Individuals with prediabetes display different age-related pathophysiological characteristics.

CONTEXT: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are highly pathophysiologic heterogeneous prediabetes conditions encompassing from youth to elderly people. OBJECTIVE: Herein we evaluate whether distinct age-related phenotypes exist among individuals with IFG or IGT. RESEARCH DESIGN: 479 young (aged 18-35 years), 699 adult (45-55 years) and 240 older (≥65 years) subjects underwent an oral glucose tolerance test (OGTT). Based to the OGTT, study participants were grouped as follows: normal glucose tolerant (NGT) young subjects (Y-NGT), NGT adults (A-NGT), NGT older subjects (O-NGT), IFG young subjects (Y-IFG), IFG adult individuals (A-IFG), IFG older subjects (O-IFG), IGT young subjects (Y-IGT), IGT adults (A-IGT), and IGT older individuals (O-IGT). MAIN OUTCOME MEASURES: Insulin sensitivity and secretion, insulin clearance and β-cell function. RESULTS: Peripheral insulin sensitivity assessed by Matsuda index, basal and glucose-stimulated insulin secretion, and β-cell function estimated by the disposition index were decreased in A-IFG and O-IFG compared to Y-IFG. A-IGT and Y-IGT individuals exhibited a progressively higher degree of hepatic insulin resistance assessed by liver IR index, and reduced insulin clearance compared to O-IGT. Conversely, Matsuda index did not differ between Y-IGT, A-IGT and O-IGT. Basal and glucose-stimulated insulin secretion, and β-cell function were lower in A-IGT and O-IGT subjects compared to Y-IGT individuals. CONCLUSIONS: Subjects with IFG or IGT exhibit different age-related pathophysiologic characteristics. A more precise phenotyping of subjects with IGT or IFG could help to better design individualized preventive approaches to counteract diabetes progression.