Individuation of different metabolic phenotypes in normal glucose tolerance test.

Based on the hypothesis that a more efficient glucose utilization lowers the risk of progression to type 2 diabetes, we tested the capability of oral glucose tolerance test (OGTT) to identify subjects at risk included inside normal glucose tolerance (NGT). We measured fasting and 2-h plasma glucose (FPG and 2hPG) and insulin values (FPI and 2hPI) in 623 normal OGTTs. Insulin sensitivity and secretion were computed with HOMA2 method and Stumvoll's formula. Secretion was expressed as HOMA2%beta, first (1stPH) and second-phase (2ndPH) insulin release. The percentage increment of 2hPG with respect to FPG (PG%) was used to subdivide patients into PG% tertiles, considered as the primary grouping variable. Covariance analysis (ANCOVA) for multiple comparisons was performed considering the above measurements as dependent variables, sex, age, body mass index (BMI) and waist circumference as covariates. In subjects with PG% < or =0, we documented significant increments of insulin sensitivity and significant decrements of resistance and secretion compared to subjects with PG% >0. ANCOVA disclosed that insulin sensitivity fell, while 1stPH secretion rose significantly from the lower to the higher tertile of PG%. OGTT may be useful to establish NGT as well as a more subtle metabolic phenotype. The closer 2hPG is to FPG, the higher insulin sensitivity and the lower insulin secretion are. The stimulus to maintain NGT elicits more insulin secretion, predisposing to worsening glucose tolerance when a faltering insulin secretion ensues. These subjects could benefit from prospective prevention treatment and studies.