Diabesity

DiabesityDiabesity

Jay Shubrook DO FACOFPAssociate Professor of Family Medicine

Director, Diabetes FellowshipOhio University Heritage College of

Osteopathic Medicine

Obesity and DiabetesObesity and Diabetes• Review the married epidemics of obesity and

diabetes• Review how diabetes can be prevented in obese

individuals• Review how you can improve obesity and

diabetes simultaneously• Discuss different treatments for different types of

diabetes

Human EvolutionHuman Evolution

US Obesity EpidemicUS Obesity Epidemic• 17% of all US deaths from obesity

o approx. 300,000 deaths/yearo Obesity equals smoking as cause of preventable deatho Shortens life span 5 -22 years

• Extremely obese white male 20-30 o Lose 13 yrs of lifeo Mortality 12x higher if BMI >40

Years of Life Lost Due to Obesity, JAMA January 8, 2003:89;2;187-193Obesity Among US Immigrants Subgroups by Duration of Residence JAMA Dec 15, 2004.

ObesityObesity• Greatest US health expenditure• Social and ethnic differences in obesity

o Greater in women x 2o Greater among Black Americans

• Women>> meno Greater among non-HS gradso Largest increase in ages 19-28

• 75% of those with extreme obesity have a co-morbid disease

1999

Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1999, 2009

(*BMI 30, or about 30 lbs. overweight for 5’4” person)

2009

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Risk of Type 2 Diabetes as a Risk of Type 2 Diabetes as a

function of BMIfunction of BMI

0102030405060708090

100

<22 22-22.9

23-23.9

24-24.9

25-26.9

27-28.9

29-30.9

31-32.9

33-34.9

>35

Adjusted relativerisk of diabetes

Colditz GA et al. Ann Int Med, 1995BMI Range

2008

Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes

Obesity (BMI ≥30 kg/m2)

Diabetes

1994

1994

2000

2000

<14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0%

<4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0%

CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics

2008

What about closer to What about closer to home?home?

Childhood Obesity in Childhood Obesity in OhioOhio

• 1/3 of 3rd graders were overweight or obese• Higher rates in

o Hispanic and Non-Hispanic Black childreno Children in Appalachian countieso Low income childreno Children who watched at least 3 hours TV/dayo Highest in kids who drank >1 sweetened

beverage per day

ODH 2009-2010 data

Childhood Obesity in Childhood Obesity in OhioOhio

ODH 2009-2010

Non Hispanic white

Non-Hispanic Black

Hispanic AppalachianCounties

overweight 15.2% 20.5% 23.0% 17.1%

obese 17.2% 19.8% 30.7% 22.8%

ODH 2009-2010 data

Childhood Obesity in Childhood Obesity in OhioOhio

Rural Urban Suburban

Free and reduced meals

Non enrolled in free school plan

overweight

16.5% 16.1% 16.4% 16.9% 15.9%

obese 19.1% 18.4% 14.3% 23.4% 13.8%

ODH 2009-2010 data

Risk Factors for Risk Factors for ObesityObesity

• Obese parentso Before age 3 parental weight predicts obesity more than

child’s weighto If 1 parent is obese child’s risk x3o If both obese odds ratio 10

• 10% chance normal weight

Whitaker NEJM 1997

Risk Factors for Risk Factors for ObesityObesity

• Environmental Factorso Portion size (market portions are 2-8 times larger than

recommended USDA and FDA recs)o Sweetened beverages

• Increasing since 1970o Socioeconomic status inversely related to obesityo Energy density and food cost inversely relatedo Increase in sedentary leisure time

• 26% watch more than 4 hours of TV time per day• 67% watch more than 2 hours

Obesity Related Co-Obesity Related Co-morbiditiesmorbidities

• Glucose tolerance tests in obese childreno ABnormal results in

• 29% non-Hispanic white children • 41% of African American children• 50% of Hispanic children• 53% of Asian/Pacific Island children• 66% of American Indian children

Weiss R Diabetes Care 2005

Childhood Obesity Childhood Obesity ComplicationsComplications

• Overall Diabetes Risk (children born in 2000)o 1 in 3 boyso 2 in 5 girls

• 20% of children with DM have Type 2• NAFLD/NASH

o Steatosis in 40% of obese children (Guzzaloni 2000)o Elevated LFTs in 6% of overweight and 10% of obese

kids (Rashid 2000)

Physicians Do not Physicians Do not Address Obesity Address Obesity

Enough:Enough:

• Addressing obesity in the officeo Only 17.4% of 2-5 yr oldo 32.6% of 6-11 yr/oldo 39.6% of 12 -15 yr/oldo 51.6% of 16-19 yr/old

Diabetes Prevention in Diabetes Prevention in Those at RiskThose at Risk

Case 1Case 1• 28 year while male presents with knee pain• Bilateral knee pain, worse as day goes on• No previous workup• No regular PA, computer programmer• No med hx/ family hx of HTN, DM2, CAD• No meds• ROS: admits fatigue, admits weight gain 80 lbs

since college

Case 1 (cont’d)Case 1 (cont’d)• Exam 5’ 10” weight 260 lbs • Stretch marks on abdomen• No synovitis, no swelling, normal ROM, • X-rays are normal

• BP 138/88• FSG 148 non fasting• HgA1c in office 6.0%

Case QuestionsCase Questions• What do you include in your problem list for this

person?• Which do you address first?• What is your treatment plan?

