Lack of Lipotoxicity Effect on β-Cell Dysfunction in Ketosis-Prone Type 2 Diabetes

Objective: Over half of newly diagnosed obese African-Americans (AA) with diabetic ketoacidosis (DKA) discontinue insulin therapy and go through a period of near-normoglycemia remission. This subtype of diabetes is known as ketosis-prone type 2 diabetes (KPDM). Methods. To investigate the role of lipotoxicity on β-cell function, 8 obese AA with KPDM, 8 obese subjects with type 2 diabetes with severe hyperglycemia without ketosis (ketosis-resistant T2DM), and 9 nondiabetic obese controls underwent intravenous infusion of Intralipid 20% at 40 ml/hr for 48 hours. β-cell function was assessed by changes in insulin and C-peptide concentration during infusions and by changes in acute insulin response to arginine stimulation (AIRarg) before and after lipid infusion. Results. The mean time to discontinue insulin therapy was 11.0±8.0 weeks in KPDM and 9.6±2.2 weeks in ketosis-resistant T2DM, p=NS. At remission, KPDM and ketosis-resistant T2DM had similar glucose (94±14 vs. 109±20 mg/dl), A1C (5.7±0.4 vs. 6.3±1.1 %), and baseline AIRarg response (34.8±30 vs. 64±69 μU/ml), p= NS. Despite a four-fold increase in FFAs levels (0.4±0.3 to 1.8±1.1 mmol/l, p<0.01) during the 48-hour Intralipid infusion, the response to AIRarg stimulation, as well as changes in insulin and C-peptide levels were similar among obese patients with KPDM, ketosis-resistant T2DM and nondiabetic controls. 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. A high FFAs level by Intralipid infusion for 48 hours was not associated with β-cell decompensation (lipotoxicity) in KPDM patients.