First-phase insulin response to glucose in nonobese or obese subjects with glucose intolerance: analysis by C-peptide...

This study was proposed to clarify the impairment of first-phase insulin response to glucose in subjects with glucose intolerance by analysis of C-peptide secretion rate after glucose or glucagon injection. The rate was calculated from kinetic analysis of peripheral C-peptide behavior. The rate reached the peak two minutes after glucose injection and then rapidly declined (first-phase secretion) in control subjects. In nonobese subjects with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM), the rate promptly increased in response to glucose and was followed by a second phase increase. The time course of the rate in the subjects was slightly different from that in control subjects. There was a progressively greater deficit in the first-phase increase with increasing severity of glucose intolerance. The time course of the rate in the obese subjects with NIDDM was different from that in control subjects. The first-phase increase was reduced in the obese subjects with NIDDM. The glucose disappearance rate was correlated with the first-phase increase. Since the time course of the rate after glucagon injection in all subjects did correspond well with that in the control subjects, variation of metabolic clearance rate of endogenous C-peptide among the subjects may be negligible for this study. This study provides the precise time course of first- and second-phase insulin response to glucose injection in nonobese and obese subjects with IGT or NIDDM as well as convincing evidence of the progressive reduction of first-phase insulin response with increasing severity of glucose intolerance. First-phase insulin response to glucose might be slightly delayed in some obese subjects with NIDDM.