Impact of traits of metabolic syndrome on β-cell function and insulin resistance in normal fasting, normal glucose tolerant subjects

Objective: Metabolic syndrome, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT) predict risk for type 2 diabetes mellitus (T2DM). To determine if increased risk preceded development of these abnormalities, β-cell function and insulin resistance were assessed in euglycemic subjects with and without traits of metabolic syndrome. Methods: A total of 562 apparently healthy Latin-American subjects were screened for metabolic syndrome [National Education Cholesterol Program Adult Treatment Panel III (NECP ATP III)]. Early pancreatic insulin response ΔInsulin0-30/ ΔGlucose0-30, Matsuda index, disposition index (DI), and homeostasis model assessment of insulin resistance (HOMA-IR) ratio were obtained from oral glucose tolerance testing (0-180 min). Results: ΔI 0-30/ΔG0-30, Matsuda index, DI, and HOMA-IR deteriorated in direct proportion with number of traits of metabolic syndrome, and with increases in glucose levels within the euglycemic range. DI was the most sensitive index. In subjects with 1, 2, 3, and 4-5 traits, DI was 21.4%, 40%, 57%, and 76% lower, respectively, than in subjects with no traits. As a single trait, abdominal obesity was associated with insulin resistance, whereas, low high-density lipoprotein cholesterol (HDL-C), alone or combined with high triglycerides, was not associated with insulin resistance or β-cell dysfunction. Combined impairments in β-cell function and insulin sensitivity were responsible for the increases in fasting and 2-h plasma glucose concentrations within the euglycemic range. Conclusions: Impaired β-cell function and increased insulin resistance are present much before development of metabolic syndrome, IFG, or IGT. β-Cell function and insulin sensitivity worsen in direct proportion with number of traits of metabolic syndrome and increases in glucose levels. Compared to abdominal obesity, low HDL-C±high triglycerides may bear a lesser weight in predicting risk of T2DM.