ELEVATED RATIO OF SUMMED SERUM PROINSULIN TO INSULIN-RESPONSE AFTER ORAL GLUCOSE-LOAD IN TYPE-2 DIABETES DECREASES FOLLOWING SULFONYLUREA TREATMENT

We showed previously that the disproportionate elevation of serum proi nsulin at fasting and after glucose ingestion in Type 2 diabetes is re duced to nearly normal after improvement of glycemic control by diet t herapy. In this study, we investigated the effect of sulfonylurea (SU) treatment on serum proinsulin levels and proinsulin/insulin ratio (PI /I) during oral glucose tolerance test in patients with Type 2 diabete s. Thirteen diabetic patients (age 56 +/- 9 years, body mass index 22. 4 +/- 1.9 kg/m(2), mean +/- SD) were examined by 75 g oral glucose tol erance test (OGTT) before and after glycemic control by SU therapy. Me an interval of two OGTTs was 126 days. Serum proinsulin was measured b y the radioimmunoassay using a human proinsulin-specific antiserum. Wh en glycemic control improved after SU therapy (mean fasting plasma glu cose 11.5 and 6.0 mmol/l, before and after SU treatment), fasting insu lin, proinsulin and PI/I ratio did not change significantly. Insulin r esponse during OGTT markedly increased after SU therapy. Summed value of insulin (Sigma I) increased from 634 to 1064 pmol/l after SU (P < 0 .01), whereas summed proinsulin (Sigma PI) did not change significantl y (146 and 159 pmol/l), resulting a significant decrease in Sigma PI/S igma I (23.6-15.1%, P < 0.05). We conclude that the disproportionate e levation of proinsulin during OGTT in patients with Type 2 diabetes ca n be reduced after glycemic control by SU treatment, chiefly by a sele ctive increase in insulin response.