Oral Glucose Tolerance Test Minimal Model Indexes of -Cell Function and Insulin Sensitivity

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 (FSOGTT300-22) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose ( s [10 9 min] and d [10 ]) and the insulin sensitivity index (SI) (10 5 dl /kg per min per pmol/l) were estimated by using the minimal model of C-peptide secretion and kinetics originally proposed for intravenous graded glucose infusion and the minimal model approach recently proposed for meal/OGTTs. The indexes obtained from FSOGTT300-22 were used as a reference for internal validation of OGTT protocols with reduced sampling schedules. Our results show that 11 samples in a 300-min period (OGTT300-11) is the test of choice because the indexes it provides ( s = 36 ± 3 [means ± SE]; d = 710 ± 111; SI = 10.2 ± 2.4) show excellent correlation and are not statistically different from those of FSOGTT300–22 ( s = 33 ± 3; d = 715 ± 120; SI = 10.1 ± 2.3). In conclusion, OGTT300-11, interpreted with C-peptide and glucose minimal models, provides a quantitative description of -cell function and insulin sensitivity in a single individual while preserving the important clinical classification of glucose tolerance provided by the standard 120-min OGTT. Diabetes 50:150–158, 2001 The 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.