The 'early' postprandial glucagon response is related to the rate of gastric emptying in type 2 diabetes

Gastric emptying (GE) is a major determinant of the postprandial glycemic and insulinemic responses in health and type 2 diabetes (T2D). However, the effect of GE on the postprandial glucagon response, which is characteristically augmented in T2D, is unknown. This study examined the relationship between plasma glucagon and GE of a standardized mixed meal in individuals with well-controlled T2D. 89 individuals with T2D (HbA1c 6.6 ± 0.1%) consumed a mashed potato meal labeled with 100 µL ¹³C-octanoic acid between 0 and 5 min. Venous blood was sampled frequently over 4 h for measurements of blood glucose and plasma glucagon. The gastric half-emptying time (T50) was calculated by quantification of ¹³C in the breath. Blood glucose peaked at t = 90 min after the meal. Plasma glucagon increased to a peak at t = 30 min and then decreased to a nadir at t = 180 min. The T50 was 68.3 ± 1.6 min. The incremental area under the plasma glucagon curve between t = 0-30 min (glucagon iAUC_{0-30 min}) was related inversely to the T50 (r = -0.23, P = 0.029), while the increase in blood glucose at t = 30 min was related directly to the plasma glucagon iAUC_{0-30 min} (r = 0.25, P = 0.018). Accordingly, individuals with relatively faster GE exhibited higher postprandial glucagon and glucose levels (ANOVA: P<0.01 for each). In well-controlled T2D, the early postprandial glucagon response to a mixed meal is related to the rate of GE, and predictive of the initial glycemic response. These observations suggest that a reduction in plasma glucagon may contribute to the effect of dietary and pharmacological strategies which reduce postprandial glycemia in T2D by slowing GE.