Framingham Offspring Study - CVD Risk, Resistance, Met. Syndrome
The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMA-IR) and by Gutt et al.'s insulin sensitivity index (ISI0,120). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age- and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5–2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2–2.9], P = 0.003; and for ISI0,120 [both highest versus lowest quartile]: 0.5 [0.3–0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI0,120 levels were independently related to incident CVD (0.5 [0.3–0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8–2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P ≤ 0.007 in both). In conclusion, metabolic syndrome and ISI0,120 but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance.
The National Cholesterol Education Program (NCEP) definition of the metabolic syndrome was proposed as a practical tool for identifying a high-risk cardiovascular disease (CVD) phenotype, and several studies have subsequently confirmed that the metabolic syndrome predicts incident CVD. The metabolic syndrome may also serve as a surrogate measure of the insulin resistance phenotype as it identifies a proportion of subjects with insulin resistance without directly measuring insulin action.
Insulin resistance may be causally related to increased CVD risk. Direct measurement of insulin resistance using the hyperinsulinemic-euglycemic clamp has practical limitations; consequently, data linking directly measured insulin resistance with CVD is derived mostly from cross-sectional studies and rarely from prospective cohorts.
Fasting insulin is a simple indirect measure of insulin resistance. Prospective studies using this measure have been equivocal or modest with regard to CVD risk. Of the remaining indirect measures of insulin resistance, the homeostasis model assessment formula (HOMA-IR), requiring only fasting glucose and insulin measurements, is the most popular. HOMA-IR values correlate reasonably well with "gold standard" clamp-derived values. Recently, Gutt et al. proposed an index of insulin sensitivity (ISI0,120) that uses glucose and insulin levels before and after oral glucose loading. ISI0,120 values correlate well with directly measured insulin resistance and have been shown to predict incident diabetes. Most but not all studies have shown an association of the more sophisticated indirect measures of insulin resistance with CVD.
It is not known if the NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) definition of the metabolic syndrome identifies all the CVD risk associated with insulin resistance. We therefore studied baseline metabolic syndrome and two surrogate insulin resistance measures, HOMA-IR and ISI0,120, and their independent relation to 7-year CVD risk in the Framingham Offspring Study cohort.
The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMA-IR) and by Gutt et al.'s insulin sensitivity index (ISI0,120). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age- and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5–2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2–2.9], P = 0.003; and for ISI0,120 [both highest versus lowest quartile]: 0.5 [0.3–0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI0,120 levels were independently related to incident CVD (0.5 [0.3–0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8–2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P ≤ 0.007 in both). In conclusion, metabolic syndrome and ISI0,120 but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance.
The National Cholesterol Education Program (NCEP) definition of the metabolic syndrome was proposed as a practical tool for identifying a high-risk cardiovascular disease (CVD) phenotype, and several studies have subsequently confirmed that the metabolic syndrome predicts incident CVD. The metabolic syndrome may also serve as a surrogate measure of the insulin resistance phenotype as it identifies a proportion of subjects with insulin resistance without directly measuring insulin action.
Insulin resistance may be causally related to increased CVD risk. Direct measurement of insulin resistance using the hyperinsulinemic-euglycemic clamp has practical limitations; consequently, data linking directly measured insulin resistance with CVD is derived mostly from cross-sectional studies and rarely from prospective cohorts.
Fasting insulin is a simple indirect measure of insulin resistance. Prospective studies using this measure have been equivocal or modest with regard to CVD risk. Of the remaining indirect measures of insulin resistance, the homeostasis model assessment formula (HOMA-IR), requiring only fasting glucose and insulin measurements, is the most popular. HOMA-IR values correlate reasonably well with "gold standard" clamp-derived values. Recently, Gutt et al. proposed an index of insulin sensitivity (ISI0,120) that uses glucose and insulin levels before and after oral glucose loading. ISI0,120 values correlate well with directly measured insulin resistance and have been shown to predict incident diabetes. Most but not all studies have shown an association of the more sophisticated indirect measures of insulin resistance with CVD.
It is not known if the NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) definition of the metabolic syndrome identifies all the CVD risk associated with insulin resistance. We therefore studied baseline metabolic syndrome and two surrogate insulin resistance measures, HOMA-IR and ISI0,120, and their independent relation to 7-year CVD risk in the Framingham Offspring Study cohort.