Natural History of Obesity Leading to Type 2 Diabetes

1
Natural History of Obesity Leading to Type 2
Diabetes
Complications
Onset ofdiabetes
Disability
Genetic susceptibility Environmental
factors Nutrition Physical inactivity
IGT
Ongoing hyperglycemia
Obesity Insulin resistance
Death
Risk for Disease
AtherosclerosisHyperglycemiaHypertension
RetinopathyNephropathyNeuropathy
BlindnessRenal failureCHDAmputation
Metabolic Syndrome
2
Obesity Trends Among U.S. Adults (BMI 30 or
30 lbs overweight for 54 woman)
3
Prevalence () of overweight among children and
adolescents
Average 11 year old boy today is 11 pounds
heavier than in 1973
4
National Longitudinal Survey of Youth Prospective
Cohort Study of 8270 Children (4-12 years old) -
1999

• Risk of Overweight Overweight
• gt 85th ile BMI gt 95th ile BMI
• African American 38.4 21.5
• Hispanics 37.9 21.8
• Caucasian 25.8 12.3

Source NHANES???
5
Secular Increases in Relative Weight and
Adiposity in Children (5-14 years old)- Bogalusa
Heart Study -
Change adjusted for height, age, race, and
sex Source Pediatrics 99420-426, 1997
6
Correlations of Weight and BMI in Youth at 7.7
and 23.6 Years
r0.605
r0.612
Source Minneapolis Childrens BP Study,
Circulation 991471, 1999
7
Relationship Between Prevalence of Overweight and
Daily TV Hours
Gortmaker et al., 1996
8
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 p0.054)
• Ate more fast food (1.4 vs. 1.1/week p0.051)
• 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 Childrens Healthy Eating and
  Exercise Practices Survey. The California
  Endowment. Rev. August 2002.

9
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
10
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 lt 85th percentile 0.1
• Based on 1994 population estimates, 910,000
  adolescents had metabolic syndrome.

Source Cook et al., Arch Pediatr Adolesc Med
157821-827, 2003
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Link Between Obesity and Type 2 Diabetes Nurses
Health Study
12
Number of Bariatric Surgeries 1992-2003
Surgery for Severe Obesity US 1992 to 2003
NEJM March 11, 2004
13
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 50,000
Source NIDDK
Highest Increase Rate of all Pediatric Surgeries
14
Natural History of Obesity Leading to Type 2
Diabetes
Complications
Onset ofdiabetes
Disability
Genetic susceptibility Environmental
factors Nutrition Physical inactivity
IGT
Ongoing hyperglycemia
Obesity Insulin resistance
Death
Risk for Disease
AtherosclerosisHyperglycemiaHypertension
RetinopathyNephropathyNeuropathy
BlindnessRenal failureCHDAmputation
Metabolic Syndrome
15
Type 2 DiabetesA Progressive Disease
Impaired glucose tolerance (IGT)
Undiagnosed diabetes
Known diabetes
Insulin resistance
Insulin secretion
Postprandial glucose
Fasting glucose
Microvascular complications
Macrovascular complications
Adapted from Ramlo-Halsted BA, Edelman SV. Prim
Care. 199926771-789
16
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/2002

Mokdad, et al, JAMA 2001 286,1195
17
Diabetes and Gestational Diabetes Trends Among
Adults in the United States, Behavioral Risk
Factor Surveillance System, 1990, 1995 and 2001
1990
1993
2001
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Prevalence of Diabetes

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Diabetes Prevalence Among Minority Populations
in the U.S.
Percentage of each population with diabetes
Non-Hispanic Whites
Latinos
African Americans
7.8 (11.4 million)
13 (2.8 million)
10.2 (2 million)
15.1 (105,000)
Native Americans Alaska Natives
?
Centers for Disease Control and Prevention (CDC)
1999 www.cdc.gov/diabetes

20
Age Specific Prevalence of DM 2002
21
The Changing Face of Diabetes in Youth
Source Fagot-Campagna et al., J Pediatr
136664-672, 2000
22
Diabetes Projected RisksFor Babies Born in 2000

