Diet and Metabolic Syndrome: Practical Approaches to Lowering Risks of Heart Disease and Diabetes

Kevin C. Maki, PhD, FNLA, FTOS

Midwest Center for Metabolic & Cardiovascular Research and

DePaul UniversityChicago, Illinois

Diet and Metabolic Syndrome: Practical Approaches to Lowering

Risks of Heart Disease and Diabetes

The Metabolic Syndrome

· A cluster of risk factors for heart disease and type 2 diabetes that occur together more than would be predicted by chance

· Has been known by several names:– Syndrome X – Insulin Resistance Syndrome– The Deadly Quartet

Metabolic Syndrome: Prevalence in U.S. by Age – 2001 ATP III Defn.

0

10

20

30

40

50

20-29 30-39 40-49 50-59 60-69 70+

Age (years)

Prev

alen

ce (%

)

Men Women

Ford, et al. JAMA. 2002;287:356-9.

Metabolic Syndrome Definition (AHA/NHLBI Revised)

· Any three of the following:– Abdominal obesity: waist circumference

>102 cm (40 inches) for men > 88 cm (35 inches) for women

– Triglycerides: ≥150 mg/dL (or meds)

– HDL cholesterol (or meds) < 40 mg/dL (men) < 50 mg/L (women)

– Blood pressure: ≥130/85 mmHg (or meds)

– Fasting glucose: ≥100 mg/dL (or meds)

Additional Features of the Metabolic Syndrome (Under the Surface)

· Insulin resistance and hyperinsulinemia

· Small, dense LDL particles (Pattern B)

· Pro-thrombotic and inflammatory states– ↑ fibrinogen– ↑ plasminogen activator inhibitor-1– ↑ C-reactive protein

· Elevated uric acid

· Hypertrophy or hyperplasia– Heart, blood vessels, prostate, tumors

Diabetes Mellitus: a US Pandemic

• Diabetes mellitus affects 25.8 million people or 8.3% of the US population (1/3 undiagnosed)

• It is estimated that 79 million US adults have pre-diabetes

• Type 2 diabetes mellitus (T2DM) is a major cause of heart disease and stroke, and is the leading cause of kidney failure, lower-limb amputations, and blindness

• Annual economic impact (direct and indirect): $174 billion

http://www.ndep.nih.gov/diabetes-facts/#howmany

Pathogenesis of Type 2 Diabetes: the Traditional Triumvirate

DeFronzo RA. Diabetes. 2009;58:773-795.

HGP = hepatic glucose production

Glucose and Insulin Responses During 100 g Oral Glucose Tolerance Test (OGTT)

0 60 12080

90

100

110

120

130

Normal Insulin Resistance

Time (min)

Plas

ma

Glu

cose

(m

g/dL

)

0 60 1200

20406080

100120140160180

NormalInsulin Resistance

Time (min)Pl

asm

a In

sulin

(m

U/L

)

Maki KC. Unpublished data.

Beta-Cell Function in NFG, IFG, and Diabetes

NFG IFG Diabetes0

200

400

600

800

1000

1200

1400

Mat

suda

Inde

x * A

UC

ins/

glu

Maki KC, et al. Nutr J. 2009;8:22.

Oral disposition index

All comparisons p < 0.001

0 30 60 90 120 150 180 210 2400

20

40

60

80

100

120

140 NFGIFGDiabetes

Time (min)

Insu

lin (m

U/L

)

Glucose and Insulin Responses During a Liquid Meal Tolerance Test

Maki KC, et al. Nutr J. 2009;8:22.

0 30 60 90 120 150 180 210 2400

50

100

150

200

250 NFGIFGDiabetes

Time (min)

Glu

cose

(mg/

dL)

NFG = normal fasting glucose, IFG = impaired fasting glucose

Pathogenesis of Type 2 Diabetes: Quartet of Essential Defects

DeFronzo RA. Diabetes. 2009;58:773-795.

