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

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 A1c, 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. (J Clin Endocrinol Metab 96: 447-453, 2011)