Lack of lipotoxicity effect on {beta}-cell dysfunction in ketosis-prone type 2 diabetes.

Abstract

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.

• Authors: Guillermo E Umpierrez, Dawn Smiley, Gonzalo Robalino, Limin Peng, Aidar R Gosmanov, Abbas E Kitabchi
• Journal: Diabetes care (Diabetes Care) Vol. 33 Issue 3 Pg. 626-31 (Mar 2010) ISSN: 1935-5548 [Electronic] United States
• PMID: 20028938 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fat Emulsions, Intravenous
• Hypoglycemic Agents
• Insulin
• Arginine

Topics

• Adult
• Arginine (pharmacology)
• Diabetes Mellitus, Type 2 (complications, therapy)
• Diabetic Ketoacidosis (physiopathology, therapy)
• Drug Administration Schedule
• Fat Emulsions, Intravenous (administration & dosage, adverse effects)
• Female
• Humans
• Hypoglycemic Agents (administration & dosage)
• Insulin (administration & dosage)
• Insulin-Secreting Cells (drug effects, pathology, physiology)
• Male
• Middle Aged
• Obesity (complications, physiopathology)
• Pancreatic Function Tests (methods)
• Remission Induction
• Withholding Treatment