DPP-IV = dipeptidyl peptidase-4TZDs = thiazolidinediones

Role of Nocturnal Free Fatty Acids (FFAs) in Diet-Induced Obesity/Insulin Resistance in Dogs

Dashed linesindicate 9:00 amfeeding

Open bars arepre- and filledbars are post-diet-inducedobesity

Kim SP, et al. Am J Physiol Endocr Metab. 2007;292:E1590-E1598.

Raising FFA Induces Insulin Resistance in Healthy Subjects

FFA level (µmol/L)• Saline n = 422• Intralipid n = 588

Mathew M, et al. Cardiovascular Diabetology. 2010:9:9.

LBM = lean body mass

Cusi K, et al. Am J Physiol Endocrinol Metab. 2007;292:E1775-E1781.

Lowering FFA with Acipimox Increases Insulin Sensitivity

Relation Between Weight Loss and Insulin Sensitivity According to Dietary CHO

SSPG = steady-state plasma glucose

McLaughlin T, et al. Am J Clin Nutr. 2006;84:813-821.

Defects in Dysglycemia: Muscle, Liver, Pancreas, Adipose Tissue

• Insulin resistance Reduced ability of a given circulating level of insulin to enhance tissue

uptake of glucose (particularly in skeletal muscle) Reduced ability of a given circulating level of insulin to suppress hepatic

glucose output and release of FFA from adipose depots• Excessive hepatic glucose output

Hepatic insulin resistance Excess glucagon release + other factors (e.g., neural control)

• Pancreatic beta-cell dysfunction Reduced insulin response to a rise in plasma glucose

Reduced sensitivity to glucose signalingIncretin resistance and deficiencyLower insulin secretion capacity in advanced T2DM

Risk Factors for Diabetes

· Pre-diabetes (IGT, IFG, elevated HbA1C)· Overweight/obesity· Physical inactivity· Age ≥45 y· Family history of diabetes· Metabolic syndrome and its components· Certain racial and ethnic groups (e.g., Non-Hispanic Blacks,

Hispanic/Latino Americans, Asian Americans, Pacific Islanders, American Indians and Alaska natives)

· Women who have had gestational diabetes, or given birth to a baby weighing ≥9 lbs

http://www.diabetes.org/diabetes-basics/prevention/risk-factors/

Pre-Diabetes

Test Range of values

Fasting plasma glucose (FPG) 100-125 mg/dL

2-hr plasma glucose, 75 g OGTT 140-199 mg/dL

Glycated hemoglobin (HbA1C) 5.7-6.4%

ADA. Diabetes Care. 2010;33(Suppl 1):S62-S69.

Diabetes Prevention Studies Overview: Hypoglycemic Agents

Study Subjects Total N F/U (y) Intervention Diabetes Risk ↓

U.S. DPP IGT 3234 2.80.9

MetforminTroglitazone

31%75%

India DPP IGT 531 2.5 MetforminMetformin + diet/exercise

26%28%

India DPP-2 IGT 407 3.0 Pioglitazone NSU.S. ACT NOW IGT 602 2.4 Pioglitazone 72%U.S. TRIPOD Prior GDM 236 2.5 Troglitazone 55%Sweden XENDOS IGT or NGT 3305 4.0 Orlistat +

diet/exercise45%

Canada DREAM IGT 4894 3.0 Rosiglitazone 58%Canada CANOE IGT 207 3.9 Rosiglitazone +

metformin66%

EU/Can Stop-NIDDM IGT 1429 3.3 Acarbose 25%

ACT NOW = Actos Now for the prevention of diabetes; TRIPOD = TRoglitazone in the Prevention Of Diabetes; XENDOS = XENical in the prevention of diabetes in obese subjects; DREAM = Diabetes REduction Assessment with rampiril and rosiglitazone Medication; CANOE = CANadian Normoglycemia Outcomes Evaluation

Diabetes Prevention Studies Overview: Lifestyle Modification

Study Subjects Total N Follow-up (y)

