R. Alemzadeh et al., BENEFICIAL EFFECT OF DIAZOXIDE IN OBESE HYPERINSULINEMIC ADULTS, The Journal of clinical endocrinology and metabolism, 83(6), 1998, pp. 1911-1915
Hyperinsulinemia, insulin resistance, and increased adipose tissue are
hallmarks of the obesity state in both humans and experimental animal
s. The role of hyperinsulinemia as a possible preceding event in the d
evelopment of obesity has been proposed. We previously demonstrated th
at administration of diazoxide (DZ), an inhibitor of insulin secretion
, to obese hyperinsulinemic Zucker rats resulted in less weight gain,
enhanced insulin sensitivity, and improved glucose tolerance. Assuming
that hyperinsulinemia plays a major role in the development of human
obesity, then its reversal should have therapeutic potential. To test
this hypothesis, we conducted a randomized placebo-controlled trial in
24 hyperinsulinemic adults [body mass index (BMI) > 30 kg/m(2)]. All
subjects were placed on a low-calorie (1260 for females and 1570 for m
ales) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week
lead-in period, 12 subjects (mean +/- SE for age and BMI, 31 +/- 1 an
d 40 +/- 2, respectively) received DZ (2 mg/kg BW-day; maximum, 200 mg
/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean +/- SE
for age and BMI, 28 +/- 1 and 43 +/- 1, respectively) received placebo
. Compared with the placebo group, DZ subjects had greater weight loss
(9.5 +/- 0.69% vs. 4.6 +/- 0.61%, P < 0.001), greater decrease in bod
y fat (P < 0.01), greater increase in fat-free mass to body fat ratio
(P < 0.01), and greater attenuation of acute insulin response to gluco
se (P < 0.01). However, there was no significant difference in insulin
sensitivity and glucose effectiveness, as determined by the insulin-m
odified iv glucose tolerance test (Bergman's minimal model) and no sig
nificant difference in glycohemoglobin values. Conclusion: 8 weeks tre
atment with DZ had a significant antiobesity effect in hyperinsulinemi
c obese adults without inducing hyperglycemia.