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. DESIGN: 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. SUBJECTS AND 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%. CONCLUSION: 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.

High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment.

BACKGROUND: Obesity can be associated with biochemical evidence of isolated hypogonadotropic hypogonadism (IHH) in men. Prevalence and severity of IHH in obese men are not exactly known. OBJECTIVE: To assess the prevalence of IHH in obese men. DESIGN AND SUBJECTS: Cross-sectional study of 160 obese men, BMI >30 kg/m2, who applied for medical or surgical treatment of obesity in a general teaching hospital. MAIN OUTCOME MEASURES: Total and calculated free testosterone (TT and FT) in relation to body mass index (BMI). RESULTS: Mean age of the study population was 43.3 +/- 0.8 years (mean +/- SEM), BMI ranged from 30.0 to 65.7 kg/m2. TT and FT levels were inversely related to BMI (-0.48, p<0.0001). Total testosterone was subnormal in 57.5% and free testosterone in 35.6% of the subjects. The group of men with IHH was more obese, had higher Hba IC levels and had a 2.6 higher risk for cardiovascular disease. Decreased libido and erectile dysfunction were 7.1 and 6.7 times as common in IHH than in eugonadal obese men. CONCLUSION: Reduced T levels, well into the hypogonadal range, are common in male obesity. Assessment of its clinical implications, and a search for the best mode of treatment are warranted.