Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
J Clin Endocrinol Metab. 2019 Jul 1;104(7):2601-2613. doi: 10.1210/jc.2018-02165.
Roux-en-Y gastric bypass (RYGB) surgery effectively prevents or treats type 2 diabetes (T2D). Adipose tissue (AT) mechanisms may be of importance.
To assess the relationship between early changes in whole-body and AT metabolism in surgically treated patients with T2D.
A randomized single-center study.
Nineteen patients with T2D with body mass index 30 to 45 kg/m2.
Thirteen patients were assessed at baseline and 4 and 24 weeks after RYGB (preceded by a 4-week low-calorie diet) and compared with 6 control patients continuing standard medical treatment: oral glucose tolerance test, subcutaneous AT biopsies for gene expression, adipocyte size, glucose uptake, lipolysis, and insulin action.
At 4 and 24 weeks post-RYGB, all patients but one had stopped diabetes medication. Fasting glucose, HbA1c, and insulin levels decreased and the Matsuda index increased compared with baseline (P < 0.01 for all), indicating improved whole-body insulin sensitivity. Mean adipocyte size significantly reduced, more at 4 than at 24 weeks; at 4 weeks, glucose uptake per adipocyte was lowered, and isoproterenol-stimulated lipolysis tended to increase, whereas the fold insulin effects on glucose uptake and lipolysis were unchanged. Expression of genes involved in fatty acid oxidation, CPT1b and adiponectin, was increased at 4 weeks, whereas leptin and E2F1 (involved in cell proliferation) were reduced (P < 0.05 for all).
Glycemic control and in vivo insulin sensitivity improved 4 weeks after RYGB, but adipocyte insulin sensitivity did not change despite a marked reduction in adipocyte size. Thus, mechanisms for a rapid improvement of T2D after RYGB may occur mainly in other tissues than adipose.
Roux-en-Y 胃旁路（RYGB）手术可有效预防或治疗 2 型糖尿病（T2D）。脂肪组织（AT）机制可能很重要。
评估 T2D 患者手术后全身和 AT 代谢早期变化之间的关系。
一项随机单中心研究。
19 名 T2D 患者，体重指数为 30 至 45 kg/m2。
13 名患者在 RYGB 前（先进行 4 周低热量饮食）和 4 周和 24 周时进行评估，并与 6 名继续接受标准药物治疗的对照患者进行比较：口服葡萄糖耐量试验、皮下 AT 活检用于基因表达、脂肪细胞大小、葡萄糖摄取、脂肪分解和胰岛素作用。
在 RYGB 后 4 周和 24 周时，所有患者（除了 1 名患者）都停止了糖尿病药物治疗。与基线相比，空腹血糖、HbA1c 和胰岛素水平降低，Matsuda 指数升高（所有 P < 0.01），表明全身胰岛素敏感性提高。平均脂肪细胞大小显着减小，4 周时比 24 周时减小更多；4 周时，每个脂肪细胞的葡萄糖摄取减少，异丙肾上腺素刺激的脂肪分解趋于增加，而胰岛素对葡萄糖摄取和脂肪分解的作用倍数不变。参与脂肪酸氧化的基因 CPT1b 和脂联素的表达在 4 周时增加，而瘦素和 E2F1（参与细胞增殖）的表达减少（所有 P < 0.05）。
RYGB 后 4 周时血糖控制和体内胰岛素敏感性改善，但尽管脂肪细胞大小显着减小，脂肪细胞胰岛素敏感性并未改变。因此，RYGB 后 T2D 迅速改善的机制可能主要发生在脂肪以外的其他组织中。
