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

Abstract

We recently assessed 1st and 2nd phase f-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\u2019-120\u2019). 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\u2019-20\u2019 from 0\u2019 to 120\u2019), and an IVGTT (12 g per m2 of BSA; blood samples collected every 1\u2019-20\u2019 from 0\u2019 to 180\u2019-240\u2019) 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 (\uf0731st) and second (\uf0732nd) phase insulin secretion during both tests. Results are normalized per m2 of BSA. In the pooled data, OGTT \uf0731st and \uf0732nd (2996\ub1299 e 96.1\ub17.37, respectively) were significantly higher (p<0.01) than IVGTT \uf0731st and \uf0732nd (467\ub167 e 43.8\ub14.3), reflecting the well known potentiating effect of oral glucose on \uf062-cell response. Moreover, OGTT \uf0731st and \uf0732nd were positively and significantly correlated to IVGTT \uf0731st and \uf0732nd (r=0.50 e r=0.52, respectively; p<0.01 for both). Finally, in NGR, IGR and T2DM subjects OGTT \uf0731st (3609\ub1430, 2439\ub1437 e 1807\ub1220) and \uf0732nd (112\ub19.5, 80.8\ub113 e 66.2\ub1 11.5, respectively) showed a similar declining pattern as the one observed with the IVGTT (624\ub183, 427\ub1112 and 42.8\ub127.8 for IVGTT \uf0731st; 44.8\ub16.5, 48.3\ub19.1 and 35.5\ub15 for IVGTT \uf0732nd, 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 f-cell function in states of normal and/or altered glucose regulation