How would you How would you address his weightaddress his weight

• Nothing –he is here for knee pain• Recommend that he start a new diet• Refer him to medical nutrition therapy• Not address it today but get more labs and bring

him back• Start him on a medication• Refer him for weight loss surgery

MedicationsMedications• Which medication would you start?

o Phentermine/topiramate (QnexaR )o Phentermine (AdipexR)o Topiramate (TopamaxR)o Orlistat (ALLIR)o Metformino Amylin (SymlinR)o Exenatide (ByettaR)

Weight Loss SurgeryWeight Loss Surgery• What surgery would you recommend?

o Lipoplastyo Lap-bando Roux-en-Y (gastric by pass)o Gastric sleeveo Biliarypancreatic diversion

Diabetes PreventionDiabetes Prevention

Lifestyle Lifestyle RecommendationsRecommendations

• Reduce total caloric intake• Increase physical activity• Stop sweetened beverages

• What are the specifics and how do you decide which he does?

• What is the motivation to make all of these changes?

Setting Goals for Weight Loss

• Set reasonable goalso 10% weight loss for first 6 monthso 500-1000 calories less/dayo Decrease 1-2 lb/weeko Most patients set goals 2-3 x higher

• Physical activity is importanto More effective in maintaining weight than weight loss

• Resetting goals and diet/exercise is necessary at 6 months and plateaus in weight loss

• Preventing weight gain is an important long-term goal

NHLBI Obesity Education Initiative: A Practical Guide to Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, 2000.

Is there any evidence Is there any evidence that lifestyle changes that lifestyle changes makes a difference to makes a difference to

prevent diabetes?prevent diabetes?

Diabetes PreventionDiabetes Prevention• Diabetes Prevention program• Finnish Diabetes Trail• Da Qing trial

Diabetes Prevention: Lifestyle

Trial Intervention Population Results

Da Qing IGT study

Diet, PA or both

Chinese m/w 45y/o IGT

Each arm decreased DM 31-46%

Finnish DM Prevention

Study

Diet counseling + PA

w/m 55y/o IGT

D + PA decreased DM 58%

Diabetes Prevention Trial

Wt loss + PA

w/m 51y/o IGT

decreased DM 58%

The Finnish Diabetes Prevention Study: Lifestyle The Finnish Diabetes Prevention Study: Lifestyle

Modifications Modifications

0

20

40

60

80

Control (n=250) Diet intervention (n=256)

Inci

den

ce

of

dia

be

tes

(cas

es

/10

00 p

erso

n-y

ears

)

Tuomilehto et al. N Engl J Med. 2001;344:1343.

58%

The Finnish Diabetes Prevention Study:The Finnish Diabetes Prevention Study:

Lifestyle ModificationsLifestyle Modifications

• 522 overweight individuals with IGT randomized to

o Control: diet instruction at the onset of study

o Individualized advice given 7 times in the first year and every 3 months thereafter with goals of

• Weight loss 5%

• Reducing fat intake to <30% of energy consumption

• Increasing fiber intake to 15 g/1000 kcal

• Exercising at a moderate level for 30 min/d

• Primary end point: Prevention of diabetes, as assessed by annual OGTT

Tuomilehto et al. N Engl J Med. 2001;344:1343.

The Finnish Diabetes Prevention Study: Lifestyle The Finnish Diabetes Prevention Study: Lifestyle

Modifications (cont’d)Modifications (cont’d)

-6

-5

-4

-3

-2

-1

0

Weight (kg) Waist (cm) SBP (mm Hg) DBP (mm Hg)

Control (n=250) Diet intervention (n=256)

Ch

an

ge

fro

m b

ase

line

Tuomilehto et al. N Engl J Med. 2001;344:1343.

P<0.001 P<0.001P=0.007 P=0.02

The Diabetes Prevention Program The Diabetes Prevention Program

Sponsored by the NIDDK, NIA, NICHD, NIH, IHS, CDC, Sponsored by the NIDDK, NIA, NICHD, NIH, IHS, CDC, ADA, and other agencies and corporationsADA, and other agencies and corporations

A Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High Risk

Diabetes Prevention Program:Diabetes Prevention Program:

Primary Objectives Primary Objectives

• Compare safety and efficacy of 4 interventions for preventing or delaying development of diabetes o Standard lifestyle recommendations + masked

metformin titrated to 850 mg bid or troglitazone 400 mg/d

o Standard lifestyle recommendations + masked placebo

o Intensive lifestyle intervention by case managers with goals of 7% weight reduction through healthy eating and

physical activity 150 min/wk moderate intensity physical activity

The Diabetes Prevention Program Research Group. Diabetes Care. 1999;22:623.

