The 'early' postprandial glucagon response to a mixed meal is dependent on the rate of gastric emptying in type 2 diabetes

Abstract

Background and aims: Gastric emptying (GE), which exhibits a substantial inter-individual variation, is a major determinant of postprandial glycaemic and insulinaemic responses in both health and type 2 diabetes (T2D). T2D is characterised by attenuated suppression of plasma glucagon after meals, which contributes to postprandial hyperglycaemia. The relationship between the postprandial glucagon response and GE has not been reported. We examined the relationship between plasma glucagon and GE of a standardised mixed meal in well-controlled T2D. Materials and methods: 94 patients with T2D managed by diet and/or metformin monotherapy (61 male, age 64.6 ± 0.7 years, BMI 29.8 ± 0.5 kg/m2 , HbA1c 6.6 ± 0.1% and duration of known diabetes 5.3 ± 0.5 years) were evaluated on a single study day. After an overnight fast, participants consumed a mashed potato meal (1541.8 kJ: 61.4g carbohydrate, 7.4g protein and 8.9g fat, labelled with 100 μL 13C-octanoic acid) between 0-5 min. Venous blood was sampled at t = 0, 15, 30, 60, 90, 120, 180, 240 min for measurements of blood glucose (glucometer) and plasma glucagon (radioimmunoassay). Gastric emptying was assessed by breath test. Data are mean values ± SEM. P < 0.05 was considered statistically significant. Results: After the meal, blood glucose concentrations increased progressively from 8.2 ± 0.1 mmol/L to the peak of 14.0 ± 0.31 mmol/L at t = 90 min, followed by a decline towards baseline. Plasma glucagon increased from a fasting level of 76.1 ± 2.1 pg/ml to a peak of 92.7 ± 2.6 pg/ml at t = 30 min and then decreased to a nadir of 65.6 ± 1.9 pg/ml at t = 180 min. The gastric half-emptying time (T50) was 68.2 ± 1.4 min (range 39-116 min). The incremental area under the plasma glucagon curve between t = 0-30min (glucagon iAUC0-30min) was inversely related to the T50 (r = - 0.3, P = 0.007). The magnitude of increases in blood glucose from baseline at t = 30 (r = -0.3, P = 0.0003), 60 (r = -0.5, P < 0.0001) and 90 min (r = -0.3, P = 0.004) were related inversely to the T50. The increase in blood glucose at t = 30 min was related directly to the glucagon iAUC0-30min (r = 0.3, P = 0.008). Conclusion: In well-controlled T2D, the early postprandial glucagon response to a mixed meal is related to the rate of gastric emptying, and predictive of the initial glycaemic response. These observations support the concept of slowing of gastric emptying to minimise postprandial glycaemic excursions in T2D.