Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM

Abstract

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.