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Medical Complications of Obesity
BMI-Associated Disease Risk
Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight
and Obesity in Adults—The Evidence Report. Obes Res 1998;6(suppl 2).
Additional risks:
Large waist circumference (men>40 in; women >35 in)
5 kg or more weight gain since age 18-20 y
Poor aerobic fitness
Specific races and ethnic groups
Weight (lb)
Body Mass Index Chart
Relationship Between BMI and Percent Body Fat in Men and Women
Adapted from: Gallagher et al. Am J Clin Nutr 2000;72:694.
Body Fat (%)
Body Mass Index (kg/m2)
0
10
30
40
60
20
50
Women
Men
Pulmonary disease
abnormal function
obstructive sleep apnea
hypoventilation syndrome
Nonalcoholic fatty liver disease
steatosis
steatohepatitis
cirrhosis
Coronary heart disease
Diabetes
Dyslipidemia
Hypertension
Gynecologic abnormalities
abnormal menses
infertility
polycystic ovarian syndrome
Osteoarthritis
Skin
Gall bladder disease
Cancer
breast, uterus, cervix
colon, esophagus, pancreas
kidney, prostate
Phlebitis
venous stasis
Gout
Medical Complications of Obesity
Idiopathic intracranial hypertension
Stroke
Cataracts
Severe pancreatitis
Metabolic Syndrome
Abdominal obesity
Hyperinsulinemia
High fasting plasma glucose
Impaired glucose tolerance
Hypertriglyceridemia
Low HDL-cholesterol
Hypertension
Evolution of Metabolic Syndrome
Isomaa B et al. Diabetes Care. 2001;24:683-689.
AKA: Insulin Resistance Syndrome; Syndrome X; Dysmetabolic Syndrome; Multiple Metabolic Syndrome
1923: Kylin describes clustering of hypertension, gout, and hyperglycemia
1988: Reaven describes “Syndrome X” – hypertension, hyperglycemia, glucose intolerance, elevated triglycerides, and low HDL cholesterol
1998: World Health Organization defines “metabolic syndrome” as clustering of hypertension, low HDL, hypertriglyceridemia, insulin resistance, glucose intolerance or type 2 diabetes, high waist-to-hip ratio, and microalbuminuria
Abdominal obesity
Glucose intolerance/ Insulin resistance
Hypertension
Atherogenic dyslipidemia
Proinflammatory/
Prothrombotic state
Characteristics of the Metabolic Syndrome: NCEP-ATP III
National Cholesterol Educational Program (NCEP), Adult Treatment Panel (ATP) III; 2001.
Diabetes
CVD
Clinical Identification of the Metabolic Syndrome*: NCEP-ATP III
*Diagnosis is established when >3 of these risk factors are present
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
** 2003 New ADA IFG criteria (Diabetes Care)
Increasing Prevalence of NCEP Metabolic Syndrome with Age (NHANES III)
Prevalence (%)
Age
Men Women
Ford E et al. JAMA. 2002;287:356-359.
Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+
CHD Prevalence
No MS/ No DM
8.7%
% of Population = 54.2% 28.7% 2.3% 14.8%
Alexander C, et al. Diabetes 52: 1210-1214, 2003
13.9%
7.5%
19.2%
MS/ No DM
DM/ No MS
DM/ MS
Prevalence of the Metabolic Syndrome Varies by Sex and Race/Ethnicity (NHANES III)
Prevalence (%)
Age
Ford E et al. JAMA. 2002;287:356-359.
25%
16%
28%
21%
23%
26%
36%
20%
Metabolic Syndrome: Impact on Mortality
Mortality Rate (%)
Without metabolic syndrome
With metabolic syndrome
*
Isomaa B et al. Diabetes Care. 2001;24:683-689.
*P < 0.001.
*
Metabolic Syndrome: Impact on Cardiovascular Health
Prevalence (%)
Without metabolic syndrome
With metabolic syndrome
*
*P < 0.001.
Isomaa B et al. Diabetes Care. 2001;24:683-689.
*
*
Elevated Risk of CVD Prior to Clinical Diagnosis of Type 2 Diabetes
Relative Risk
1.00
Nondiabetic throughout the study
Hu FB et al. Diabetes Care. 2002;25:1129-1134.
