behaviours may exist once the RLP has concluded.
Participants identified health benefits (weight loss and diabetes control) as key motivators
for commencing the study. However, non-health related reasons (not breaking a
commitment or not to let down external parties) were also provided for completing the
RLP. These responses suggest that health-related outcomes and knowledge alone may be
insufficient for maintaining some individuals’ motivation to sustain behaviours for
improving diabetes management. This is consistent with previous research that has
demonstrated that although knowledge enables patients to make informed decisions,
motivation to act is a result of a combination of many factors [12, 13]. In this case, the
external parties included the researchers, whose involvement can only ever be transitory. If
nothing else, this observation reminds us of a key limitation in the conduct of a short-term
clinical program for research purposes as a model for the delivery of an enduring lifestyle
intervention.
4.2.4.4. Difficulty in maintaining the dietary plan and routine post-RLP
When participants were asked at the 1-year follow-up what aspects of the diet plan they
had continued, 17% nominated breakfast only, 3% said lunch only, and 33% indicated
they continued to consume the same breakfast and lunch. Approximately one quarter of
participants (23%) indicated that they had continued to follow the entire diet plan, though
how scrupulously is not known. The suggestion in these figures that adherence presented
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fewer difficulties in the earlier than in the later parts of the day was supported by
participants’ own comments. Several participants reported that they had increased the size
of the evening meal. “I felt hungrier at night, so I needed a bit more meat”. “The problem
is the main meal – portion control….Plate is now full rather than half-full like before“.
Between-meal snacks were also identified as an impediment to adherence. One participant
said “I still have the same breakfast and lunches. Fall down at tea time, fall down with
snacks – chocolate and crisps. That’s my really bad thing”. Berteus Forslund et al. [14]
previously showed that although obese and non-obese women consume similar meals
during traditional meal times, obese women consume more meals or snacks in the
afternoon and evening/night time periods. Although the exact reason for the weight regain
observed during the post-RLP follow up period cannot be determined from the data
available, there are reasonable grounds to suspect that increased energy consumption
during the latter periods of the day may have been a large contributing factor. If so, weight
loss maintenance following a RLP may benefit from strategies focusing on reducing the
impact of overeating from snacks and overconsumption in meals, with particular emphasis
during the latter half of the day. This could potentially be achieved at least in part by
reducing the quantity or the energy density of foods [15], substitution of foods that induce
satiety (e.g. high protein foods) [16], and/or altering the daily distribution of food, although
further research is required to confirm this.
Another reason participants gave for discontinuing the diet program included the need for
‘variety’ (33%). “I just wanted variety. I didn’t want to stick with the exact diet”. Whether
this reflects desire for increased recipe choices using the allocated foods within the dietary
plan or alterative foods cannot be determined from the information collected. Irrespective
of the specific interpretation of the term ‘variety’, preference for food variety has
previously been shown in ad libitum studies to be a predictor of obesity [17] that may
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increase energy intake either through greater consumption of energy dense foods or
increased absolute food quantity. When food variety is offered either in consecutive
courses or within a single meal, hyperphagia and subsequent increased consumption
occurs, independent of the energy density and macronutrient composition of the food [14].
Alternatively, ‘liking foods absent in the meal plan’ has been previously identified as an
adherence barrier to a prescribed calorie-controlled diet [18]. Therefore, although variety
may be an impediment to healthy weight status in ad libitum conditions, it does not follow
that a lack of choice will enhance compliance with a weight-control diet. It maybe possible
that within a calorie-controlled prescriptive diet, providing increased variety through more
recipe ideas and food types (whilst maintaining the desired nutrient composition) may
improve dietary satisfaction and increase compliance. In the current study, it is important
to consider the diet plan used in RLP may have been more constrained, than might usually
be prescribed to achieve sustained dietary adherence, out of necessity to achieve the initial
study objectives [11]. Further research is required to investigate the effect of providing
greater consideration of individual tastes and food preferences (increased variety) on long-
term compliance with a calorie-controlled diet.
