We have read the study by Kramer et al. (1) concerning glucagon response to oral glucose challenge in type 1 diabetes with great interest. Although a paradoxical increase in glucagon in response to oral glucose may be one of the significant causes of hyperglycemia in patients with type 1 diabetes, its results should be carefully interpreted from various perspectives. First, this study demonstrated neither the insulin infusion rate for each participant to control blood glucose levels before oral glucose challenge nor the basal insulin infusion rate of continuous subcutaneous insulin at usual clinical settings during glucose challenge. Previous studies suggested that glucagon levels were lower in participants receiving high-dose insulin than in those with low-dose insulin (2). Their blood insulin levels, which may influence glucagon levels, should be considered for glucagon response. Second, it was unclear whether hypoglycemic events occurred before this study began. Some studies revealed that hypoglycemic events influenced the secretion of counterregulatory hormones such as glucagon and catecholamines (3); therefore, information on hypoglycemia is essential for this study. Finally, blood glucagon is supplied by not only pancreatic but also extrapancreatic sources. Vranic et al. (4) found that glucagon levels in pancreatomized dogs increased significantly after the cessation of their insulin therapy; this was as a result of “extrapancreatic glucagon” secretions. After this discovery, some studies reported on the insulin, arginine, and somatostatin effect on the secretion of extrapancreatic glucagon (5). Further research is required to clarify the relationship between glucagon response and glucose levels in consideration of the many variables, including insulin levels, hypoglycemic episodes, and the secretion of pancreatic and extrapancreatic glucagon.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.