Prior to diagnosis of diabetes
After diagnosis of diabetes
Diabetic at baseline
2.82
3.71
5.02
Characteristics of Metabolically Normal Obese and Metabolically Abnormal Obese Subjects?
?Postmenopausal women. *P = 0.03; **P = 0.0001. LBM = lean body mass. AT = adipose tissue.
Brochu M et al. J Clin Endocrinol Metab. 2001;86:1020-1025.
Lipids and Lipoproteins & Resting BP in Insulin-Sensitive and Insulin-Resistant Obese Subjects?
?Postmenopausal women. Data are mean ? SD. *P = 0.01.
Brochu M et al. J Clin Endocrinol Metab. 2001;86:1020-1025.
Oral Glucose Tolerance in Insulin-Sensitive and Insulin-Resistant Obese Subjects?
?Postmenopausal women. ?n = 12, sensitive; n = 23, resistant. Data are mean ? SD.
*P = 0.01; **P = 0.005; ***P = 0.001.
Brochu M et al. J Clin Endocrinol Metab. 2001;86:1020-1025.
Waist Size vs BMI and the Metabolic Syndrome
8-y Incidence of Metabolic Syndrome (%)
Waist circumference < level 2*
Waist circumference > level 2*
Han TS et al. Obes Res. 2002;10:923-931.
*Level 2 = waist ?40 inches in men or ?35 inches in women.
9.98
20.45
19.77
33.43
Both Insulin Resistance and Decreased Insulin Secretion Predict the Risk of Developing Type 2 Diabetes: 7-Year Incidence
Percent
Neither Low High
Haffner SM et al. Circulation. 2000;101:975-980.
Insulin secretion Low Low
Insulin resistance High High
Both High Low
Metabolic status HOMA-IR ? I30-0min/?G30-0min
Distribution by Metabolic Status Among Converters to Type 2 Diabetes (83% of Prediabetic Subjects are Insulin Resistant)
Haffner SM et al. Circulation. 2000;101:975-980.
Both (54%)
(n = 195)
Low insulin secretion; insulin sensitive (15.9%)
Neither (1.5%)
Insulin resistant; good insulin secretion (28.7%)
Insulin Resistance (HOMA-IR Quintiles) are Related to CV Disease: San Antonio Heart Study
Increasing Insulin Resistance
A: adjusted for age, sex, and ethnicity
B: adjusted for age, sex, and ethnicity, LDL, triglyceride, HDL, systolic blood pressure, fasting glucose, smoking, alcohol consumption, and leisure time exercise
Hanley A et al. Diabetes Care. 2002;25:1177-1184.
A
HOMA IR
B
Odds Ratio (95% CI)
Increasing Risk of CVD
P (trend) < 0.0001
P (trend) < 0.0075
Intra-Abdominal Fat Mass and CHD Risk in Type 2 Diabetes
Adjusted for BMI, age (continuous), age2, smoking, parental history of myocardial infarction, alcohol consumption, physical activity, menopausal status, hormone replacement therapy, aspirin intake, saturated fat, and antioxidant score.
Rexrode W et al. JAMA. 1998;280:1843-1848.
P < 0.001 for trend.
Ectopic Lipids and the Metabolic Syndrome
Metabolic syndrome reflects failure of intracellular lipohomeostasis, which prevents lipotoxicity in organs of overnourished individuals
Normal individuals: lipohomeostasis (ie, lipid overload confined to white adipocytes, designed to store surplus calories)
Obese individuals: adipocytes increase leptin secretion in an attempt to enhance oxidation of surplus lipid in nonadipocytes
Deficiency or nonresponsiveness to leptin prevents these protective events and results in ectopic accumulation of lipids
Pancreatic ?-cells and myocardiocytes are “cellular victims” – leading to type 2 diabetes and lipotoxic cardiomyopathy
Unger RH. Endocrinology. 2003.
Relationship Between BMI and Cardiovascular Disease Mortality
Relative Risk of Death
Body Mass index
<18.5
Men
Women
Calle et al. N