Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, and Department of Biomedicine, University of Basel, Basel, Switzerland; Endocrinology and Metabolic Diseases, Cantonal Hospital Olten, Olten, Switzerland.
Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, and Department of Biomedicine, University of Basel, Basel, Switzerland.
Cell Metab. 2020 Apr 7;31(4):699-709.e5. doi: 10.1016/j.cmet.2020.02.013. Epub 2020 Mar 19.
Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, crossover study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra (clinicaltrials.govNCT03200782; n = 12). Both drugs reduced postprandial insulin release and prevented hypoglycemia (symptomatic events requiring rescue glucose: placebo = 7/12, empagliflozin = 2/12, and anakinra = 2/12, pval = 0.013; nadir blood glucose for placebo = 2.4 mmol/L, 95% CI 2.18-2.62, empagliflozin = 2.69 mmol/L, 95% CI 2.31-3.08, and anakinra = 2.99 mmol/L, 95% CI 2.43-3.55, pval = 0.048). Moreover, analysis of monocytes ex vivo revealed a hyper-reactive inflammatory state that has features of an exaggerated response to a meal. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after gastric bypass surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.
胃旁路手术后发生的餐后低血糖是肥胖治疗的一种致残性并发症。目前尚无治疗方法，其潜在机制仍不清楚。在这里，我们假设葡萄糖诱导的 IL-1β 导致这种情况下胰岛素反应过度。因此，我们进行了一项安慰剂对照、随机、双盲、交叉研究，使用 SGLT2 抑制剂恩格列净和 IL-1 受体拮抗剂阿那白滞素（clinicaltrials.govNCT03200782；n=12）。两种药物均降低了餐后胰岛素释放并预防了低血糖（需要抢救葡萄糖的症状性事件：安慰剂=7/12，恩格列净=2/12，阿那白滞素=2/12，pval=0.013；安慰剂的血糖最低点为 2.4mmol/L，95%CI 2.18-2.62，恩格列净=2.69mmol/L，95%CI 2.31-3.08，阿那白滞素=2.99mmol/L，95%CI 2.43-3.55，pval=0.048）。此外，对体外单核细胞的分析显示出一种过度活跃的炎症状态，具有对餐食反应过度的特征。我们的研究提出了胃旁路手术后餐后低血糖与葡萄糖诱导的 IL-1β 之间的关系，并表明 SGLT2 抑制剂和 IL-1 拮抗作用可能改善这种情况。
