Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β.
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, pvallikelihood ratio test (LRT) = 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, pvalLRT = 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.
['Hepprich|Matthias|M|', 'Wiedemann|Sophia J|SJ|', 'Schelker|Benjamin L|BL|', 'Trinh|Beckey|B|', 'Stärkle|Alessandra|A|', 'Geigges|Marco|M|', 'Löliger|Jordan|J|', 'Böni-Schnetzler|Marianne|M|', 'Rudofsky|Gottfried|G|', 'Donath|Marc Y|MY|']
D000328:Adult D001559:Benzhydryl Compounds D018592:Cross-Over Studies D004311:Double-Blind Method D005260:Female D015390:Gastric Bypass D005947:Glucose D005960:Glucosides D006801:Humans D007003:Hypoglycemia D053590:Interleukin 1 Receptor Antagonist Protein D053583:Interleukin-1beta D008297:Male D008875:Middle Aged D019518:Postprandial Period D000075082:Proof of Concept Study D000077203:Sodium-Glucose Transporter 2 Inhibitors
hypoglycemia insulin IL-1 IL-1Ra SGLT2 adipositas bariatric surgery inflammation late dumping metabolism