Abstract

OBJECTIVE– Inappropriate excessive secretion of glucagon, which contributes to postprandial hyperglycemia, is a novel target for the treatment of diabetes. In this study, we sought to determine the factors associated with exaggerated glucagon secretion in response to an arginine challenge in patients with type 1 and type 2 diabetes.

RESEARCH DESIGN AND METHODS– Changes in circulating C-peptide immunoreactivity (CPR) and immunoreactive glucagon (IRG) after an arginine challenge were investigated in 35 patients with type 1 diabetes, 130 patients with type 2 diabetes, and 35 non-diabetic control subjects.

RESULTS– No significant differences were found in the basal level and the area under the concentration–time curve (AUC) of IRG (AUC_IRG) among type 1 and type 2 diabetic patients and non-diabetic subjects. However, the correlation between the AUC_IRG and the AUC of CPR (AUC_CPR) was inverse between type 1 (r = –0.388, P = 0.023) and type 2 diabetic patients (r = 0.396, P < 0.0001), whereas AUC_IRG was not correlated with AUC_CPR in non-diabetic subjects (r = -0.079, P = 0.655). In type 1 diabetic patients, the AUC_CPR decreased and the AUC_IRG increased with increasing disease duration. In type 2 diabetic patients, both AUC_IRG and AUC_CPR increased with increasing BMI, basal CPR level, and homeostatic model assessment of insulin resistance (HOMA-IR) value.

CONCLUSIONS– Our findings suggest that the pathophysiology of the exaggerated glucagon response differs between the types of diabetes. Intra-islet insulin deficiency and alpha cell insulin resistance may be the primary contributors to this condition in type 1 and type 2 diabetes, respectively.