van Boekel G, Loves S, van Sorge A, Ruinemans-Koerts J, Rijnders T, de Boer H
Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands.
Diabetes Obes Metab. 2008 Dec;10(12):1195-203. doi: 10.1111/j.1463-1326.2008.00878.x. Epub 2008 May 12.
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.
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.
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.
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%.
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.
探讨大剂量二氮嗪（DZX）介导的胰岛素抑制作用，联合适度热量限制和增加体力活动，能否使肥胖的高胰岛素血症男性体重减轻至少15%这一概念。
开放、非对照的6个月试点研究。能量摄入减少30%，并强烈建议每天步行至少30分钟。DZX治疗起始剂量为50mg，每日3次，每4周每剂量增加50mg，最大剂量为每日3次300mg，除非出现高血糖或其他副作用。
18名体重指数为30 - 35kg/m²的肥胖高胰岛素血症男性。测量指标包括体重、身体成分、血压、血糖控制、胰岛素反应、脂联素和血脂。
体重下降9.4kg（95%置信区间：5.6 - 13.2kg，p < 0.001），腰围减少9.2cm（95%置信区间：5.3 - 12.9cm，p < 0.001），全身脂肪量减少23.3%（95%置信区间：13.7 - 32,9%，p < 0.001），而软组织瘦体重或骨量无相应变化。脂肪减少与6个月时达到的空腹胰岛素水平呈负相关（r = -0.76，p < 0.002）。舒张压下降10.9mmHg（95%置信区间：6.5 - 15.4mmHg，p < 0.002）。空腹和餐后峰值胰岛素水平降低约65%（p < 0.001），降至非肥胖男性的正常范围。空腹和餐后峰值血糖水平分别升高0.8±0.3mmol/L（p = 0.01）和1.4±0.7mmol/L（p = 0.06）。糖化血红蛋白升高0.5%至5.9±0.2%。
大剂量DZX介导的胰岛素抑制作用，联合适度热量限制和生活方式建议，与临床上显著的体重减轻相关。有必要进行更广泛的探索，以优化这种治疗方式并进一步阐明其风险和益处。