Intervention Diabetes Risk ↓

US DPP IGT 3234 2.8 Diet + exercise 58%

China Da Qing

IGT 530 6.0 Diet Exercise

Diet + exercise

35%39%32%

Finland DPP IGT 522 3.2 Diet + exercise 52%

India DPP IGT 531 2.5 Diet + exercise 29%

Japan DPP IGT 458 4.0 Diet + exercise 67%

Spain PREDIMED

CHD risk factors (≥3)

418 4.0 Olive oil- or Nut-based

Mediterranean diet

43%39%

CHD = coronary heart disease DPP = Diabetes Prevention Program PREDIMED = Prevención con Dieta Mediterránea

Diabetes Prevention ProgramLifestyle Targets: 7% Weight Loss, 150 min/wk Activity

DPP N Engl J Med 2002; 346:393-403.

Effect of Lifestyle Changes (Diet and Exercise) on Incidence of T2DM

· A review of studies of 4864 high-risk individuals followed for 2.5-6 y reported

– Lifestyle changes may lower incidence of T2DM by 28-59%– 6.4 individuals need to be treated to prevent or delay 1 case of diabetes

through lifestyle changes (over 3-4 years)– Various weight loss diets (low fat, high protein, or Mediterranean) may be

effective (weight loss more important than how achieved)– Maintenance of weight loss requires regular exercise with additional

expenditure of ~2000 kcal/week (~15 miles of walking)

Walker KZ, et al. J Hum Nutr Diet. 2010;23:344-352.

Meta-Analysis: Estimates of Associations Between Macronutrient Intake and T2DM Risk

Macronutrient Relative Risk 95% Confidence Interval (CI)

Carbohydrate* 1.11 1.01, 1.22

Fat 0.93 0.86, 1.01

Vegetable Fat† 0.76 0.68, 0.85

Protein 1.02 0.91, 1.15

* A high vs. low intake of total CHO was associated with higher risk of T2DM (p = 0.035).† A high vs. low intake of vegetable fat was associated with lower risk of T2DM (p < 0.001).

CHO analysis: 10 cohort studies; fat analysis: 14 cohort studies; protein analysis: 4 cohort studies

Alhazmi A, et al. J Am Coll Nutr. 2012;31:243-258.

Risk of Developing T2DM Associated with Increased Glycemic Index and Load

Barclay AW, et al. Am J Clin Nutr. 2008;87:627-637.

Results for glycemic load were similar to those for glycemic index.Glycemic load is affected by carbohydrate intake and glycemic index.

Dietary Fibers and Diabetes Risk

Schulze et al. Arch Intern Med 2007;167:956-965.

Nurses Health Study: Relative Risk of T2DM by Different Levels of Cereal Fiber and Glycemic Load

Salmeron J, et al. JAMA. 1997;227:472-477.

Resistant Starch Intake Increases Insulin Sensitivity in Overweight and Obese Men

Maki KC, et al. J Nutr. 2012;142:717-723.

HAM-RS2 = high-amylose maize type 2 resistant starchSI = insulin sensitivity

Effect of Short-Term (24 hr) Resistant Starch Consumption on Breath H2 and FFA (NEFA)

Robertson MD, et al. Diabetologia. 2003;46:659-665.

Closed symbols are control and open symbols are resistant starch

Fermentable Dietary Fiber and Insulin Sensitivity

Sleeth et al. Nutrition Research Reviews 2010;23:135–145

Food Sources of Fermentable Fibers

· Oats and barley (beta-glucan)· Prunes, apples and pears (pectin)· Nuts and seeds· Legumes· Multi-grain breads (those with ≥3 g fiber per slice)

Sugar Sweetened Product Consumption Reduce Insulin Sensitivity

Parameter Baseline Dairy (Δ) SSP (Δ) Difference P-value*

Mean (SEM) or Median (Q1, Q3)MISI

4.16 (2.81, 5.98)

-0.10 (-0.96, 0.54)

-0.49

(-1.01, 0.14)0.39

0.290

HOMA2-%S117.8

(86.2, 147.1)

1.3 (-21.3, 29.3)

-21.3

(-33.1, -3.30)22.6

0.009

Abbreviations: AUC, area under the curve; HOMA2-%B, homeostasis model assessment 2-β-cell function; HOMA2-%S, homeostasis model assessment 2-insulin sensitivity Matsuda insulin sensitivity index; SSP, sugar-sweetened products.*P-values were calculated from a repeated measures ANCOVA model between dairy and SSP conditions (N = 34).