Finally, several participants also mentioned factors relating to breaking routine as being an
impediment to continuing the dietary plan. These included no longer being monitored.
“When discipline is gone, and you don’t have to do it, it’s easy to get back into bad
habits.” “I let things get in my way.” This was consistent with a previous study in non-
diabetics that reported loss of trial structure and difficulty in determining portion size as
the most frequently reported barriers for maintaining long-term weight loss following a
short-term diet and exercise weight loss intervention trial [19]. Also mentioned were
disrupting personal events, the pressures of social outings, and travel, all circumstances in
which people might find their dietary choices diminished by the change of environment or
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social pressures. “Going away [on extended travel] from my home environment broke the
routine. The loss of structure and being away from the comfort zone of my home
environment had a negative impact.” To counteract these disruptions, individualised
problem solving strategies may play an important role [20, 21].
4.2.4.5. Strategies used for continuation of the dietary plan post-RLP
When participants were asked how they managed to continue with the diet plan following
cessation of RLP, the key factors identified were maintaining portion control (27%): “I cut
down on portions. The big thing was realising how much I was eating before.”; continuing
the prescribed diet (20%); reducing ‘bad’ or fatty foods (20%): “Anything I’m not
supposed to eat, I don’t buy it, so it’s not in the house. If it’s not here, I can’t eat it.”;
learning to change dietary habits during the program (17%), and/or being motivated to
continue by their improvements in health, weight or diabetes control (23%): “My palate
has significantly changed. The long period of time [16 weeks] helped to change my
dietary habits. As a result, I continue to feel a sense of flow-on and benefits”. Apparent
from these comments was that a number of people had successfully developed new eating
habits to replace earlier, less healthy habits.
4.2.4.6. The importance of supervision and monitoring for dietary
compliance during the RLP
From many participants’ perspectives, factors contributing to program success included
continued supervision or having to report to someone (30%), having regular recorded
weight checks and diet visits (30%) and not breaking routine in general (10%). The loss of
the structural supports at the program cessation was therefore important. “You go from
intensive supervision to no supervision at all at the conclusion of the program. You don’t
have regular weigh-ins or anything like that afterwards. The weigh-ins and that sort of
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thing are incentives during the study. Left to your own devices, you don’t have that to
look forward to, tend to let things slide.” Generally speaking, under the close professional
supervision provided by the RLP, participants achieved good compliance with the
prescribed eating plan. It is likely that some participants were highly dependent on that
support and supervision and had not developed the skills and routines necessary to
continue to succeed independently. The ability to self monitor weight and food intake has
been identified as an important characteristic of successful weight loss maintainers [22]
that may represent an important educational consideration for achieving successful
transition of the RLP components to facilitate self-sustainability.
Over the longer-term, intensive lifestyle intervention has shown greater cost effectiveness
compared to pharmacotherapy for preventing type 2 diabetes [23]. Nevertheless, the
substantial cost of providing personal support is well documented [23] and this approach
may still not be a feasible model for sustainable lifestyle intervention, particularly when
costs are borne at a personal level. Further research is still required to investigate
alternative cost effective community health services and delivery mechanisms (e.g. internet
and phone) to achieve successful outcomes.
4.2.4.7. Continuation of exercise participation post-RLP
Of the 24 participants whose RLP involvement included, by random assignment, a
supervised, resistance exercise training intervention, 50% reported they were still attending
gym sessions at alternative locations. Thirty-three percent of participants did not continue
with any aspects of the prescribed exercise program, although several participants (13%)
indicated they had commenced other physical activities such as hiking and walking. A key
reason given by participants for continuing with exercise was the motivation derived from
the general improvements they experienced during the program (25%): “I had this great
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sense of achievement with what I’d done with the exercise. I was keen to keep it going”.
One participant stated “Making the commitment to start with, and finding the right facility
and access to the right program, that’s the hard part”. It appears that, for some people at
least, getting involved in a structured exercise program may lead to improvements that may
intrinsically motivate and facilitate exercise participation in the longer term.
