Diet only or diet and sulfonylureas in mild type II diabetes (NIDDM)? Pathophysiologic and therapeutic implications

Abstract

Plasma glucose, insulin and C-peptide responses to a test meal were studied in 7 nonobese patients with type II diabetes mellitus (NIDDM) treated with diet alone and after 6 months of gliclazide therapy, as well as in 6 matched controls. The glycemic levels were significantly higher (p less than 0.05) in patients under diet alone than in controls and after gliclazide treatment (peak: 12.8 +/- 1.0; 7.9 +/- 0.4 and 10.0 +/- 0.5 mmol/l, respectively; means +/- SEM). Diet and gliclazide treated patients showed a reduced B-cell response during the first hour after the meal as indicated by insulin and C-peptide values and areas (insulin areas 0-60 min: controls 57.9 +/- 10.9; p less than 0.01 vs diet alone 14.2 +/- 2.7 and vs gliclazide 22.1 +/- 2.8 microU/ml/min). The hypoinsulinemic phase lasted from 20 to 60 min before gliclazide, and from 20 to 45 min after gliclazide. The first significant C-peptide increase, detected at 10 min in controls and at 30 min under diet alone, was advanced to 15 min after gliclazide treatment.

In conclusion: patients with mild, diet-treated NIDDM show a sluggish and attenuated B-cell response to a physiologic challenge (test meal); this secretory impairment is present even after a complete post-prandial glycemic normalization, supporting the idea of a persistent defect. Nevertheless, the slight improvement observed in insulin secretion after gliclazide treatment may be promoting, at least partially, the normalization of prandial hyperglycemia. The benefits of this normalization in diabetic patients previously controlled by diet only await further investigation.