Epidemiology of Insulin Resistance, Diabetes Mellitus, and Coronary Heart Disease Steven Haffner, MD
Adapted from World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Geneva: World Health Organization:1999:52.
Criteria for the Diagnosis of Diabetes Mellitus and Hyperglycemia Plasma Glucose Concentration
>7.0 (>126)
>6.1 (>110) to <7.0 (<126)
2-Hour Post Glucose Load
Fasting Glucose
Diabetes Mellitus
Impaired Glucose Tolerance
Impaired Fasting Glucose
>11.1 (>200)
>7.8 (>140) to <11.1 (<200)
Values are mmol/L (mg/dl)
Developed
Developing
Percent
King H et al. Diabetes Care 1998;21:1414-1431.
World
1995
Prevalence of Diabetes in Adult Population (Aged >20 years) by Year and Region
2000
2025
Hospitalization Costs for Chronic Complications of Diabetes in the US
American Diabetes Association. Economic Consequences of Diabetes Mellitus in the US in 1997. Alexandria, VA: American Diabetes Association, 1998:1-14.
Total costs 12 billion US $
CVD accounts for 64% of total costs
Others
Ophthalmic disease
Cardiovascular disease
Renal disease
Neurologic disease
Peripheral vascular disease
Annual CHD Deaths per 1000 Persons
Kannel WB, McGee DL. JAMA 1979;241:2035-2038.
Framingham Study: DM and CHD Mortality 20-Year Follow-up
17
8
17
4
Men
Women
DM
Non-DM
Ischemic heart disease
% of Deaths
Geiss LS et al. In: Diabetes in America. 2nd ed. 1995; chap 11.
Mortality in People with Diabetes Causes of Death
Other heart disease
Diabetes
Cancer
Stroke
Infection
Other
Mortality per 1000 person-years*
*Age-adjusted
Adapted from Gu K et al. Diabetes Care 1998;21:1138-1145.
Mortality Due to Heart Disease in Men and Women with or without Diabetes (US)
29.9
19.2
Men
Women
Diabetes
No Diabetes
All heart disease
Ischemic heart disease
Men
Women
11.5
6.3
23.0
7.1
11.0
3.6
Nondiabetes
Diabetes
*Defined in 1971-1975, followed up through 1982-1984. **Defined in 1982-1984, followed up through 1992-1993.
Gu K et al. JAMA 1999;281:1291-1297.
Trends in Mortality Rates for Ischemic Heart Disease in NHANES Subjects with and without Diabetes*
17.0
6.8
-16.6%
+10.7%
Men, cohort 1*
Men, cohort 2**
Women, cohort 1*
Women, cohort 2**
-43.8%
-20.4%
14.2
7.6
7.4
4.2
2.4
1.9
(P=0.46)
(P=0.76)
(P<0.001)
(P=0.12)
Rate per 1000 person-years
WOMEN
MEN
Survival Post-MI in Diabetic and Nondiabetic Men and Women: Minnesota Heart Survey
Adapted from Sprafka JM et al. Diabetes Care 1991;14:537-543.
100
80
60
40
0
Survival (%)
Months Post-MI
No diabetes
n=228
n=1628
Months Post-MI
Survival (%)
0
20
40
60
Diabetes
100
80
60
40
0
80
0
20
40
60
80
Diabetes
No diabetes
n=156
n=568
WOMEN
MEN
Cardiovascular Mortality in People with Diabetes
% of Deaths (Crude Rate)
Adapted from Miettinen H et al. Diabetes Care. 1998;21:69-75.
Diabetes
No Diabetes
28.6
22.1
10.9
11.9
Diabetes
No Diabetes
15.4
9.6
22.7
9.0
9.1
4.2
11.1
2.8
28 d – 1 y
Hospitalization – 28 d
Out of Hospital
Influence of Multiple Risk Factors* on CVD Death Rates in Diabetic and Nondiabetic Men: MRFIT Screenees
None
One only
Age-adjusted CVD death rate per 10,000 person-years
*Serum cholesterol >200 mg/dl, smoking, SBP >120 mmHg
Stamler J et al. Diabetes Care 1993;16:434-444
All three
No diabetes
Diabetes
Two only
Putative Mechanism for Increased Atherosclerosis in Type 2 Diabetes
BLACK BOX
Dyslipidemia
Hypertension
Hyperinsulinemia/insulin resistance
Hemostatic abnormalities
Hyperglycemia
AGE proteins
Oxidative stress
AGE = advanced glycation end products
Adapted from Bierman EL. Arterioscler Thromb 1992;12:647-656.
