Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.
OBJECTIVE
To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men.


METHODS
Open, uncontrolled, 6-month pilot study. Energy intake was reduced by 30%, and walking for at least 30 min a day was strongly recommended. DZX treatment was started at 50 mg t.i.d. and increased by 50 mg per dose every 4 weeks to a maximum of 300 mg t.i.d., unless hyperglycaemia or other side-effects occurred.


METHODS
Eighteen obese hyperinsulinaemic men with a body mass index of 30-35 kg/m(2). Measurements included body weight, body composition, blood pressure, glycaemic control, insulin response, adiponectin and serum lipids.


RESULTS
Body weight decreased by 9.4 kg (95% CI: 5.6-13.2 kg, p < 0.001), waist circumference reduced by 9.2 cm (95% CI: 5.3-12.9 cm, p < 0.001) and total body fat mass decreased by 23.3% (95% CI: 13.7-32.9%, p < 0.001), without a concomitant change in soft tissue lean body mass or bone mass. Fat loss was inversely related to fasting insulin levels achieved at 6 months (r = -0.76, p < 0.002). Diastolic blood pressure decreased by 10.9 mmHg (95% CI: 6.5-15.4 mmHg, p < 0.002). Fasting and postmeal peak insulin levels were reduced by about 65% (p < 0.001) and decreased to the normal range for non-obese men. Fasting and postmeal peak glucose levels increased by 0.8 +/- 0.3 mmol/l (p = 0.01) and 1.4 +/- 0.7 mmol/l (p = 0.06) respectively. Haemoglobin A1c rose by 0.5% to 5.9 +/- 0.2%.


CONCLUSIONS
High-dose DZX-mediated insulin suppression, in combination with moderate caloric restriction and lifestyle advice, is associated with a clinically relevant degree of weight reduction. A more extensive exploration is warranted to optimize this mode of treatment and to further clarify its risks and benefits.
van Boekel
G
G
Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands.
Loves
S
S
van Sorge
A
A
Ruinemans-Koerts
J
J
Rijnders
T
T
de Boer
H
H
D000328:Adult; D001823:Body Composition / Q000187:drug effects; D031204:Caloric Restriction; D003981:Diazoxide / Q000627:therapeutic use*; D004038:Diet, Reducing; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000097:blood; D007329:Insulin Antagonists / Q000627:therapeutic use*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000178:diet therapy*; D010865:Pilot Projects; D016896:Treatment Outcome; D015431:Weight Loss / Q000502:physiology*
D007328:Insulin; D007329:Insulin Antagonists; D003981:Diazoxide