• Girls 38 lifetime risk
• If diabetic before age 40, Lifespan shortened by
  14 years (Quality of life by 19 years)
• Boys 33 lifetime risk
• If diabetic before age 40, Lifespan shortened by
  12 years. (Quality of life by 22 years)

V Narayan et al JAMA 8 Oct 2003
23
Prevalence of Diabetes in Pregnancyin the United
States of America

• More than 135,000 GDM 200,000 T2DM
• 6,000 T1DM pregnancies annually

American Diabetes Association. Diabetes Care.
199821(Suppl. 2).
24
Major Birth DefectsPreexisting Type I vs Type
II Diabetes
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ADA Goals for Glycemic Control

• A1C lt 7.0
• Pre-prandial plasma 90-130 mg/dl
• glucose
• Peak postprandial lt180 mg/dl
• plasma glucose
• Referenced to a non-diabetic range of
  4.0-6.0 using a DCCT-based assay

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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 lt 7.0 43 (gt9.5, 18)
• LDL lt 100 11 (gt130, 58)
• BP lt 140/90 66
• Dilated eye exam 63
• Foot exam 55

Natl Health Nutrition Exam Survey
Behavioral Risk Factors Surveillance Study
27
Majority of Patients with Diabetes are Not at ADA
HbA1c Goal lt7
28
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
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GLOBAL PROJECTIONS FOR THE DIABETES EPIDEMIC
2003-2025 (millions)
World 2003 194 million 2025 333
million Increase 72
30
Age Adjusted Prevalence of CVD 1997-2002
31
End Stage Renal Disease 1984-2001
32
Coronary Heart Disease Mortality in Type 2
Diabetes
Men
Women
60
60
Diabetes
Diabetes

50
50
No Diabetes
No Diabetes
40
40
Mortality Rate per 1000
Mortality Rate per 1000
30
30
20
20
10
10
0
0
0-3
4-7
8-11
12-15
16-19
20-23
0-3
4-7
8-11
12-15
16-19
20-23
Duration of Follow-up (yr)
Duration of Follow-up (yr)
Krowlewski AS, et al Am J Med 1991 90
(suppl2A)56S-61S.
33
A1C Predicts CV Risk in Type 2 DiabetesKuusisto
et al
229 Finnish Patients Followed for 3.5 Years
CHD mortality
All CHD events
Incidence () over 3.5 years


Lowlt6
Middle6.07.9
Highgt7.9
Lowlt6
Middle 6.07.9
Highgt7.9
A1C tertile
CHDcoronary heart disease Plt0.01 vs lowest
tertile Plt0.05 vs lowest tertile
Kuusisto J et al. Diabetes. 199443960-967
34
UKPDS - Glycemic Control Risk Reductions
35
UKPDS - BP Control Risk Reductions
Any Diabetes Related Endpoint
Deaths Related to Diabetes
24 Risk Reduction
32 Risk Reduction
Events/ 1000 pt-years
p0.0046
p0.0019
n1148
UKPDS. BMJ 1998 317 703-713
36
4S Study Effect of Simvastatin on Coronary
Events - 6 years
37
Prevention of T2D withLifestyle
Intervention(N523 with IGT, mean age 55, BMI 31)
Incidence of diabetes reduced 58 (p.0003).
diet, exercise, frequent visits yearly advice
Source Tuomilehto et al., ADA 2000
38
Type 2 Diabetes Prevention
Percent developing diabetes

All participants
All participants
Risk reduction 31 by metformin 58 by lifestyle
Placebo
40
30
Metformin
Cumulative incidence ()
20
Lifestyle
10
0
0

1

2

3

4
Years from randomization
The DPP Research Group, NEJM 346393-403, 2002
39
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

Source James et al., Brit Med J 3281237, 2004
40
Natural History of Obesity Leading to Type 2
Diabetes
Complications
Onset ofdiabetes
Disability
Genetic susceptibility Environmental
factors Nutrition Physical inactivity
IGT
Ongoing hyperglycemia
Obesity Insulin resistance
Death
Risk for Disease
AtherosclerosisHyperglycemiaHypertension
RetinopathyNephropathyNeuropathy
BlindnessRenal failureCHDAmputation
Metabolic Syndrome