Continuous glucose monitoring reveals glycemic variability and hypoglycemia after vertical sleeve gastrectomy in rats

Abstract Objective Post-bariatric surgery hypoglycemia (PBH) is defined as the presence of neuroglycopenic symptoms accompanied by postprandial hypoglycemia in bariatric surgery patients. Recent clinical studies using continuous glucose monitoring (CGM) technology revealed that PBH is more frequently observed in vertical sleeve gastrectomy (VSG) patients than previously recognized. PBH cannot be alleviated by current medication. Therefore, a model system to investigate the mechanism and treatment is required. Methods We utilized CGM in a rat model of VSG and monitored the occurrence of glycemic variability and hypoglycemia in various meal conditions for 4-weeks after surgery. Another cohort of rat VSG with CGM was utilized to investigate whether the blockade of glucagon-like peptide-1 receptor (GLP-1R) signaling alleviates these symptoms. A mouse VSG model was utilized to investigate whether the impaired glucose counterregulatory system causes postprandial hypoglycemia. Results Like in humans, rats have increased glycemic variability and hypoglycemia after VSG. Postprandial hypoglycemia specifically detected after liquid vs. solid meals. Further, the blockade of GLP-1R signaling raises the glucose nadir but does not affect glycemic variability. Conclusions Rat bariatric surgery duplicates many features of human post bariatric surgery hypoglycemia including postprandial hypoglycemia and glycemic variability, while blockade of GLP-1 receptor signaling prevents the hypoglycemia but the variability.