Diabetes Prevention Program:Diabetes Prevention Program:

Achievement of Study GoalsAchievement of Study GoalsAverage follow-up of 2.8 years

Goal % Achieving Goal

Lifestyle modifications Week 24 Last visitWeight loss 7% 50% 38%Physical activity 150 74% 58%(min/wk)

Pharmacologic intervention Placebo MetforminCompliance 80% 77% 72%Full dose 2 tablets/d 97% 84%

The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.

Diabetes Prevention Program:Diabetes Prevention Program:

Effects on Weight and Dietary IntakeEffects on Weight and Dietary Intake

Lifestyle Placebo Met Inter. P

Value

Wt change (kg) -0.1 -2. -5.6 <0.001

Change in fat intake*(% of total calories)-0.8 -0.8 -6.6 <0.001

Change in energy intake (kcal/d) at 1 year -249-296 -450 <0.001

*Baseline fat intake was 34.1% of total calories. The goal of intensive lifestyle modification was <25% of total calories.

The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.

Diabetes Prevention Program:

Progression to Type 2 Diabetes

0

2

4

6

8

10

12

Placebo Metformin Intensivelifestyle

Ca

ses

/10

0 p

ers

on

-ye

ars

Average follow-up of 2.8 years

31%*

58%*

*All pairwise comparisons significantly different by group; sequential log-rank test.

The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.

Diabetes Treatment in Diabetes Treatment in Obese AdultsObese Adults

Look AHEAD TrialLook AHEAD Trial• Randomized trial 5,145 obese adults diagnosed

with type 2 DMo Randomized to intensive lifestyle intervention

• Goal >7% initial weight loss• 175 minutes per week physical activity

o Outcomes• Fatal MI, CVA, non fatal MI• 11.5 years of follow up

LOOK AHEAD ResultsLOOK AHEAD Results• One year results

o Weight loss 8.6% vs 0.7% (p<0.001)o Fitness improved 20.9% vs 5.8% (p<0.001)o A1c improved 0.7% vs 0.1% (p<0.001)o Lipids, bp, urine albumin/creatinine ratio all improved

(p<0.01)

Look AHEAD: Diabetes Care 2007. 30(6):1374-1383

Medications to Medications to Prevent DiabetesPrevent Diabetes

• Diabetes Prevention Program• Tripod trial/Pipod trial• Stop NIDDM• Xenidos Study

Diabetes Prevention: Medications

Diabetes Prevention Program

TRIPOD STOP- NIDDM

XENIDOS study

Heyms-field et al

Met vs Placebo

Trog. vs. Placebo*

Acarbose vs plac.

Orlistat vs placebo*

Orlistat vs

Placebo*

W/M 51y/o IFG or IGT

Hispanic W 35y/o

Hx GDM

w/m 56y/o IGT

BMI >30 w/m 43y/o

IGT/ norm

w/m 44 y/o

BMI 30-43

Met decr. DM 31%

Trog.decr.

55%*

Acarbose decr. 24%

Orlistat decr. 37%

Orlistat decr. 60%

What works better to What works better to treat diabetes and treat diabetes and

obesity-medications or obesity-medications or surgery?surgery?

Surgery vs Meds in Surgery vs Meds in obese adults with obese adults with

T2DMT2DM• 150 obese adults with type 2 DM

o Intensive medical therapyo Roux-en-Yo Sleeve gastrectomy

• Primary outcomeo % patients with HgA1c < 6%

• Secondary outcomeso Weight losso Lab values

Schauer et al NEJM March 2012

Surgery vs Meds Surgery vs Meds ResultsResults

• Primary outcome achieved at 1 yearo 12% of medication group (p=0.008 vs surgeries)o 37% of sleeve gastectomyo 42% of Roux-en-Y

• Secondary outcomeso Weight loss surgery groups better (p<0.01)

• 24.7-27.5% vs 5.2% (p <0.001)o Reduced medications

• Surgery better (p<0.01)

Schauer et al NEJM March 2012

Surgical Therapies for Obesity

• Restrictive Procedureso Laparoscopic Adjustable Gastric Bandingo Vertical Banded Gastroplastyo Silastic Ring Gastroplastyo Roux-en-Y Gastric Bypass*

• Malabsorptive Procedureso Biliopancreatic Diversiono Duodenal Switcho Roux-en-Y Gastric Bypass*

*Considered both restrictive and malabsorptive

Primary Care Perspective on Bariatric SurgeryMayo Clinic Proceedings, 2004.

Weight Loss SurgeriesWeight Loss Surgeries

Treatment of Combined Treatment of Combined Obesity and DiabetesObesity and Diabetes

Metabolic Effects of Agents

Med SU/ glinide

MET TZD DPP- 4

AGI Colesevelam

Bromocriptine

Wt gain xx xxx

Neutral x x x

Wt loss x x

Metabolic Effects of Metabolic Effects of MedicationsMedicationsGLP-1 RA Amylin Insulin

Weight loss xx x

Neutral

Weight loss xx

SummarySummary• Obesity and type 2 diabetes are intimately

related• Treating obesity can prevent diabetes• Diabetes treatments should be selected with

effects on weight in mind• Aggressive management of weight is important

even once diagnosed with type 2 diabetes• Insulin while necessary in type 1 DM can

contribute to insulin resistance