Progressive deterioration of beta-cell function in nonobese type 2 diabetic subjects. Postprandial plasma C-peptide...

The purpose of the present study was to characterize secondary failure (SF) to oral hypoglycaemic agents by assessment of threshold insulin-secretion values in relation to diabetes duration. One hundred and forty-seven nonobese diabetic patients, 35 to 80 years of age, with disease duration ranging from 1 to 36 years, were studied. Beta-cell function was assessed by meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations. The quality of glycaemic control was considered good if mean daily blood glucose was less than 8.5 mmol/l. One group with good (NOb-GC) and another with poor control (NOb-SF) were established. Mean daily glycaemia was negatively correlated with delta CP or delta aCP (r = -0.703 vs r = -0.696; p < 0.001) more than with basal C-peptide (r = -0.453; p < 0.001). A close positive correlation between meal-stimulated (delta CP) and glucagon-stimulated (delta aCP) C-peptide concentrations was observed (r = 0.869; p < 0.001). Residual beta-cell function (delta CP and delta aCP) was significantly correlated with known disease duration in both groups (GC: r = -0.693 and SF: r = -0.680; p < 0.001). Nonobese patients with SF showed early impaired secretion during the first years of disease, meal-stimulated delta CP being below 0.350 mmol/l. The most useful result in this study was the incremental value of C-peptide (delta CP), which showed minimal overlapping between the two groups. Basal, postprandial or postglucagon absolute values were less discriminating. The daily profile allowed measurement of both glycaemic control and insulin production after a regular meal. The validity of this measurement was confirmed by the strong correlation between meal-stimulated and glucagon-stimulated delta C-peptide concentrations. This parameter is a useful physiological marker of secondary failure.