natural history of obesity leading to type 2 diabetes genetic susceptibility environmental factors...

Natural History of Obesity Leading to Type 2 Diabetes

Genetic susceptibilityEnvironmental factors

NutritionPhysical inactivity

AtherosclerosisHyperglycemiaHypertension

RetinopathyNephropathyNeuropathy

BlindnessRenal failureCHDAmputation

Onset ofdiabetes

Complications

Disability

DeathOngoing hyperglycemiaIGTObesity Insulin resistance

Risk forDisease Metabolic

Syndrome

Obesity Trends* Among U.S. Adults (BMI ≥ 30 or ≈ 30 lbs overweight for 5’4” woman)

0

2

4

6

8

10

12

14

16

1963-70 1971-74 1976-80 1988-94 1999-2000

6-11 years

12-19 years

Prevalence (%) of overweight among

children and adolescentsAverage 11 year old boy today is 11 pounds heavier than in 1973

National Longitudinal Survey of Youth Prospective Cohort Study of 8270 Children (4-12 years old) - 1999

Risk of Overweight Overweight

> 85th %ile BMI > 95th %ile BMI

African American 38.4% 21.5%

Hispanics 37.9% 21.8%

Caucasian 25.8% 12.3%Source: NHANES???

Secular Increases in Relative Weight and Adiposity in Children (5-14 years old)

- Bogalusa Heart Study -

Study yearsWeight

(kg)Height (cm)

BMI (kg/m2)

1973-1974 35.9 140 17.6

1992-1994 41.0 142 19.5

Change* +3.4 +1.6 +1.5

* Change adjusted for height, age, race, and sexSource: Pediatrics 99:420-426, 1997

Correlations of Weight and BMI in Youth at 7.7 and 23.6 Years

Source: Minneapolis Children’s BP Study, Circulation 99:1471, 1999

r=0.605 r=0.612

Relationship Between Prevalence of Overweight and Daily TV Hours

0

5

10

15

20

25

30

35

0-2Hours

2-3Hours

3-4Hours

4-5Hours

>5Hours

% Overweight

Gortmaker et al., 1996

Overweight Children

• Ate fewer fruits and vegetables (2.9 vs. 3.3/day)• Drank more sweetened beverages (1.3 vs. 1.1/day)• Ate more high-fat snacks (64 vs. 56 %; p=0.054)• Ate more fast food (1.4 vs. 1.1/week; p=0.051)• Spent more screen time (101 vs. 81 minutes)• Less likely take part in lessons on nutrition (50 vs. 64 percent).

Special Report on Policy Implications from the 1999 California Children’s Healthy Eating and Exercise Practices Survey. The California Endowment. Rev. August 2002.

Pediatric Overweight AAP Policy Statement

• Identify and track at risk youth• Calculate and plot BMI yearly• Promote health eating patterns

– Fruits, vegetables, low-fat dairy, whole grains– Self-regulation of intake, limits on choices, modeling

• Promote physical activity• Limit TV and video• Monitor changes in obesity-associated risk

factors (BP, lipids, IGT, apnea, hyperinsulinism)

Source: Pediatrics 112, August 2003

Metabolic SyndromePrevalence in 12-19 Year Olds

• Overall 4.2% (6.1% M, 2.1% F)– BMI 95th percentile 28.0%– BMI 85th-94th percentile 6.8%– BMI < 85th percentile 0.1%

Based on 1994 population estimates, 910,000 adolescents had metabolic syndrome.

Source: Cook et al., Arch Pediatr Adolesc Med 157:821-827, 2003

Link Between Obesity and Type 2 Diabetes: Nurses’ Health Study

Surgery for Severe Obesity: US 1992 to 2003 NEJM March 11, 2004

Number of Bariatric Surgeries 1992-2003

GI Surgery for Severe Obesity

Risk and Complications:

