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Weight loss in obese men by caloric restriction and high‐dose diazoxide–mediated insulin suppression
Author(s) -
Van Boekel G.,
Loves S.,
Van Sorge A.,
RuinemansKoerts J.,
Rijnders T.,
De Boer H.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2008.00878.x
Subject(s) - medicine , endocrinology , insulin , diazoxide , blood pressure , weight loss , body mass index , lean body mass , waist , adiponectin , obesity , insulin resistance , body weight
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.