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


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.
Guldstrand
M
M
Division of Internal Medicine, Karolinska Institutet, Danderyd Hospital, Stockholm. marie.guldstrand@med.ds.sll.se
Grill
V
V
Björklund
A
A
Lins
P E
PE
Adamson
U
U
D000959:Antihypertensive Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003981:Diazoxide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity; D011384:Proinsulin / Q000097:blood; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
D000959:Antihypertensive Agents; D001786:Blood Glucose; D002096:C-Peptide; D002784:Cholesterol; D008078:Cholesterol, LDL; D003981:Diazoxide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D011384:Proinsulin; D014280:Triglycerides