Over recent years, strong evidence for the therapeutic benefits of resistance exercise
training for T2DM management has accumulated, and this form of exercise has been
advocated by leading health authorities [24]. Despite this, previous studies in patients with
T2DM have identified the fear of injury, low self-efficacy in respect of a novel or
unfamiliar exercise mode and the assumption that exercise will lead to increased muscle
mass and therefore body weight, as common barriers to participation in resistance exercise
training [25]. None of these factors were evident in the accounts provided by our
participants. It is therefore possible that commonly perceived barriers to resistance exercise
training may be overcome early by initial participation in a carefully supervised resistance
exercise training program, as in this case.
On a separate note, several participants identified exercise participation as a facilitator in
its own right of following a healthy dietary routine. “Without exercise I probably would
have got bored with the program.” Participation in regular physical activity was identified
as a key characteristic of individuals in the ‘National Weight Control Registry’ [22] and
the strongest correlate of weight loss after 1-year of the ‘Look AHEAD’ study [26]. It is
likely that, for some people at least, increased physical activity is important for its
motivational value as well as its physiological effects for weight and diabetes management.
A possible reason is that the immediate feedback available from exercise regimens –
beating a ‘personal best’ for example – is potentially highly rewarding and likely to
encourage more of the activity that led to the feedback. By comparison, the beneficial
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effects of improvements to diet can take some time to become apparent, thus causing
people to become disheartened.
4.2.4.8. Impediments to exercise participation post-RLP
Participants who did not continue or (in the case of diet-only participants) subsequently did
not commence a resistance training based exercise program identified reduced access to
gyms, equipment or similar exercise programs (29%) and the expense of public gyms
(21%) as major impediments. Participants also suggested that more appropriate or
accessible gyms or programs (38%), more affordable gym membership (21%) and having a
personal trainer or motivator (17%) would have made the exercise easier to continue over
the longer term. “It was difficult to find a similar program to the one [used in the study],
with some sort of monitoring. They [commercial gyms] tend to leave you to your own
devices, or push a program of their own.” “Access to a convenient gym would have made a
big difference. Also have to consider expense of a gym.” It needs to be borne in mind that
the majority of interview participants had completed 16 weeks of resistance exercise
training in the RLP and thus presumably overcome initial obstacles to participation.
Explanations for lack of continuation of exercise training emphasised problems of access
and affordability whereas participants’ explanations for lack of continuation of the diet
plan invoked factors relating to external support and motivation.
A recent study in T2DM patients [9] identified motivation and to a lesser extent the need
for better transition to ‘post-program realities’ of less support and supervision as the most
important factors for continuation of exercise participation 18 months following
completion of a 24-week RLP; however, factors relating to cost and facilities were not
evident. This discrepancy with our results could possibly be explained by the utilisation of
an aerobic rather than a resistance based exercise program in the latter study that may not
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have the same potential financial or equipment accessibility impediments. Additionally,
Casey et al. [9] used a weaning exercise program that gradually reduced the number of
weekly supervised sessions during the program from 3 to 1 and provided a high level of
transition towards independent unsupervised exercise. In contrast, our study participants
attended 3 supervised sessions per week for the entire 16-week duration of the RLP that
ceased at the completion of the study. Whether transition from the supervised research-
based program to independent exercise may have ameliorated perceived problems of
facility access as an exercise impediment is not known. One participant commented
“Better to taper off. Start off intensively and then taper off, rather than a sudden
conclusion”. Within the general community where this research study was conducted, a
number of appropriate exercise facilities and programs are available. This suggests the lack
of a transitional component (that includes both the identification and physical re-location to
community-based facilities) may have been responsible at least in part for the lack of
exercise continuation, rather than the lack of these services per se. On the other hand, Daly
et al. [27] conducted a 12-month study that included an initial 6-month gym-based
resistance exercise training program and incorporated a one month transition period into a
6-month home-based resistance exercise training program. However, during the home
based exercise, compliance reduced and fat mass rebounded to baseline levels suggesting
that even with weaning towards a prescribed home based program (with regular phone
contact), without personal support structured exercise training may be difficult to achieve.