Dairy = 2 servings per day of 2% milk and 1 serving of yogurtSSP = 2 servings per day of sugar-sweetened cola and 1 serving of non-dairy pudding

Maki et al. Experimental Biology 2014

Differences in Lipids and 25-OH Vitamin D Between Dairy and Sugar-sweetened Product Conditions

Parameter* Baseline (mg/dL) Dairy (%Δ) SSP (%Δ) Difference P-value*

Mean (SEM) or Median (Q1, Q3)

LDL-C 125.7 (5.82) -0.0 (2.2) -0.1 (2.2) 0.1 0.947

Non-HDL-C 153.4 (6.95) -0.4 (2.0) 0.5 (2.2) -0.9 0.752

TC 196.7 (6.81) -0.6 (1.5) -0.7 (1.5) 0.1 0.953

HDL-C 44.3 (1.53) 0.8 (2.0) -4.2 (1.3) 5.0 0.015

Triglycerides 133.2 (7.33) -2.0 (4.7) 6.0 (4.6) -8.0 0.20925(OH)D (ng/mL) 24.5 (2.2) 11.7 (5.6) -3.3 (3.4) 15.0 0.022

Abbreviations: -C, cholesterol; HDL, high-density lipoprotein, LDL, low-density lipoprotein; SSP, sugar-sweetened products; TC, total cholesterol.*P-values were calculated from a repeated measures ANCOVA model between dairy and SSP conditions (N = 34).

Dietary Macronutrient Compositionand T2DM Risk

· Macronutrient changes and T2DM risk Reduce intakes of foods high in refined carbohydrates (CHO)

Sugars and refined starches

Potential options for substitution CHO-rich foods with low glycemic index, particularly whole grains that

contain cereal and fermentable fibers Fats (particularly vegetable fats) Proteins Alcohol

High Cereal Fiber or Moderate Cereal Fiber and Moderate Protein Diet Improves Insulin Sensitivity

Weickert MO, et al. Am J Clin Nutr. 2011;94:459-471.

Nutrient Control High cereal fiber (HCF)

High PRO (HP)

Mix

CHO, % energy 55 55 40-45 45-50

PRO, % energy 15 15 25-30 20-25

Fat, % energy 30 30 30 30

Dietary fiber, g ~20 ~50 ~20 ~35

Values are % of baseline, 3 = sig diff from HP, 4 = sig diff from baselineN = 111 overweight adults; M value = insulin-mediated glucose uptake as a measurement of whole-body insulin sensitivity; EGP = endogenous glucose production

Meta-Analysis of 74 Trials of High Protein vs. Lower Protein Diets on Health Outcomes

Santesso N, et al. Eur J Clin Nutr. 2012;66:780-788.

Potential Mechanisms for Higher Protein Diets and Weight Loss

Hu FB. Am J Clin Nutr. 2005;82 (suppl):242S-247S.

Energy Expenditure Higher After Protein vs. CHO Intake

Acheson et al., Am J Clin Nutr 2011;93:525-534

Appetite Visual Analog Scale Ratings Following Low vs. High Protein Breakfasts

N = 34 healthy women; randomized controlled crossover trial30 and 39 g protein produced greater appetite control throughout the morning vs. NB and LP (p < 0.001)

LP = low protein breakfast (3 g protein), NB = no breakfast (water only)

Rains TM, et al. Poster presented at The Obesity Society. November, 2013.

Energy Intakes at Lunch Following Low vs. High Protein Breakfasts

LP = low-protein breakfast (3 g protein), NB = no breakfast (water only)

Rains TM, et al. Poster presented at The Obesity Society. November, 2013.

