Metabolic control analysis (MCA) of intravenous glucose tolerance in healthy humans.

We recently assessed 1st and 2nd phase ß-cell insulin secretion by applying the same model of glucose-induced insulin secretion to plasma glucose and C-peptide curves during both IVGTTs and hyperglicemic clamps. In the present study we have extended the same modeling strategy to standard OGTT (time 0’-120’). We performed in 31 subjects (18 with normal glucose regulation [NGR], 7 with impared glucose regulation [IGR], and 6 with newly diagnosed type 2 diabetes [T2DM]) a standard OGTT (blood samples for plasma glucose/C-peptide were collected every 5’-20’ from 0’ to 120’), and an IVGTT (12 g per m2 of BSA; blood samples collected every 1’-20’ from 0’ to 180’-240’) on 2 separate day. We have applied the same modeling strategy to both tests and obtained a fairly good fit of the data in both the IVGTT and the OGTT. We thus estimated first (1st) and second (2nd) phase insulin secretion during both tests. Results are normalized per m2 of BSA. In the pooled data, OGTT 1st and 2nd (2996±299 e 96.1±7.37, respectively) were significantly higher (p<0.01) than IVGTT 1st and 2nd (467±67 e 43.8±4.3), reflecting the well known potentiating effect of oral glucose on -cell response. Moreover, OGTT 1st and 2nd were positively and significantly correlated to IVGTT 1st and 2nd (r=0.50 e r=0.52, respectively; p<0.01 for both). Finally, in NGR, IGR and T2DM subjects OGTT 1st (3609±430, 2439±437 e 1807±220) and 2nd (112±9.5, 80.8±13 e 66.2± 11.5, respectively) showed a similar declining pattern as the one observed with the IVGTT (624±83, 427±112 and 42.8±27.8 for IVGTT 1st; 44.8±6.5, 48.3±9.1 and 35.5±5 for IVGTT 2nd, respectively). These data demonstrate that is feasible to assess 1st and the 2nd insulin secretion phase during a standard OGTT and provide a physiological tool to measure ß-cell function in states of normal and/or altered glucose regulation.