No effect of inhibition of insulin secretion by diazoxide on weight loss in hyperinsulinaemic obese subjects during an 8-week weight-loss diet.
OBJECTIVE
Obesity is positively associated with hyperinsulinaemia, and it has been suggested that hyperinsulinaemia may contribute to maintain the obese state in insulin-resistant obese individuals. The aim of the present study was to investigate the effect of inhibition of insulin secretion by diazoxide on weight loss in obese, normoglycaemic (fasting plasma glucose of > or =6.1 mmol/l), hyperinsulinaemic (fasting plasma insulin of > or =100 pmol/l) adults during a 2.5 MJ/day energy-deficient diet.


METHODS
In an 8-week, double-blind, placebo-controlled parallel design, 35 overweight and obese subjects (age: 23-54 years, body mass index: 27-66 kg/m(2)) were randomized either to 2 mg/kg/day (maximum 200 mg/day) of oral diazoxide or to placebo. Body composition and resting energy expenditure (REE) were measured before and after the intervention. Blood samples, and appetite sensations by visual analogue scales, were collected during fasting, during an oral glucose tolerance test (OGTT) and 4 h postprandially after a test meal. Subsequently, an ad libitum meal was given.


RESULTS
Thirty-one subjects completed the protocol. Eight weeks of diazoxide decreased incremental area under the response curve (iAUC) for insulin (iAUC(insulin)) and for C-peptide (iAUC(C-peptide)) and increased iAUC for glucose (iAUC(glucose)) during the OGTT and the test meal compared with the use of placebo (p < 0.003). No differences in changes between the groups in body weight, body fat, REE or appetite were observed during the 8-week trial.


CONCLUSIONS
These findings do not suggest that hyperinsulinaemia per se contributes to maintenance of the obese state, and insulin secretion inhibition seems not a promising drug target.
Due
A
A
Department of Human Nutrition, The Royal Veterinary and Agricultural University, DK-1958 Frederiksberg C, Denmark. adue@kvl.dk
Flint
A
A
Eriksen
G
G
Møller
B
B
Raben
A
A
Hansen
J B
JB
Astrup
A
A
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003376:Counseling; D003981:Diazoxide / Q000009:adverse effects / Q000627:therapeutic use*; D004038:Diet, Reducing; D004311:Double-Blind Method; D002149:Energy Intake; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000078790:Insulin Secretion; D008297:Male; D009765:Obesity / Q000150:complications / Q000178:diet therapy*; D010352:Patient Dropouts; D010919:Placebos; D014665:Vasodilator Agents / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D007329:Insulin Antagonists; D010919:Placebos; D014665:Vasodilator Agents; D003981:Diazoxide