First-Phase Insulin Secretion Has Limited Impact on Postprandial Glycemia in Subjects with Type 2 Diabetes: Correlations Between Hyperglycemic Glucose Clamp and Meal Test

Abstract

Background:

Lack of first-phase insulin (INS) secretion is regarded as causative for high postprandial glucose excursions in subjects with type 2 diabetes. We aimed to determine the impact of early INS secretion on postprandial glycemia.

Methods:

Twenty subjects with type 2 diabetes (age 54 ± 8 years, body mass index 28.7 ± 2.7 kg/m² [mean ± SD]) underwent a hyperglycemic glucose clamp and a meal test twice separated by a washout period of 4 weeks. Multiple regression analysis was used to identify determinants of postprandial glycemia.

Results:

During hyperglycemic glucose clamps eight subjects showed a preserved first-phase INS secretion (P1+), whereas 12 subjects showed none (P1−). Both subject groups differed in fasting blood glucose (BG) (116 ± 7 vs. 147 ± 31 mg/dL, P = 0.011) and glycosylated hemoglobin (6.0 ± 0.4 vs. 6.7 ± 0.8, P = 0.041). Total INS secretory response during glucose clamps was higher in P1+ than P1− (INS-area under the concentration vs. time curve [AUC]_{0–120 min} 6.7 ± 2.7 vs. 3.2 ± 2.1 mU·min/mL; P = 0.006). During meal tests, however, INS-AUC_{0–120 min} was similar between P1+ and P1−, whereas early INS secretion was still different (INS-AUC_0–60 min 3.9 ± 1.8 vs. 2.1 ± 1.0 mU·min/mL; P = 0.031). Despite higher INS-AUC_0–60 min in P1+, early postprandial BG was comparable between groups (BG-AUC_0–60 min 1.5 ± 0.5 vs. 1.6 ± 0.6 g·min/dL; difference not significant). Multiple regression analyses showed no impact of first-phase INS secretion on postprandial glycemia, either in P1+ or in P1−. Nevertheless, in P1−, but not in P1+, postprandial glycemia was negatively correlated with INS sensitivity (R ² = 0.83, P < 0.001).

Conclusions:

This study, correlating results of hyperglycemic glucose clamps with meal tests, shows that a preserved first-phase INS secretion has only a limited impact on postprandial glucose excursions in a group of subjects in early-stage type 2 diabetes.