The prevalence of IGT and NIDDM in women with PCOS is substantially higher than expected when compared with age- and weight-matched populations of women without PCOS. The conversion from IGT to NIDDM is accelerated in PCOS. The fasting glucose concentration does not reliably predict the glucose concentration at 2 h after an oral glucose challenge, particularly among those with IGT, the subgroup at highest risk for subsequent development of NIDDM. We conclude that women with PCOS should periodically have an OGTT and must be closely monitored for deterioration in glucose tolerance.

The simultaneous assessment of quantitative indexes of insulin secretion and action in a single individual is important when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Available methods quantify these indexes in relatively nonphysiological conditions, e.g., during glucose clamps or intravenous glucose tolerance tests. Here, we present a method based on a physiological test applicable to large-scale genetic and epidemiologic studies-the oral glucose tolerance test (OGTT). Plasma C-peptide, insulin, and glucose data from a frequently sampled OGTT with 22 samples throughout 300 min (FSOGTT 300-22 ) were analyzed in 11 subjects with various degrees of glucose tolerance. T he simultaneous assessment of ␤-cell function and insulin sensitivity in a single individual is of primary importance when quantifying their relative role in the evolution of glucose tolerance in different physiopathological states. Two methods are available for this purpose: the clamp technique, which uses a euglycemichyperinsulinemic and a hyperglycemic-euinsulinemic clamp in the same individual (1), and the intravenous glucose tolerance test (IVGTT) interpreted by the minimal models of glucose disposal (2) and C-peptide kinetics and secretion (3). Both these approaches give accurate and precise estimates of insulin sensitivity and ␤-cell function in a single individual, but plasma glucose, C-peptide, and insulin concentrations achieved during these studies are relatively nonphysiological. Recently, the need to quantify ␤-cell function and insulin sensitivity under more normal life conditions has encouraged many investigators to use more physiological protocols, including meal-like studies (4), graded up and down glucose infusions (5), meals (6,7), and oral glucose tolerance tests (OGTTs) (8,9). However, an approach to measure indexes of ␤-cell function and insulin action in a single individual based on a physiological test such as the OGTT is not available. The ability to derive in a single individual important information such as the clinical classification of oral glucose tolerance while simultaneously quantifying his or her ␤-cell function and insulin sensitivity could provide a unique tool potentially applicable to large-scale genetic and epidemiologic studies.Therefore, the aim of the present study was to investigate whether indexes of ␤-cell function and insulin sensitivity could be simultaneously assessed in a single individual from OGTT data by extending to the OGTT the up and down C-peptide minimal model (5) and the insulin sensitivity formula recently derived for a meal (7). The database consisted of a frequently sampled 300-min OGTT performed on 11 subjects with various degrees of glucose tolerance. Indexes of insulin sensitivity and ␤-cell function based on OGTTs with reduced number of samples were also calculated and compared with those derived from the frequently sampled OGTT to arrive at a robust clinical protocol. RESEARCH DESIGN AND METHODSSubjects. Studies were ...

No abstract

Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of ␤ cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone ( n ϭ 14) or placebo ( n ϭ 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (S I ) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and ␤ cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% ( P ϭ 0.03) and 39% ( P ϭ 0.003), respectively. S I increased from 1.3 Ϯ 0.3 to 2.6 Ϯ 0.4 ϫ 10 Ϫ 5 min Ϫ 1 pM Ϫ 1 ( P ϭ 0.005). Average insulin secretion rates adjusted for S I over the glucose interval 5-11 mmol/liter were increased by 52% ( P ϭ 0.02), and the ability of the ␤ cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% ( P ϭ 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced ␤ cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance. ( J. Clin. Invest. 1997. 100: 530-537.)