N = 34 healthy women; randomized controlled crossover trial

Different letters indicate significant difference (p < 0.05); energy intake at lunch for 30 g Pro vs. LP was p = 0.053

Effect of a Reduced Glycemic Load Diet (Lower CHO, Higher Protein and Fat) on Weight Loss

♦ Control diet (low-fat, portion control – 46/19/37% CHO/PRO/Fat)■ Reduced glycemic load diet (32/26/42% CHO/PRO/Fat)

Maki KC, et al. Am J Clin Nutr. 2007;85:724-734.

POUNDS LOST: All Diets Resulted in Clinically Meaningful Weight Loss, But…

N = 811 overweight adults

Sacks FM, et al. N Engl J Med. 2009;360:859-873.

Macronutrient intake targets at 6 and 12 months were not met

POUNDS LOST: Targeted Differential PRO Intake Was Not Achieved

Intake/d Low Fat/Average PRO

Low Fat/High PRO

High Fat/Average PRO

High Fat/High PRO

6 mo 2 y 6 mo 2 y 6 mo 2 y 6 mo 2 y

CHO, % 57.553.2 53.4

51.3 49.1 48.6 43.0 42.9

PRO, % 17.619.6 21.8

20.8 18.4 19.622.6 21.2

Fat, % 26.226.5 25.9

28.4 33.9 33.334.3 35.1

Sacks FM, et al. N Engl J Med. 2009;360:859-873.

Targets

Protein and Glycemic Index in Weight Loss Maintenance

· 548 participants completed the study

· Results suggest that the high-protein, low glycemic index diet may help to reduce weight regain, although the effect was modest (3-4 lb)

LP = low protein (13% en)HP = high protein (25% en)LGI = low glycemic indexHGI = high glycemic index

Larsen TM, et al. N Engl J Med. 2010;363:2102-2113.

Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart)

Targets (% kcal) CARB PROT UNSATCHO 58 48 48

PRO 15 25 15

Fat 27 27 37

MUFA 13 13 21

PUFA 8 8 10

SFA 6 6 6

CARB: carbohydrate-rich diet similar to Dietary Approaches to Stop HypertensionPROT: replacement of 10% of CHO calories with PRO (mixed source)UNSAT: replacement of 10% of CHO calories with unsaturated fats

MUFA = monounsaturated fatty acidsPUFA = polyunsaturated fatty acidsSFA = saturated fatty acids

N = 164 individuals with prehypertension or stage 1 hypertension without diabetesEach feeding period lasted 6 wks, and body weight was kept stable

Appel LJ, et al. JAMA. 2005;294:2455-2464.

OmniHeart: Results for Measures of Insulin Sensitivity

Baseline (BL)

UNSAT vs CARB

PROT vs CARB

UNSAT vs PROT

Mean Mean (95% CI) between-diet from BL

QUICKI 0.35 0.005*(0.000, 0.009)

0.001(-0.004, 0.007)

0.003(-0.002, 0.009)

1/HOMA-IR 0.74 0.11*(0.03, 0.20)

0.04(-0.07, 0.14)

0.08(-0.05, 0.20)

*p < 0.05 (for 1/HOMA-IR the increase compared to CARB was ~15%)QUICKI = quantitative insulin sensitivity check1/HOMA = homeostasis model assessment of insulin resistance reported as the reciprocal

Gadgil MD, et al. Diabetes Care. 2013;36:1132-1137.

Other Dietary Factors Associated with Lower Risk of T2DM – Need More Research Before Specific

Recommendations· Coffee

– Especially in place of sugar-sweetened beverages· Polyphenols

– Found in some foods and beverages– Berries, cherries, cranberries, coffee, tea, cocoa

· Cinnamon – High doses of cinnamaldehyde

· Magnesium– High levels in whole grain foods

· Chromium· Dairy foods (esp. fermented dairy products)· Moderate alcohol consumption

Dietary Supplements and Diabetes

· Despite an increasing body of literature investigating the use of natural [dietary] supplements on the treatment of diabetes, the American Diabetes Association (ADA) does not recommend their use because:

