METABOLIC-CLEARANCE RATE OF INSULIN IN TYPE-2 DIABETIC-PATIENTS TREATED WITH COMBINED INSULIN AND SULFONYLUREA THERAPY

The metabolic clearance rate of insulin (MCR(I)) in 10 non-obese type 2 diabetic patients treated with either insulin alone or combined insu lin plus sulfonylurea therapy is investigated. A classical 2-hour eugl ycaemic hyperinsulinaemic glucose clamp using the artificial pancreas was performed in a randomized order after two 6-week periods of treatm ent: either with subcutaneous injections of insulin alone or with insu lin plus oral administration of the sulfonylurea compound glipizide at the dose of 3 x 10 mg/day. The MCR(I) was calculated knowing the cons tant insulin infusion rate (0.1 U.kg-1.h-1) and measuring basal and st eady-state plasma free insulin and C-peptide levels. When the test was performed at the end of the period of treatment with insulin plus gli pizide and 30 min after the ingestion of the last dose of 10 mg glipiz ide, plasma C-peptide levels were significantly increased and steady-s tate free insulin levels tended to be slightly higher whereas the meta bolic clearance rate of glucose was not affected. The MCR(I) was signi ficantly reduced by glipizide from 23.3 +/- 2.9 to 18.9 +/- 2.0 ml.kg- 1.min-1 p<0.05. These results demonstrate that the sulfonylurea glipiz ide decreases the MCR(I). This effect may play a role in the hypoglyce mic action of sulfonylureas.