natural history of obesity leading to type 2 diabetes genetic susceptibility environmental factors...
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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
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Obesity Trends* Among U.S. Adults (BMI ≥ 30 or ≈ 30 lbs overweight for 5’4” woman)
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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
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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???
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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
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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
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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
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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.
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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
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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
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Link Between Obesity and Type 2 Diabetes: Nurses’ Health Study
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Surgery for Severe Obesity: US 1992 to 2003 NEJM March 11, 2004
Number of Bariatric Surgeries 1992-2003
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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
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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
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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
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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
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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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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)
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Age Specific Prevalence of DM 2002
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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
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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
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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).
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Major Birth Defects:Preexisting Type I vs Type II Diabetes
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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
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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 < 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
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Majority of Patients with Diabetes are Not at ADA HbA1c Goal <7%
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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)
WorldWorld 2003 = 194 million2003 = 194 million 2025 = 333 million2025 = 333 million
Increase 72%Increase 72%
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Age Adjusted Prevalence of CVD 1997-2002
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End Stage Renal Disease 1984-2001
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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.
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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
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-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
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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
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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
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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
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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
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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
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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