Schütt M, Brinkhoff J, Drenckhan M, Lehnert H, Sommer C
Department of Internal Medicine I, University of Lübeck, Lübeck, Germany.
Exp Clin Endocrinol Diabetes. 2010 Jul;118(7):449-52. doi: 10.1055/s-0030-1248289. Epub 2010 Mar 3.
Topiramate is an anticonvulsant agent effective in the prophylaxis of migraine, which also induces weight reduction by an unknown mechanism. We investigated the effect of topiramate on metabolic and endocrine parameters in patients with migraine independently of any intention to lose body weight. Six patients (26-61 years old, body mass indices [BMI] 20.9-32.1 kg/m(2)) with migraine were treated with an average dose of 100 mg topiramate/day over a period of 20 weeks. The following parameters were measured every 4-8 weeks: BMI, body fat proportion, waist and hip circumference, HOMA insulin resistance, fasting serum-/plasma concentrations of adiponectin, leptin, ghrelin, vascular endothelial growth factor (VEGF), cortisol, interleukin-6 and tumor necrosis factor (TNF)-alpha. Profound metabolic changes were observed for the whole treatment period. Compared with the baseline value, 20 weeks of treatment reduced the BMI by 7.2+/-1.4%, body fat proportion by 11.6+/-3.6%, waist circumference by 4.2+/-1.2%, leptin by 39.2+/-6.5% and HOMA insulin resistance by 37.3+/-5%, while adiponectin was increased by 69.9+/-17.3% (P<0.05, respectively). VEGF concentrations increased during the week 2-4 by 177.4+/-39.4% (P<0.05) followed by a continuous decrease. There were trends for a reduction in ghrelin concentration, whereas cortisol, interleukin-6 and TNF-alpha values were unchanged. In summary, in this small sample of migraine patients topiramate treatment was associated with increased insulin sensitivity, increased adiponectin concentration and a reduction of body fat in all treated patients. The role of increased VEGF concentrations prior to these metabolic changes is not clear and might, hypothetically, involve a centrally mediated effect of topiramate on body weight regulation.
托吡酯是一种有效的抗惊厥药物，可预防偏头痛，其还能通过未知机制减轻体重。我们研究了托吡酯对偏头痛患者代谢和内分泌参数的影响，而不考虑任何减轻体重的意图。6名偏头痛患者（年龄26 - 61岁，体重指数[BMI] 20.9 - 32.1 kg/m²）接受了为期20周的治疗，平均每日服用100 mg托吡酯。每4 - 8周测量以下参数：BMI、体脂比例、腰围和臀围、HOMA胰岛素抵抗、空腹血清/血浆脂联素、瘦素、胃饥饿素、血管内皮生长因子（VEGF）、皮质醇、白细胞介素-6和肿瘤坏死因子（TNF）-α。在整个治疗期间观察到了显著的代谢变化。与基线值相比，20周的治疗使BMI降低了7.2±1.4%，体脂比例降低了11.6±3.6%，腰围降低了4.2±1.2%，瘦素降低了39.2±6.5%，HOMA胰岛素抵抗降低了37.3±5%，而脂联素增加了69.9±17.3%（均P<0.05）。VEGF浓度在第2 - 4周增加了177.4±39.4%（P<0.05），随后持续下降。胃饥饿素浓度有降低趋势，而皮质醇、白细胞介素-6和TNF-α值无变化。总之，在这个小样本的偏头痛患者中，托吡酯治疗与所有治疗患者胰岛素敏感性增加、脂联素浓度增加和体脂减少有关。VEGF浓度在这些代谢变化之前升高的作用尚不清楚，推测可能涉及托吡酯对体重调节的中枢介导作用。