• 10-20% require follow-up surgery

• Abdominal hernia

• Break down of staple line

• Gallstones

• 30% develop nutritional deficiency

Cost: $20,000 to $50,000Source: NIDDK

Highest Increase Rate of all Pediatric Surgeries

Natural History of Obesity Leading to Type 2 Diabetes

Genetic susceptibilityEnvironmental factors

NutritionPhysical inactivity

AtherosclerosisHyperglycemiaHypertension

RetinopathyNephropathyNeuropathy

BlindnessRenal failureCHDAmputation

Onset ofdiabetes

Complications

Disability

DeathOngoing hyperglycemiaIGTObesity Insulin resistance

Risk forDisease Metabolic

Syndrome

Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789

Type 2 DiabetesA Progressive Disease

Macrovascular complicationsMicrovascular complications

Insulin resistanceInsulin resistance

ImpairedImpairedglucose tolerance glucose tolerance

(IGT)(IGT)UndiagnosedUndiagnosed

diabetesdiabetes Known diabetesKnown diabetes

Insulin secretion Insulin secretion Postprandial Postprandial glucoseglucoseFasting glucoseFasting glucose

Burden of Diabetes in USA

• 18.2 Million Americans Have Diabetes

• 5.2 Million Unaware of Diagnosis

• 40 Million Americans Have Prediabetes

• 239,000 Diabetes-Related Deaths/year

• 2-to-6-Fold More Likely to Have Heart Disease

• 2-to-4-Fold More Likely to Have a Stroke

• 75% of All Diabetes Related Deaths Associated With Cardiovascular Disease

• Cost $132 Billion/2002Mokdad, et al, JAMA 2001 286,1195

Diabetes and Gestational Diabetes Trends Among Adults in the United States, Behavioral Risk Factor Surveillance System, 1990, 1995 and 2001

1990 1993

2001

Prevalence of Diabetes

0

5

10

15

20

7.80% 10.20% 13% 15.10%

Non-Hispanic Whites

Latinos

African Americans

Native Americans & Alaska Natives

Diabetes Prevalence Among Minority Populations in the U.S.

Centers for Disease Control and Prevention (CDC) 1999 www.cdc.gov/diabetes

Percentage of each population with diabetes

7.8% (11.4 million)

10.2% (2 million)

13% (2.8 million)

15.1% (105,000)

Age Specific Prevalence of DM 2002

The Changing Face of Diabetes in Youth

0

5

10

15

20

25

30

35

% w

ith

typ

e 2

87 88 89 90 91 92 93 94 95 96

Cincinnati <19 years Little Rock 8-21 yearsSan Antonio <19 years

Source: Fagot-Campagna et al., J Pediatr 136:664-672, 2000

Diabetes Projected Risks:

For Babies Born in 2000

Girls: 38% lifetime risk

o If diabetic before age 40, Lifespan shortened by 14 years (Quality of life by 19 years)

Boys: 33% lifetime risko If diabetic before age 40,

Lifespan shortened by 12 years. (Quality of life by 22 years)

V Narayan et al: JAMA 8 Oct 2003

Prevalence of Diabetes in Pregnancyin the United States of America

•More than 135,000 GDM + 200,000 T2DM

+ •6,000 T1DM

pregnancies annually

Diabetes8%

Non-diabetes92%

American Diabetes Association. Diabetes Care. 1998;21(Suppl. 2).

Major Birth Defects:Preexisting Type I vs Type II Diabetes

ADA Goals for Glycemic Control

• A1C < 7.0%*• Pre-prandial plasma 90-130 mg/dl

glucose• Peak postprandial <180 mg/dl

plasma glucose

*Referenced to a non-diabetic range of 4.0-6.0% using a DCCT-based assay

Diabetes Care in the U.S.Improvement Needed

• Data from NHANES III* and BRFSS**• Participants 18-74 years with DM• Results: Percent at Goal

–A1C < 7.0 43% (>9.5, 18%)–LDL < 100 11% (>130, 58%)–BP < 140/90 66%–Dilated eye exam 63%–Foot exam 55%

* Nat’l Health & Nutrition Exam Survey** Behavioral Risk Factors Surveillance Study

Majority of Patients with Diabetes are Not at ADA HbA1c Goal <7%

Census Bureau Projections

2000-2050• Census Bureau projects population will

grow 47% by 2050

• By 2050, there will be 112% more diagnosed cases of diabetes

• Serious diabetes complications are projected to increase 137-189% by 2050

Diabetes 50 (Suppl 2): A205, 2001

GLOBAL PROJECTIONS FOR THE DIABETES EPIDEMIC: 2003-2025 (millions)

WorldWorld 2003 = 194 million2003 = 194 million 2025 = 333 million2025 = 333 million