– Clinical evidence showing efficacy is insufficient– Standardized formulations are [often] lacking

Allen RW. Ann Fam Med. 2013;11(5):452-459

Theoretical Causal Model for Effects of Coffee on Risk of T2DM

• COFFEE• Chlorogenic

acids• Trigonelline• Quinides

• Micronutrients

• GUT• GIP

• GLP-1• Glusose

absorption• Iron absorption

• β-cell function

• Insulin resistance

• Glycemic control • T2D

• LIVER• G-6-Pase• Gluconeog

enesis• Inflammatio

n

• Oxidative

stress

Coffee Intake and Reduced Risk of T2DM: Potential Mechanisms?

· Anti-inflammatory (Frost Anderson, Jacobs, et al. AJCN 2006)– Coffee is a rich source of minerals and phytochemical compounds,

including phenolics, that may confer protection from systemic inflammation

Systemic inflammation has been found to predict type 2 diabetes independent or traditional risk factors

· Antioxidants (Svilaas et al., J Nutr 2004)– Coffee is a rich source of antioxidant compounds, may confer

protection from oxidative stress Oxidative stress is elevated in obesity and type 2 diabetes

Polyphenols

· Natural phytochemical compounds in plant-based foods (such as fruits, vegetables, whole grains, cereal, legumes, tea, coffee, wine and cocoa)

· More than 8000 polyphenolic compounds have been identified

· Several biological activities and benefits have been documented:– Examples include:

Antioxidant Anti-allergic Anti-inflammatory Anti-viral / anti-microbial

· May modulate important cell signaling ways:– Examples include:

Nuclear factor kappa-β (NF-κβ) Activator protein-1 DNA binding (AP-1) Extracellular signal-related protein kinase (ERK)

Bahadoran Z. J Diab Met Disor. 2013;12:43-52

Polyphenols: 2 Major Categories· Phenolic Acids (1/3 of polyphenolic compounds in diet)

– Hydroxybenzoic acid derviatives Protocatechuic acid Gallic acid p-hydroxybenzoic acid

– Hydroxycinnamic acid derivatives Caffeic acid Chlorogenic acid Coumaric acid Ferulic acid Sinapic acid

· Flavonoids (the most abundant polyphenols; more than 4000 types identified)

– Anthocyanins– Flavonols– Flavanols– Flavanones– Flavones– Isoflavones

Examples of Food Sources of Polyphenols

· Phenolic acids – Berry fruits– Kiwi– Cherry– Apple – Pear – Chicory– Coffee

· Flavonoids– Anthocyanins: berries

family, red wine, red cabbage, cherry, black grape, strawberry

– Flavonols: onion, curly kale, leeks, broccoli, blueberries

– Isoflavones: soybeans and soy products

Cinnamon

· Hypothesized to provide health benefits, such as lowering serum lipids and blood glucose

· Proposed active component: cinnamaldehyde– Insulinotropic effects have been investigated, thought to be responsible for:

Promoting insulin release Enhancing insulin sensitivity Increasing insulin disposal Exerting activity in the regulation of protein-tyrosine phosphatase 1β (PTP1β ) and insulin

receptor kinase

· Results of 2013 systematic review and meta-analysis evaluating the effects of cinnamon on glycemia and lipid levels:

– Statistically significant reductions in fasting plasma glucose, total cholesterol, LDL-cholesterol, and triglycerides; statistically significant increase in HDL-cholesterol

– No effect on hemoglobin A1c

Allen RW. Ann Fam Med. 2013;11(5):452-459

Magnesium

· Prospective studies those with higher Mg intake are 10-47% less likely to develop T2DM– Only 50% of Americans (1 yr+) achieve recommended dietary allowance for Mg (400-420 mg/day for

adult men & 300-310 mg/day for adult women)

· Results from several clinical trials (short duration, ≤ 6 months) of Mg in those with and without diabetes found that supplementation may improve:

– Glycemic control, insulin sensitivity, beta-cell function Randomized, placebo-controlled trial in obese, nondiabetic, insulin-resistant subjects 6 months of 365 mg/day

