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 ADA guidelines have sub-categorized '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 under-appreciated. 'Marked' hypoglycemia (~2.6mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of 'mild' hypoglycemia (3.0-3.9mmol/L) is unknown. Objective: To determine the effects of two levels of hypoglycemia, 2.6mmol/L ('marked') and 3.6mmol/L ('mild'), on gastric emptying in health. Design, Setting and Subjects: Fourteen healthy male participants (mean age: 32.9 ± 8.3 years, BMI: 24.5 ± 3.4 kg/m 2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100g beef) by scintigraphy over 120 min on 3 separate occasions, while blood glucose was maintained at either ~2.6mmol/L, ~3.6mmol/L, or ~6 mmol/L in random order from 15 min before until 60 min after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6mmol/L between 60-120 min on all days. Results: Gastric emptying was accelerated during both mild (P=0.011) and marked (P=0001) hypoglycemia when compared to euglycemia, and was more rapid during marked, when compared to 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.