Clearly, to maximise long term exercise participation, matters of cost, facilities, motivation
and possibly progressive transition strategies need to be considered for the successful
replacement of supervised clinical resistance exercise training programs with independent
exercise participation that achieves the recommended guidelines [10].
4.2.4.9. Research Limitation
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This is the first known study to assess self-reported impediments to and facilitators of
completion and subsequent adherence to a RLP incorporating an energy restricted diet and
resistance exercise training in overweight and obese patient with T2DM. However, a
limitation of this study is that the individuals who attended the follow-up achieved better
outcomes during the RLP, on average, than those who did not. It is therefore possible this
subgroup may also have had more success in maintaining their improvements and that the
factors identified by those participants may not be generalisable to participants who were
less successful or failed to complete the RLP. Nevertheless, this information provides
insight into factors perceived by patients with T2DM themselves as facilitating or
impeding their ability to maintain lifestyle behaviours following a RLP. Information of this
kind is potentially valuable in the development of strategies and programs for this target
population.
4.2.5. CONCLUSION
From the participants’ perspective, success of the RLP was perceived to be due largely to
high levels of professional support and supervision, and its absence post-program may
have reduced their ability to sustain these lifestyle behaviours without an alternative
provision of motivation and resources. The interview data provide some insight into what
people may experience in the outside world after they depart the research setting with its
structure and close monitoring and professional supports. Moreover, they remind us that
intensive programs put together for research purposes with the emphasis on compliance
may not be a realistic model for community intervention. This is especially evident when it
is acknowledged that the success of a research based weight management program may be
partially due to participants’ commitment to the research or the researchers. Development
of programs for long-term independent behaviour change requires identification of cost-
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effective and sustainable means of providing appropriate support and motivation and the
availability of affordable and accessible resources.
4.2.6. ACKNOWLEDGEMENTS:
We thank the volunteers who made the study possible through their participation. We
gratefully acknowledge Anne McGuffin for coordinating this trial; Elizabeth Hart for
conducting and scribing the interviews, Rosemary McArthur and Lindy Lawson for
nursing expertise.
4.2.7. AUTHOR CONTRIBUTIONS:
The authors’ responsibilities were as follows – Wycherley was responsible for the
conception and design of the study, coordinated the study, performed data analyses,
interpreted the data and wrote the manuscript. Mohr was responsible for the conception
and design of the study, data interpretation and contributed to the writing of the
manuscript. Noakes and Clifton contributed to the design of the study and the writing of
the manuscript. Brinkworth was responsible for the conception and design of the study,
coordinated the study, and contributed to data interpretation and the writing of the
manuscript. All authors agreed on the final version of the manuscript. None of the authors
had a conflict of interest in relation to this manuscript.
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CHAPTER 5: CONCLUSIONS
As obesity continues to escalate and the mean age of the population increases, it is
projected the incidence of T2DM will continue to rise to epidemic proportions. Effective
lifestyle intervention strategies that can promote weight loss and improve the maintenance
of weight status will aid in stemming the rise in obesity and T2DM prevalence and the
subsequent co-morbidities and financial costs to individuals and society. Lifestyle
modification that incorporates an energy reduced diet and exercise is effective for
improving weight status, glycemic control and CVD risk factors in patients with T2DM
and represents the cornerstone of T2DM management (43,44). The work conducted in this
thesis aimed to identify strategies that potentiate and sustain the benefits of lifestyle
modification that combines a caloric restricted diet and exercise training for
overweight/obese patients with T2DM.