Mg significantly lowered fasting glucose, fasting insulin, insulin resistance and improved insulin sensitivity Three-month supplementation of Mg in subjects with other risk factors (such as mild hypertension or

hypomagnesemia) found to improve insulin sensitivity and pancreatic β-cell function Low-Mg diets given to healthy subjects has been shown to impair insulin sensitivity after 3 weeks

· Experimental evidence from animal studies supports association between Mg and insulin sensitivity:

– Animals fed Mg-deficient diets insulin sensitivity of peripheral tissues is reduced via decrease autophosphorylation of tyrosine kinase (a component of the β-subunit of the insulin receptor, which Mg is a cofactor)

Hruby A. Diab Care. 2014;37:419-427

Chromium

· Chromium deficiency may aggravate carbohydrate intolerance· Late 1990’s, two randomized, placebo-controlled studies in China found

that chromium supplementation had beneficial effects on glycemia

· Results from small studies indicate that chromium may have a role in:– Glucose intolerance– Gestational diabetes – Corticosteroid-induced diabetes

· American Diabetes Association stated that benefit from chromium has not been clearly demonstrated, therefore, chromium supplementation in individuals with diabetes or obesity can not be recommended

Cefalu WT. Diab Care. 2004;27(11):2741-2751

Dairy Foods

· 2010 Dietary Guidelines for Americans: “Moderate evidence…indicates that intake of milk and milk products is associated with a reduced risk of cardiovascular disease and type 2 diabetes and with lower blood pressure in adults.”

· Potential mechanisms of action– Dairy foods are important sources of nutrients:

Calcium – increases insulin secretion; is essential for insulin-responsive tissues (i.e., skeletal muscle and adipose tissue) and may reduce insulin resistance

Vitamin D – associated with decreased risk of diabetes, possibly by influencing insulin secretion and decreasing insulin resistance

Whey protein – reduce body weight gain in animal models Magnesium – associated with reduced diabetes risk (in epidemiologic studies) and with

improved insulin sensitivity in some experimental studies but data are limited Fat – trans-palmitoleic acid, a biomarker of dairy fat, was inversely associated with risk of

type 2 diabetes, suggests possible protective effect of specific milk-fat components

Aune D. Am J Clin Nutr. 2013;98(4):1066-1083

Moderate Alcohol Consumption

· Results of meta-analysis: ~30% reduced risk of type 2 diabetes with moderate alcohol consumption

· Proposed mechanisms of action with moderate use:– Increased HDL cholesterol– Anti-inflammatory effect – Enhanced insulin sensitivity with lower plasma insulin

concentrations

Koppes LLJ. Diab Care. 2005;28(3):719-725

Characteristics of a Low-RiskDietary Pattern

Maki KC, et al. AJC. 2004;93(11A):12C-17C.

Conclusions

· Metabolic syndrome is a cluster of risk factors for both T2DM and cardiovascular disease that cluster together and are related to insulin resistance.

· T2DM results from a combination of metabolic defects including insulin resistance in skeletal muscle and liver, pancreatic beta-cell dysfunction, and excessive adipose tissue lipolysis.

· Results from intervention trials with weight loss + exercise and a Mediterranean diet intervention, as well as pharmaceutical interventions, show that T2DM can be prevented or delayed in those with pre-diabetes.

· A diet high in carbohydrate, particularly refined (high GI) carbohydrate, is associated with increased risk for T2DM.

Conclusions

· Substituting foods high in refined carbohydrate with alternatives tends to improve the T2DM/metabolic syndrome risk factor profile

· Substitutions which show the greatest promise and which warrant further research include:

– Carbohydrate-rich foods Low glycemic index High in cereal and fermentable fibers (improved insulin sensitivity)

– Protein-rich foods Mainly related to appetite and weight effects

– Vegetable (unsaturated) fats– Foods high in polyphenols, fermented dairy products, moderate

alcohol in those who drink No more than 14 drinks per week for men and 7 per week for women