Increased postprandial GIP and glucagon responses, but unaltered GLP-1 response after intervention with steroid hormone, relative physical inactivity, and high-calorie diet in healthy subjects

Abstract

Objective: Increased postprandial glucose-dependent insulinotropic polypeptide (GIP) and glucagon responses and reduced postprandial glucagon-like peptide-1 (GLP-1) responses have been observed in some patients with type 2 diabetes mellitus. The causality of these pathophysiological traits is unknown. We aimed to determine the impact of insulin resistance and reduced glucose tolerance on postprandial GIP, GLP-1, and glucagon responses in healthy subjects. Research Design and Methods: A 4-h 2200 KJ-liquid meal test was performed in 10 healthy Caucasian males without family history of diabetes [age, 24 ± 3 yr (mean ± SD); body mass index, 24 ± 2 kg/m 2; fasting plasma glucose, 4.9 ± 0.3 mM; hemoglobin A 1c, 5.4 ± 0.1%] before and after intervention using high-calorie diet, relative physical inactivity, and administration of prednisolone (37.5 mg/d) for 12 d. Results: The intervention resulted in insulin resistance according to the homeostatic model assessment [1.1±0.3 vs. 2.3 (mean±SEM)±1.3; P=0.02] and increased postprandial glucose excursions [area under curve (AUC), 51 ± 28 vs. 161 ± 32 mM·4 h; P = 0.045], fasting plasma insulin (36 ± 3 vs. 61 ± 6 pM; P = 0.02), and postprandial insulin responses (AUC, 22 ± 6 vs. 43 ± 13 nM·4 h; P = 0.03). This disruption of glucose homeostasis had no impact on postprandial GLP-1 responses (AUC, 1.5 ± 0.7 vs. 2.0 ± 0.5 nM·4 h; P = 0.56), but resulted in exaggerated postprandial GIP (6.2 ± 1.0 vs. 10.0 ± 1.3 nM·4 h; P = 0.003) and glucagon responses (1.6 ± 1.5 vs. 2.4 ± 3.2; P = 0.007). Conclusions: These data suggest that increased postprandial GIP and glucagon responses may occur as a consequence of insulin resistance and/or reduced glucose tolerance. Our data suggest that acute disruption of glucose homeostasis does not result in reduced postprandial GLP-1 responses as observed in some individuals with type 2 diabetes mellitus. Copyright © 2011 by The Endocrine Society.