Prospective Analysis of The Insulin-Resistance Syndrome (Syndrome X)

TLDR

Hyperinsulinemia and insulin resistance are linked to hypertension, dyslipidemia, and type 2 diabetes, a cluster termed Syndrome X, yet prior cross‑sectional studies could not determine whether insulin resistance causes these disorders. The study examined how fasting insulin predicts the 8‑year incidence of metabolic abnormalities in the San Antonio Heart Study, a population‑based cohort of Mexican Americans and non‑Hispanic whites. Higher fasting insulin predicted the 8‑year onset of hypertension, low HDL, high triglycerides, and type 2 diabetes, remained significant after adjusting for obesity, and was higher in those who later developed multiple metabolic disorders, supporting that insulin resistance precedes the metabolic syndrome.

Abstract

Many studies have shown that hyperinsulinemia and/or insulin resistance are related to various metabolic and physiological disorders including hypertension, dyslipidemia, and non-insulin-dependent diabetes mellitus. This syndrome has been termed Syndrome X. An important limitation of previous studies has been that they all have been cross sectional, and thus the presence of insulin resistance could be a consequence of the underlying metabolic disorders rather than its cause. We examined the relationship of fasting insulin concentration (as an indicator of insulin resistance) to the incidence of multiple metabolic abnormalities in the 8-yr follow-up of the cohort enrolled in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease in Mexican Americans and non-Hispanic whites. In univariate analyses, fasting insulin was related to the incidence of the following conditions: hypertension, decreased high-density lipoprotein cholesterol concentration, increased triglyceride concentration, and non-insulin-dependent diabetes mellitus. Hyperinsulinemia was not related to increased low-density lipoprotein or total cholesterol concentration. In multivariate analyses, after adjustment for obesity and body fat distribution, fasting insulin continued to be significantly related to the incidence of decreased high-density lipoprotein cholesterol and increased triglyceride concentrations and to the incidence of non-insulin-dependent diabetes mellitus. Baseline insulin concentrations were higher in subjects who subsequently developed multiple metabolic disorders. These results were not attributable to differences in baseline obesity and were similar in Mexican Americans and non-Hispanic whites. These results support the existence of a metabolic syndrome and the relationship of that syndrome to multiple metabolic disorders by showing that elevations of insulin concentration precede the development of numerous metabolic disorders.