+ = moderately increased compared with nondiabetic population
++ = markedly increased compared with nondiabetic population
– = not different compared with nondiabetic population
Prevalence of Cardiovascular Risk Factors in Diabetic Subjects Relative to Nondiabetics
Type 1
Dyslipidemia Hypertriglyceridemia Low HDL Small, dense LDL Increased apo B
Hypertension
Hyperinsulinemia/insulin resistance
Central obesity
Family history of atherosclerosis
Cigarette smoking
Adapted from Chait A, Bierman EL. In: Joslin’s Diabetes Mellitus. Philadelphia: Lea & Febiger, 1994:648-664.
Type 2
Risk Factor
+
–
–
–
+
–
–
–
–
++
++
++
++
++
++
++
+
–
Differences in HDL Cholesterol and LDL Size by Diabetic Status in Women and Men
Howard BV et al. Diabetes Care 1998; 21:1258-1265.
0
-2
-4
-6
-8
Differences between participants with and without diabetes
HDL Cholesterol
LDL Size
?
0
-2
-4
-6
-8
mg/dL
Women
Men
Women
Men
Strategies for Reduction of Diabetic Complications
Microvascular complications - Aggressive screening - Improved metabolic control
Macrovascular complications - Improved glycemic control (positive but minor) - Prevention of type 2 diabetes - Aggressive treatment of established CVRF in diabetic and possibly prediabetic subjects - Diabetic agents that improve cardiovascular risk
Incidence Rates of MI and Microvascular Endpoints by Mean Systolic Blood Pressure: UKPDS
110
120
130
140
150
160
170
Incidence per 1000 Person Years (%)
Adler AI et al. BMJ 2000;321:412-419.
Updated Mean Systolic Blood Pressure (mmHg)
Adjusted for age, sex, and ethnic group
Myocardial Infarction
Microvascular Endpoints
Incidence Rates of MI and Microvascular Endpoints by Mean Hemoglobin A1c: UKPDS
5
6
7
8
9
10
11
Incidence per 1000 Person Years (%)
Stratton IM et al. BMJ 2000;321:405-412.
Updated Mean Hemoglobin A1c Concentration (%)
Adjusted for age, sex, and ethnic group
Myocardial Infarction
Microvascular Endpoints
Plasma Insulin and Triglycerides Predict Ischemic Heart Disease: Quebec Cardiovascular Study
Despres JP et al. N Engl J Med 1996;334:952-957.
Odds Ratio
<12
12-15
>15
F-Insulin (?U/ml)
4.6
p=0.005
>150 mg/dl
<150 mg/dl
Triglycerides
1.0
1.5
5.3
p=0.001
P<0.001
6.7
5.4
P=0.002
Plasma Insulin and Apolipoprotein B Predict Ischemic Heart Disease: Quebec Cardiovascular Study
Despres JP et al. N Engl J Med 1996;334:952-957.
Odds Ratio
<12
12-15
>15
F-Insulin (?U/ml)
3.0
p=0.04
>119 mg/dl
<119 mg/dl
Apolipoprotein B
1.0
1.5
3.2
p<0.001
11.0
9.7
P<0.001
p=0.04
LDL Particle Size and Apolipoprotein B Predict Ischemic Heart Disease: Quebec Cardiovascular Study
Lamarche B et al. Circulation 1997;95:69-75.
>25.64
<25.64
LDL Peak Particle Diameter (nm)
1.0
1.0
6.2
(p<0.001)
Apo B
>120 mg/dl
2.0
<120 mg/dl
Baseline Anthropometric Variables and Cardiovascular Risk Factors in Subjects with Normal Glucose Tolerance at Baseline According to Conversion Status at 8-Year Follow-up: San Antonio Heart Study
BMI (kg/m2)
Centrality*
TG (mmol)
HDLC (mmol)
SBP (mmHg)
Fasting glucose (mmol)
Fasting insulin (pmol)
Haffner SM et al. JAMA 1990;263:2893-2898.
28.2 + 1.