Journal
CELL METABOLISM
Volume 31, Issue 4, Pages 699-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2020.02.013
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Funding
- University of Basel [DMS2427]
- Margot und Erich Goldschmidt & Peter Rene Jacobson-Stiftung
- alumni of the medical faculty of the University of Basel
- ETH Zurich
- German Academic Scholarship Foundation
- Swiss National Research Foundation
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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-1 beta 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.gov NCT03200782; 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(likelihood 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, pval(LRT) = 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-1 beta in postprandial hypoglycemia after gastric bypass surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.
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