Brunani A, Caumo A, Graci S, Castagna G, Viberti G, Liuzzi A
Department of Internal Medicine, Ospedale San Giuseppe, IRCCS, Istituto Auxologico Italiano, Verbania, Italy.
Diabetes Obes Metab. 2008 Jun;10(6):460-7. doi: 10.1111/j.1463-1326.2007.00728.x. Epub 2007 Mar 29.
In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone.
From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18-65 years and body mass index 35-50 kg/m(2) and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism.
A significant weight loss and reduction of fat mass was demonstrated with metformin (-9.7 +/- 1.8 kg and -6.6 +/- 1.1 kg) and also with rosiglitazone (-11.0 +/- 1.9 kg and -7.2 +/- 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 +/- 1.5 vs. 8.0 +/- 0.,7 microU/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 +/- 8.8 vs. 109.9 +/- 10.3, p < 0.005) with a concomitant decrease in beta-cell function as measured by HOMA of beta-cell function (163.2 +/- 16.1 vs. 127.4 +/- 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments.
Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction.
在肥胖患者中，饮食诱导的体重减轻可显著改善糖耐量，增加胰岛素敏感性并部分降低胰岛素分泌。与二甲双胍治疗联合使用可能会增强单纯饮食的效果。
从我院营养科接受饮食计划的患者中，选取年龄在18 - 65岁、体重指数为35 - 50kg/m²的肥胖、非糖尿病且无并发症的患者，研究二甲双胍（850mg，每日两次）或罗格列酮（4mg，每日两次）进行6个月药物治疗对体重、脂肪量、糖脂代谢可能产生的变化。
二甲双胍组（体重减轻-9.7±1.8kg，脂肪量减少-6.6±1.1kg）和罗格列酮组（体重减轻-11.0±1.9kg，脂肪量减少-7.2±1.8kg）均出现显著的体重减轻和脂肪量减少，且两组均无液体潴留。罗格列酮治疗使血糖浓度显著降低（4.7±0.1 vs. 4.4±0.1mmol/L, p < 0.005）和胰岛素循环水平显著降低（13.6±1.5 vs. 8.0±0.7μU/ml, p < 0.005），通过胰岛素敏感性稳态模型评估（HOMA）测得胰岛素敏感性增加（从68.9±8.8增至109.9±10.3, p < 0.005），同时通过β细胞功能HOMA测得β细胞功能降低（从163.2±16.1降至127.4±8.4, p < 0.005）。相比之下，二甲双胍对血糖浓度、胰岛素水平和HOMA2指数无显著影响。药物治疗未记录到不良事件。
我们的研究表明，在接受营养计划的严重肥胖、非糖尿病、高胰岛素血症患者中，罗格列酮在改善基于空腹的糖代谢指标方面比二甲双胍更有效，可同时降低胰岛素抵抗和高胰岛素血症。尽管之前的研究报道罗格列酮会导致体重增加，但在我们的研究中，饮食与罗格列酮联合治疗伴随着体重减轻和脂肪量减少。
