β-Cell Dysfunction Is Associated with Metabolic Syndrome Severity in Adults

Abstract

Metabolic syndrome is prevalent in adults characterized by increased visceral adiposity and insulin resistance (IR). However, the link between pancreatic β-cell function and metabolic syndrome severity in adults across the glucose spectrum is unknown. We hypothesized that poor β-cell function would independently predict a higher metabolic syndrome Z-score (i.e., severity). Seventy (12 normal glucose tolerant, 37 prediabetic, 21 type 2 diabetic) obese adults [62.4±1.1 year; 34.6±0.6 kg/m(2); data are mean±standard error of the mean (SEM)] participated in this cross-sectional study. A 2-hr 75-gram oral glucose tolerance test (OGTT) was administered, and insulin and glucose area under the curve was determined for calculations of insulin action. Fasting and glucose-stimulated insulin secretion was calculated using homeostasis model assessment of insulin secretion (HOMA-B) and the insulinogenic index (i.e., I(0-30)/Glc(0-30) or I(60-120)/Glc(60-120)), respectively. Fasting and postprandial insulin sensitivity was assessed by HOMA-IR and the Matsuda Index, respectively. β-cell function was estimated using the disposition index via HOMA-B/HOMA-IR, I(0-30)/Glc(0-30) or I(60-120)/Glc(60-120) × Matsuda Index, which represents basal, first-, and second-phase insulin release, respectively. Body composition (via computerized tomography and dual X-ray absorptiometry) and sex-specific metabolic syndrome Z-scores were calculated from waist circumference, blood pressure, fasting glucose, triglycerides, and high-density lipoproteins. Compared to those with normal glucose tolerance, visceral fat and IR were higher and β-cell function was lower in adults with glucose intolerance and type 2 diabetes mellitus. Elevated visceral fat and IR (HOMA-IR and Matsuda Index) correlated with elevated Z-scores (r=0.51, r=0.54, r=-0.49; all P<0.002, respectively). Basal, first-, and second-phase β-cell function correlated with low Z-scores (r=-0.59, r=-0.51, and r=-0.43, all P<0.001). Insulin secretion significantly predicted the Z-score independent of sex, body fat, blood lipids, blood pressure, IR, and glucose metabolism (P<0.005). β-cell dysfunction is highly correlated with the severity of metabolic syndrome in adults. Future work is warranted to elucidate the mechanism by which cardiometabolic disturbances influence insulin secretion.