Acceleration of Gastric Emptying by Insulin-Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia

Abstract

Context: Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized "non-severe"hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. "Marked"hypoglycemia (2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of "mild"hypoglycemia (3.0-3.9 mmol/L) is unknown. Objective: To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L ("marked") and 3.6 mmol/L ("mild"), on gastric emptying in health. Design, Setting, and Subjects: Fourteen healthy male participants (mean age: 32.9±8.3 years; body mass index: 24.5±3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either 2.6 mmol/L, 3.6 mmol/L, or 6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. Results: Gastric emptying was accelerated during both mild (P=0.011) and marked (P=0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P=0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r=0.57, P=0.030) and marked (r=0.76, P=0.0014) hypoglycemia was related to gastric emptying during euglycemia. Conclusion: In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.