Prandial hepatic glucose production during hypoglycemia is altered after gastric bypass surgery and sleeve gastrectomy

Marzieh Salehi, Amalia Gastaldelli, Ralph DeFronzo

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis: Roux-en Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) alter prandial glucose metabolism, producing lower nadir glucose values and predisposing susceptible individuals to prandial hypoglycemia. The glycemic phenotype of GB or SG is associated with prandial hyperinsulinemia and hyperglucagonemia along with an increased influx of ingested glucose. Following insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production (HGP). It is unclear whether prandial hyperglucagonemia after GB or SG changes HGP under hyperinsulinemic hypoglycemia conditions. This study examined the hypothesis that prandial glucose production is reduced after GB and SG during hypoglycemia. Methods: Glucose kinetics and islet-cell and gut hormone secretion during hyperinsulinemic (120 mU.m−2.min−1) hypoglycemic clamp (~3.2 mM) were measured before and after mixed meal ingestion in 9 non-diabetic subjects with GB, 7 with SG, and 5 matched non-operated controls (CN). Results: Systemic appearance of ingested glucose was faster in GB compared to SG, and in SG compared to CN (p < 0.05). Subjects with GB and SG had greater plasma glucagon levels after eating (AUCGlucagon) compared to CN (p < 0.05). But prandial HGP response during insulin-induced hypoglycemia (AUCHGP) was smaller and shorter in duration in surgical groups (p < 0.05). In the absence of meal stimuli, however, glucose counterregulatory response to hypoglycemia was comparable among the 3 groups during hyperinsulinemic clamp. Conclusion: After bariatric surgery, prandial glucose counterregulatory response to hypoglycemia is impaired. Considering post-meal hyperglucagonemia after GB or SG the blunted HGP response suggests a lower sensitivity of liver to glucagon that can predispose to hypoglycemia in this population.

Original languageEnglish (US)
Article number155199
JournalMetabolism: Clinical and Experimental
Volume131
DOIs
StatePublished - Jun 2022
Externally publishedYes

Keywords

  • Gastric bypass
  • Hepatic glucose production
  • Hypoglycemia
  • Livers sensitivity to glucagon
  • Sleeve gastrectomy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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