Hypoglycemia after Bariatric Surgery in Mice and Optimal Dosage and Efficacy of Glucose Supplementation

• Published in: Comparative medicine Vol. 70; no. 2; pp. 111 - 118
• Main Authors: Hsi, Zoe Y, Stewart, Leslie A, Lloyd, KC Kent, Grimsrud, Kristin N
• Format: Journal Article
• Language: English
• Published: United States American Association for Laboratory Animal Science 01-04-2020
• Subjects: Animals; Disease Models, Animal; Female; Gastric Bypass - adverse effects; Gastric Bypass - mortality; Glucose - administration & dosage; Glucose - pharmacokinetics; Hypoglycemia - drug therapy; Hypoglycemia - etiology; Injections, Subcutaneous; Male; Mice; Mice, Inbred C57BL; Original Research
• ISSN: 1532-0820; 2769-819X
• DOI: 10.30802/AALAS-CM-19-000015

The Roux-en-Y Gastric Bypass (RYGB) mouse model is a vital tool for studying the pathophysiology of bariatric surgery and contributes greatly to research on obesity and diabetes. However, complications including postsurgical hypoglycemia can have profoundly negative effects. Unlike
in humans, blood glucose (BG) is not typically managed in postoperative rodents, despite their critical role as translational models; without this management, rodents can experience hypoglycemia, potentially impairing wound healing, decreasing survivability, complicating interpretation of
research data, and limiting translational utility. In this project, we sought to identify an optimal method for minimally invasive administration of dextrose in C57BL/6N (n = 16; 8 male, 8 female) mice. To do so, we characterized BG pharmacokinetic profiles after subcutaneous and oral-transmucosal
(OTM) administration of dextrose. Compared with OTM dosage, the subcutaneous route provided more consistent and reliable delivery of glucose and did not cause significant adverse reactions. We then evaluated the frequency of hypoglycemic events after RYGB in C57BL/6N mice (n = 16; 8
male, 8 female) and the effects of subcutaneous dextrose supplementation on morbidity and mortality. BG measurement and behavioral pain assessment (grimace test) were performed for 3 d after surgery. Hypoglycemic (BG ≤ 60 mg/dL) animals were assigned to dose (5% dextrose SC) or no-dose
treatment groups. Nearly all (87%) mice became hypoglycemic; 2 of these mice died. No significant intergroup difference in grimace score or mortality was detected. Overall, our results demonstrate that hypoglycemia is a frequent adverse event after RYGB in mice and that subcutaneous injection
of dextrose is a safe and effective way to manage hypoglycemia. Further studies are necessary to optimize the intervention threshold and optimal dosage; regardless, we recommend glycemic management after RYGB surgery in mice.