INSULIN PRODUCTION FOLLOWING INTRAVENOUS GLUCOSE, ARGININE, AND VALINE - DIFFERENT PATTERN IN PATIENTS WITH IMPAIRED GLUCOSE-TOLERANCE AND NON-INSULIN-DEPENDENT DIABETES-MELLITUS

To better understand abnormal insulin production (IP) in states of carbohydrate intolerance, insulin release was quantified following equimolar (2.4 mmol/kg) infusions of glucose, arginine, and valine in healthy subjects ([HS] age, 45 ± 3 years; body mass index [BMI, kg/m2], 26.3 ± 2.4; means ± SEM), obese subjects with impaired glucose tolerance ([IGT] age, 43 ± 5 years; BMI, 35.4 ± 2.4), and non-obese patients with chronic non-insulin-dependent diabetes mellitus ([NIDDM] age, 55 ± 3 years; BMI, 26.4 ± 1.4; duration of disease, 13 ± 3 years). There were eight subjects per group. Incremental IP (metabolic clearance rate of C-peptide [MCRcp] × total incremental area under the curve of plasma C-peptide [AUCcp], pmol/kg) following substrate infusion was as follows: glucose: HS, 227 ± 14; IGT, 1,050 ± 184 (P < .001 v HS); NIDDM, 114 ± 27 (P < .001 v HS); argine: HS, 139 ± 23; IGT, 488 ± 106 (P < .01 v HS); NIDDM, 206 ± 47; and valine: HS, 21 ± 7; IGT, 32 ± 10; NIDDM, 54 ± 12 (P < .01 v HS). The fractional clearance rate ([FCR]k, %/min) was impaired in IGT and NIDDM for glucose (HS, 3.9 ± 0.4; IGT, 2.3 ± 0.3 [P < .01 v HS]; NIDDM, 1.4 ± 0.1 [P < .001 v HS]), arginine (2.4 ± 0.1; 1.9 ± 0.2 [P < .01 v HS]; 1.9 ± 0.2 [P < .01 v HS]), and valine (0.95 ± 0.06; 0.65 ± 0.09 [P < .05 v HS]; 0.74 ± 0.1 [P < .05 v HS]). Thus, incremental IP following glucose, arginine, and valine loading, although consistently increased, displayed the same pattern as in HS (glucose, 100%; arginine, 61%; valine, 9%) in obese patients with IGT, whereas chronic NIDDM was characterized by a qualitative change in insulin release (glucose, 100%; arginine, 180%; valine, 47%). That qualitatively different pattern in stimulated insulin production suggests that IGT and NIDDM represent different modes of carbohydrate intolerance and β-cell dysfunction. © 1994.