Previous research suggests that manipulating the dietary macronutrient composition, and/or
participation in exercise training may alter the degree of weight loss and health status in
patients undertaking a hypocaloric, weight-reducing diet. A number of lifestyle
intervention studies have shown that increasing the dietary macronutrient content of
protein in a low fat, hypocaloric diet (by substitution of some carbohydrate with protein)
can provide beneficial effects for body composition (by mitigating FFM loss and
enhancing the reduction of FM) and cardiometabolic outcomes (82-88,93). Several studies
have also demonstrated benefits for these outcomes from participating in exercise training
during weight loss (55,115-119). However, to date there has been a paucity of well
controlled studies that have investigated the effects of manipulation of the macronutrient
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profile of a hypocaloric diet that is consumed as part of a holistic lifestyle intervention
program that incorporates exercise training.
Chapter 2 of this thesis demonstrated a 16-week lifestyle intervention program that
incorporates a structured energy restricted diet resulted in substantial improvements in
CVD risk factors and glycemic control irrespective of dietary macronutrient composition
or the addition of resistance exercise training in overweight and obese patients with T2DM.
However, an energy restricted high protein diet plus resistance exercise training induced
clinically relevant greater reductions in body weight and FM compared with either an
isocaloric high protein diet alone or an isocaloric standard protein diet alone or combined
with resistance exercise training. Based on these data, it would suggest that a high protein
diet plus resistance exercise training program may be a preferred treatment strategy in
overweight/obese individuals with T2DM.
Apart from the superior benefits of a high protein diet combined with exercise training for
reducing body weight and FM, demonstrated in Chapter 2, a separate line of evidence
suggests that manipulating the timing of protein intake in relation to resistance exercise
training maybe an important consideration for optimising body composition and
cardiometabolic outcomes by stimulating greater muscle protein synthesis and hypertrophy
(145). Mitigating the reductions in FFM that commonly occur with weight loss may also
mitigate weight loss related reductions in REE and therefore reduce the risk of long term
weight regain. In addition since skeletal muscle represents the largest mass of insulin
sensitive tissue, in patients with T2DM and other insulin-resistance related metabolic
conditions its preservation may benefit glycemic control.
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In Chapter 3 of this thesis, it was investigated whether the ‘superior’ benefits of a high
protein energy restricted diet plus resistance exercise training lifestyle intervention
program (identified in Chapter 2) could be further enhanced by manipulating the timing of
protein ingestion relative to resistance exercise. The study compared an energy restricted
high protein diet plus resistance exercise training program with a 21g protein load ingested
either immediately prior to exercise or 2 hours post exercise. The results of this study
showed that both treatments had similar weight loss, reductions in total body FM, FFM and
REE and improvements in cardiometabolic risk factors. It is concluded that within an
energy reduced high protein diet plus resistance exercise training intervention program
altering the timing of ingestion of a 21g protein source relative to resistance exercise
training appears to provide no additional benefit over a period of 16 weeks for overweight
and obese patients with T2DM.
A limitation of the research studies conducted in Chapters 2 and 3 of this thesis is that
these experiments were designed to mainly evaluate the applied outcomes of diet and
exercise based interventions. These data provide a valuable assessment of physiological
changes achievable with particular intervention strategies and provide insight for the
application of lifestyle intervention programs into clinical practice. However, the inclusion
of biochemical or genetic outcomes (including plasma amino acid concentrations, gene
expression, protein activation and muscle protein synthesis) would have provided a more
complex insight to the mechanisms that underpin the observed effects and may also
provide a more sensitive outcome measure (e.g. evaluating the muscle protein synthesis
response compared to actual changes in FFM). Another limitation of these experiments is
that the utilised intervention programs were only of short duration (16-weeks) and
therefore it remains unknown whether the beneficial effect of a high protein diet plus
resistance exercise program and/or the effect of manipulating the timing of ingestion of
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protein relative to exercise training would be altered and/or sustained if the duration of the
intervention program was extended over the longer term.
