Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity

The simultaneous assessment of quantitative indexes of insulin secretion an d action in a single individual is important when quantifying their relativ e role in the evolution of glucose tolerance in different physiopathologica l states. Available methods quantify these indexes in relatively nonphysiol ogical conditions, e.g., during glucose clamps or intravenous glucose toler ance tests. Here, we present a method based on a physiological test applica ble to large-scale genetic and epidemiologic studies-the oral glucose toler ance test (OGTT). Plasma C-peptide, insulin, and glucose data from a freque ntly sampled OGTT with 22 samples throughout 300 min (FSOGTT(300-22)) were analyzed in 11 subjects with various degrees of glucose tolerance. In each individual, two indexes of pancreatic sensitivity to glucose (Phi (s) [10(9 ) min(-1)] and Phi (d) [10(9)]) and the insulin sensitivity index (S-I) (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 FSOGTT(300-22) were used as a reference f or internal validation of OGTT protocols with reduced sampling schedules. O ur results show that 11 samples in a 300-min period (OGTT(300-11)) is the t est of choice because the indexes it provides (Phi (s) = 36 +/- 3 [means +/ - SE]; Phi (d) = 710 +/- 111; S-I = 10.2 +/- 2.4) show excellent correlatio n and are not statistically different from those of FSOGTT(300-22) (Phi (s) = 33 +/- 3; Phi (d) = 715 +/- 120; S-I = 10.1 +/- 2.3). In conclusion, OGT T(300-11), interpreted with C-peptide and glucose minimal models, provides a quantitative description of beta -cell function and insulin sensitivity i n a single individual while preserving the important clinical classificatio n of glucose tolerance provided by the standard 120-min OGTT.