Improved beta cell function after short-term treatment with diazoxide in obese subjects with type 2 diabetes

Diabetes Metab. 2002 Dec;28(6 Pt 1):448-56.

Abstract

Objective: Our aim was to distinguish beneficial effects of B-cell rest from other effects of correction of hyperglycaemia. For this purpose we used diazoxide which reversibly blocks insulin secretion.

Material and methods: Eight obese (age 53 +/- 1 yr: BMI 33 +/- 2 kg/m2: 4 females) type 2 diabetic patients with poor metabolic control (HbA1c 8.7 +/- 0.9% ref.<5.2%) were studied twice after a randomly ordered treatment period of five days of intensive i.v. insulin treatment alone or i.v. insulin with peroral diazoxide (300 mg/day, divided into 3 doses). The glycaemic control was not altered between the two treatment periods. Insulin secretion was measured in response to i.v. glucose and arginine.

Results: Insulin infusion was used to achieve close to identical degrees of glycaemia during the two treatment periods. Previous treatment with diazoxide was associated with a moderate 1.9 +/- 0.6 fold rise in insulin response to intravenous glucose (p=0.04) and 1.6 +/- 0.4 fold increased glucose potentiation of arginine-induced insulin secretion (GPAIS) (p=0.04). Conversely, after insulin alone there was no response to i.v. glucose and no change in GPAIS.

Conclusions: Short-term diazoxide treatment improved important parameters of B-cell function and these effects could be dissociated from confounding effects of changes in glycaemia. Consequently, the results indicate beneficial effects of B-cell rest.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • C-Peptide / blood
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diazoxide / therapeutic use*
  • Drug Therapy, Combination
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Infusions, Intravenous
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin / therapeutic use*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Middle Aged
  • Obesity*
  • Proinsulin / blood
  • Regression Analysis
  • Triglycerides / blood

Substances

  • Antihypertensive Agents
  • Blood Glucose
  • C-Peptide
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Triglycerides
  • Proinsulin
  • Cholesterol
  • Diazoxide