An interesting observation from the results obtained from Chapters 2 and 3 was that
despite the lack of any effect of a high protein diet and resistance exercise training program
for enhancing reductions in body weight and FM, no additional preservation of FFM or
reduction on HBA1c was evident with either manipulation of dietary composition, the
addition of resistance exercise training or the manipulation of the timing of protein
ingestion relative to exercise. Gannon et al. (90) have previously demonstrated in patients
with T2DM that compared to standard protein (15%) eucaloric control diet, those
following an isoenergetic high protein (30%) diet had greater reductions in HbA1c (–0.8%
vs. -0.3% absolute). Dunstan et al. (137) have previously observed a greater reduction in
HBA1c following 6 months of mild caloric restriction plus resistance exercise training
compared to caloric restriction alone (-1.2% vs. 0.4%) with participants experiencing only
a small reduction in body weight (~ -2.8 kg). It is plausible that with substantial weight
loss (as observed in Chapters 2 and 3) the potent hypoglycaemic effects of energy
restriction (183) may have masked any separate effects of exercise or diet composition for
reducing HbA1c.
For FFM, in addition to the previously discussed considerations of the relative protein
quantity prescribed in the high protein diet in Chapters 2 & 3 and the protein amino acid
profile of the snack in the Chapter 3 study, it is possible that the participant’s gender, the
rate of weight loss and the exercise training volume may have affected the outcome. Leidy
et al. (82) and Farnsworth et al. (83) both observed a mitigation in the reduction of FFM in
participants consuming a high protein diet, compared to those consuming a standard
protein diet. However these findings were reported in female participants only; protein
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kinetics are different in males and females, such that women have been observed to
oxidize less protein at rest compared to men (184 ,18 5). Whether gender differences
in protein metabolism equate to measurable differences in body composition outcomes
requires further investigation (186). Bryner et al. (131) showed that the addition of a
resistance exercise training program to caloric restriction prevented a reduction in FFM, in
that study participants in the resistance exercise training group were also mostly female (9
females vs. 1 male) and the prescribed exercise program had a higher training volume than
the program used in Chapters 2 and 3 (2-4 sets per exercise vs. 2 sets per exercise).
Similarly, Kraemer et al. (119) and Geliebter et al. (132), who showed the addition of a
resistance exercise training program to caloric restriction prevented a reduction of FFM,
both used a higher volume resistance exercise program (3 sets per exercise). The results of
these studies suggest increasing the training volume to amounts greater than those used in
Chapters 2 & 3 (>2 sets per exercise) may provide an advantage for muscle hypertrophy
(187) and preserve FFM in patients with T2DM undergoing caloric restriction weight loss,
although to date this has not been investigated.
Dunstan et al. (137) showed that during 6 months of mild caloric restriction the addition of
resistance training to caloric restriction increased FFM in patients with T2DM. However as
previously mentioned the weight loss achieved was only mild (~ -2.8 kg) which may have
induced a smaller relative FFM reduction (188).
There is some evidence that the branch chain amino acid leucine may be an important
independent factor for optimising the muscle protein synthesis response both throughout
the day and following exercise, with 7-12 grams per day and 2.5g per meal providing the
optimal metabolic response (189). In the Chapter 2 and 3 studies the high protein diet
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contained ~9 g.day-1 of leucine (based on absolute protein intake (189)) which, assuming
this mechanism, would have been sufficient to maximise the daily muscle protein
synthesis response (achievable with 7-12 grams per day of leucine (189)). However,
whether the leucine content per meal (i.e. the daily dietary protein distribution) was
optimal (>2.5g of leucine per meal (189)) was not determined and is a limitation of the
study. Therefore it is possible that despite achieving the planned daily protein intake
targets (and sufficient daily leucine dose) without an appropriate daily protein/leucine
distribution the chronic muscle protein synthesis response induced by the diet may not
have been maximised.
In the Chapter 3 study the snack provided 21g of protein (Sufficient to provide a near
maximal muscle protein synthesis response based on a protein dose stimulus (104)), the
leucine content of the snack we estimated to be ~1.7g (based on (189)). Although the
quantity of leucine utilised in the protein snack was below the optimal (>2.5g per meal)
leucine dose identified by Layman et al. (189), a recent study by Glynn et al. (190) showed
that when consuming a 10g dose of essential amino acids the muscle protein synthesis
response was similar when the amino acid dose contained either 1.8g or 3.5g of leucine.
