Lack of lipotoxicity effect on {beta}-cell dysfunction in ketosis-prone type 2 diabetes.
OBJECTIVE Over half of newly diagnosed obese African Americans 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). RESEARCH DESIGN AND METHODS To investigate the role of lipotoxicity on beta-cell function, eight obese African Americans with KPDM, eight obese subjects with type 2 diabetes with severe hyperglycemia without ketosis (ketosis-resistant type 2 diabetes), and nine nondiabetic obese control subjects underwent intravenous infusion of 20% intralipid at 40 ml/h for 48 h. beta-Cell function was assessed by changes in insulin and C-peptide concentration during infusions and by changes in acute insulin response to arginine stimulation (AIR(arg)) 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 type 2 diabetes (P = NS). At remission, KPDM and ketosis-resistant type 2 diabetes had similar glucose (94 +/- 14 vs. 109 +/- 20 mg/dl), A1C (5.7 +/- 0.4 vs. 6.3 +/- 1.1%), and baseline AIR(arg) response (34.8 +/- 30 vs. 64 +/- 69 microU/ml). P = NS despite a fourfold increase in free fatty acid (FFA) levels (0.4 +/- 0.3 to 1.8 +/- 1.1 mmol/l, P < 0.01) during the 48-h intralipid infusion; the response to AIR(arg) stimulation, as well as changes in insulin and C-peptide levels, were similar among obese patients with KPDM, patients with ketosis-resistant type 2 diabetes, and nondiabetic control subjects. CONCLUSIONS Near-normoglycemia remission in obese African American patients with KPDM and ketosis-resistant type 2 diabetes is associated with a remarkable recovery in basal and stimulated insulin secretion. A high FFA level by intralipid infusion for 48 h was not associated with beta-cell decompensation (lipotoxicity) in KPDM patients.
Umpierrez
Guillermo E
GE
Department of Medicine, Emory University, Atlanta, Georgia, USA. geumpie@emory.edu
Smiley
Dawn
D
Robalino
Gonzalo
G
Peng
Limin
L
Gosmanov
Aidar R
AR
Kitabchi
Abbas E
AE
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000628:therapy*; D016883:Diabetic Ketoacidosis / Q000503:physiopathology / Q000628:therapy*; D004334:Drug Administration Schedule; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D010186:Pancreatic Function Tests / Q000379:methods; D012074:Remission Induction; D028761:Withholding Treatment
D005217:Fat Emulsions, Intravenous; D007004:Hypoglycemic Agents; D007328:Insulin; D001120:Arginine