Increase 72%Increase 72%

Age Adjusted Prevalence of CVD 1997-2002

End Stage Renal Disease 1984-2001

Coronary Heart DiseaseMortality in Type 2 Diabetes

0

10

20

30

40

50

60

0-3 4-7 8-11 12-15 16-19 20-23

Duration of Follow-up (yr)

Mo

rtal

ity

Rat

e p

er 1

000

0

10

20

30

40

50

60

0-3 4-7 8-11 12-15 16-19 20-23

Duration of Follow-up (yr)

Mo

rtal

ity

Rat

e p

er 1

000

Diabetes

No Diabetes

Men Women

Diabetes

No Diabetes

Krowlewski AS, et al Am J Med 1991; 90 (suppl2A):56S-61S.

0

5

10

15

20

25CHD mortality All CHD events

A1C tertileCHD=coronary heart disease*P<0.01 vs lowest tertile; †P<0.05 vs lowest tertile

Kuusisto J et al. Diabetes. 1994;43:960-967

Low<6%

Middle6.0%–7.9%

High>7.9%

Low<6%

Middle 6.0%–7.9%

High>7.9%

*

†Incidence (%) over 3.5 years

A1C Predicts CV Risk in Type 2 DiabetesKuusisto et al

0

5

10

15

20

25

229 Finnish Patients Followed for 3.5 Years

-12

-25

-29

-24

-33

-16

-46-50

-45

-40

-35

-30

-25

-20

-15

-10

-5

0Any Diabetes

RelatedEndpoint

MicrovascularEndpoints

Laser Rx Cataract Albuminuria MyocardialInfarction

Sudden Death

% Risk Reduction Lancet 1998; 352: 837-853

UKPDS - Glycemic Control Risk Reductions

UKPDS - BP Control Risk Reductions

67.4

50.9

20.313.7

0

20

40

60

80

Less Tight Tight Less Tight Tight

n=1148

p=0.0046

24%Risk Reduction

32%Risk Reduction

Ev

ents

/ 10

00 p

t-y

ears

UKPDS. BMJ 1998 317: 703-713

p=0.0019

Any Diabetes Related Endpoint Deaths Related to Diabetes

4S Study: Effect of Simvastatin on Coronary Events - 6 years

45

2327

19

0

10

20

30

40

50

Placebo Simvastatin Placebo Simvastatin

Diabetic Diabetic PatientsPatientsn=201, p=0.002n=201, p=0.002

Nondiabetic Nondiabetic PatientsPatientsn=4242, p<0.00001n=4242, p<0.00001

55%55%Risk ReductionRisk Reduction 32%32%

Risk ReductionRisk Reduction

% of Patients with a Major Coronary Event

Pyorala et al, Diabetes Care 1997; 20: 614

Prevention of T2D withLifestyle Intervention

(N=523 with IGT, mean age 55, BMI 31)

Weight Loss (kg) Cases

1st year 2nd year 4th year

Intervention* -4.2 -3.5 26 (10%)

Control** -0.8 -0.8 57 (22%)

Source: Tuomilehto et al., ADA 2000

Incidence of diabetes reduced 58% (p=.0003).

* diet, exercise, frequent visits ** yearly advice

0 1 2 3 4

0

10

20

30

40

Percent developing diabetes

All participants

All participants

Years from randomization

Cu

mu

lativ

e in

cid

enc

e (

%)

Placebo

Metformin

Lifestyle

Type 2 Diabetes Prevention

Risk reduction31% by metformin58% by lifestyle

The DPP Research Group, NEJM 346:393-403, 2002

School-based Program to Decrease Soda Consumption

• 644 children (7-11 years old), 6 schools• Program to decrease regular and diet soda

intake delivered in 1-hour sessions 4 times per year

# Glasses of Soda Per Day

% Overweight and Obese

Intervention 0.6 0.2

Control 0.2 7.5

Source: James et al., Brit Med J 328:1237, 2004

Natural History of Obesity Leading to Type 2 Diabetes

Genetic susceptibilityEnvironmental factors

NutritionPhysical inactivity

AtherosclerosisHyperglycemiaHypertension

RetinopathyNephropathyNeuropathy

BlindnessRenal failureCHDAmputation

Onset ofdiabetes

Complications

Disability

DeathOngoing hyperglycemiaIGTObesity Insulin resistance

Risk forDisease Metabolic

Syndrome