Abstract

Objective: Most patients with ketosis-prone type 2 diabetes mellitus (KPDM) discontinue insulin therapy and remain in near-normoglycemic remission. This study aimed to determine the effect of glucotoxicity on β-cell function during remission in obese patients with KPDM.

Methods. Age- and BMI-matched obese African-Americans (AA) with history of KPDM (n=8), severe hyperglycemia but without ketosis (ketosis-resistant T2DM, n=7), and obese controls (n=13) underwent intravenous infusion of 10% dextrose at rate 200 mg/m²/min for 20 hours. β-cell function was assessed by changes in insulin and C-peptide concentration during dextrose infusion and by changes in acute insulin response (AIR) and first-phase insulin release (FPIR) to arginine stimulation before and after dextrose infusion.

Results. The mean time to discontinue insulin therapy was 7.1±1.7 weeks in KPDM and 9.6±2.3 weeks in ketosis-resistant T2DM, p=NS. During 20-hr dextrose infusion, changes in insulin, C-peptide and C-peptide/glucose ratio were similar among diabetic and control groups. During dextrose infusion ketosis-resistant T2DM had greater area under curve for blood glucose than KPDM and control subjects, p<0.05. The AIR and FPIR to arginine stimulation as well as glucose potentiation to arginine assessed before and after dextrose infusion were not different among study groups.

Conclusions. Near-normoglycemia remission in obese AA patients with KPDM and ketosis-resistant T2DM is associated with a remarkable recovery in basal and stimulated insulin secretion. At near-normoglycemia remission, KPDM patients displayed a pattern of insulin secretion similar to ketosis-resistant T2DM and obese nondiabetic subjects.