This suggests that ~1.8g of leucine in an amino acid mixture is sufficient to elicit a
maximal protein anabolic response. Hence despite the absence of a direct measure of
muscle protein synthesis the protein/leucine stimulus provided in the protein snack was
likely to have been sufficient to assess the effect of the manipulation of timing of protein
ingestion relative to resistance exercise training in Chapter 3. It is unlikely, given that FFM
reduced similarly between dietary treatment groups in Chapter 2, that the underlying high
protein dietary pattern used in Chapter 3, had maximally stimulated the dietary muscle
protein synthesis response and was therefore responsible for a lack of effect of
manipulation of timing of protein ingestion.
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The lack of any observed effects on FFM combined with its potential importance for
facilitating long term weight maintenance and glycemic control poses a significant
question for future research; ‘How can FFM be preserved during weight loss?’.
Future research areas arising from the experiments in this thesis include investigating
alternative strategies to preserve FFM during weight loss with lifestyle intervention
combinations that that incorporate a hypocaloric high protein diet and resistance exercise
training, to identify the program that offers the greatest benefit to overweight and obese
patients with T2DM. This research should incorporate mechanistic outcome measures (e.g.
gene expression, plasma amino acid concentration, protein activation and muscle protein
synthesis) to provide further insight and understanding into the mode of effects. In
particular, future research should focus on a number of strategies including the daily
distribution of dietary protein, the primary source of protein (dairy vs. soy vs. meat [i.e.
essential amino acid content]), the absolute and body weight relative protein intakes
prescribed in the diet, the degree of caloric restriction or the characteristics of the exercise
training program (muscle groups being exercised, the number of sets, the number of
repetitions etc.). Specifically for Chapter 3, it would be of interest to investigate whether
using a more rapidly digested protein source adjacent to exercise (e.g. whey protein
isolate) would provide any beneficial effect.
Long-term sustainability of the benefits achieved with research-based, intensive lifestyle
intervention programs is often poor with rebound frequently occurring after the intensive
support of the program has ceased (133,165,166). Within the context of diet and exercise a
limited number of studies have identified several reasons why people with T2DM do not
participate in healthy lifestyle behaviours. However, self-perceived factors that may
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facilitate or impede the continuation of acquired healthy lifestyle behaviours are largely
unknown. In Chapter 4 of this thesis, participants involved in the 16-week research-based
lifestyle intervention studies described in Chapters 2 & 3 were followed up 1-year after the
commencement of these studies to identify self perceived impediments and enablers to
maintaining the healthy lifestyle behaviours acquired through participation in the research-
based lifestyle intervention programs which incorporated a weight loss diet with or without
exercise training. The collection of this data was conducted to provide an understanding of
the challenges experienced by individuals with T2DM in maintaining a lifestyle
modification program once the intensive support of a research setting has ceased. The
results showed that difficulties with the continuation of healthy lifestyle behaviours were
primarily due to the loss of external accountability and high levels of professional support
and supervision. The data generated in Chapter 4 also reminds us that intensive programs
assembled for research purposes with the emphasis on compliance may not be a realistic
model for community intervention.
A limitation of the research conducted in Chapter 4 is that although the data provides some
insight into factors that facilitate or impede continuation of diet and exercise components
in a community setting, since the factors were an expressed opinion whether the
availability of the desired resources/support would actually translate into success still
remains unknown and requires further exploration.
Although substantial improvements in health markers are achievable with short term,
research based, diet and exercise lifestyle intervention there are clearly numerous barriers
to overcome if this success is to be sustained long term within a community setting, outside
of the research clinic environment. Subsequently future research is required to identify and
evaluate effective strategies and support measures that can be achieved within the
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constraints of available community resources to assist in the translation of clinical
outcomes to sustained community programs. This could be investigated with the use of
long term efficacy based studies using community based resources and delivery models.
The overall findings from the research conducted in this thesis provides information that
can be used by health professionals and policy makers for the development of evidence
based recommendations for the management of T2DM through diet and exercise based
lifestyle intervention.
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