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

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.

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

“…[1][2][3] Modan et al 4 suggested that there is a relationship between insulin levels and blood pressure, and several groups have hypothesized that insulin resistance and/or hyperinsulinemia contribute to the pathogenesis of hypertension. 5,6 Thus, insulin has an important role in pathophysiological regulation of the cardiovascular system.…”

Hypertension, hyperinsulinaemia and obesity in middle-aged Finns with impaired glucose tolerance

“…Christlieb et al 5 found a causal relationship between the level of circulating insulin and diastolic BP at the first-year follow-up of subjects with impaired glucose tolerance. Haffner et al 11 observed an independent association in subjects with normal body weight and normoglycaemia. A causal relationship between the elevated fasting insulin concentration and the development of hypertension was found in this study.…”

“…One prospective study revealed that after adjustment for overweight and body fat distribution, fasting insulin was an independent risk factor for hypertension only in subjects with normal body weight and normoglycaemia, 11 whereas another study showed that changes in blood pressure (BP) preceded abnormal glucose tolerance, but not hyperinsulinaemia. 4 A study made on non-obese young adult black men with the euglycaemic hyperinsulinaemic clamp technique suggested that insulin resistance might precede the onset of established essential hypertension.…”

Comparison of indices of insulin resistance with metabolic syndrome classifications to predict the development of impaired fasting glucose in overweight and obese subjects: a 3-year prospective study

“…10 More recently, an index incorporating fasting insulin and triglyceride levels, the McAuley index, has also been shown to be a sensitive marker of IR 11 and has attracted increasing use in clinical research. The presence of the metabolic syndrome (MetS) itself is also often used as a surrogate marker of IR, 12 with its characteristic abnormalities of a raised triglyceride (trig) to highdensity lipoprotein (HDL)-cholesterol ratio (trig:HDL) 13 and low circulating levels of the insulin-sensitizing adipocytokine, adiponectin, [14][15][16] shown to correlate with the degree of IR.…”