ASSESSMENT OF INSULIN SENSITIVITY AND SECRETION WITH THE LABELED INTRAVENOUS GLUCOSE-TOLERANCE TEST - IMPROVED MODELING ANALYSIS

A new modelling analysis was developed to assess insulin sensitivity w ith a tracer-modified intravenous glucose tolerance test (IVGTT). IVGT Ts were performed in 5 normal (NGT) and 7 non-insulin-dependent diabet ic (NIDDM) subjects. A 300 mg/kg glucose bolus containing [6,6-H-2(2)] glucose was given at time 0. After 20 min, insulin was infused for 5 m in (NGT, 0.03; NIDDM, 0.05 U/kg). Concentrations of tracer, glucose, i nsulin and C-peptide were measured for 240 min. A circulatory model fo r glucose kinetics was used. Glucose clearance was assumed to depend l inearly on plasma insulin concentration delayed. Model parameters were : basal glucose clearance (Cl-b), glucose clearance at 600 pmol/l insu lin concentration (CI600), basal glucose production (P-b), basal insul in sensitivity index (BSI = Cl-b/basal insulin concentration); increme ntal insulin sensitivity index (ISI = slope of the relationship betwee n insulin concentration and glucose clearance). Insulin secretion was calculated by deconvolution of C-peptide data. Indices of basal pancre atic sensitivity (PSIb) and first (PSI1) and second-phase (PSI2) sensi tivity were calculated by normalizing insulin secretion to the prevail ing glucose levels. Diabetic subjects were found to be insulin resista nt (BSI: 2.3 +/- 0.6 vs 0.76 +/- 0.18 ml . min(-1) . m(-2) . pmol/l(-1 ), p < 0.02; ISI: 0.40 +/- 0.06 vs 0.13 +/- 0.05 ml . min(-1) . m(-1) . pmol/l(-1), p < 0.02; Cl-600: 333 +/- 47 vs 137 +/- 26 ml . min(-1) . m(-2), p < 0.01; NGT vs NIDDM). P-b was not elevated in NIDDM (588 /- 169 vs 606 +/- 123 mu mol . min(-1) . m(-2), NGT vs NIDDM). Hepatic insulin resistance was however present as basal glucose and insulin w ere higher: PSI1 was impaired in NIDDM (67 +/- 15 vs 12 +/- 7 pmol . m in(-1) . m(-2) . mmol/l(-1), p < 0.02; NGT vs NIDDM). In hTGT and in a subset of NIDDM subjects (n = 4), PSIb was inversely correlated with BSI (r = 0.95, p < 0.0001, log transformation). This suggests the exis tence of a compensatory mechanism that increases pancreatic sensitivit y in the presence of insulin resistance, which is normal in some NIDDM subjects and impaired in others. In conclusion, using a simple test t he present analysis provides a rich set of parameters characterizing g lucose metabolism and insulin secretion, agrees with the literature, a nd provides some new information on the relationship between insulin s ensitivity and secretion.