Plasma glucagon levels measured by sandwich ELISA are correlated with impaired glucose tolerance in type 2 diabetes

Glucagon dysfunction as well as insulin dysfunction is associated with the pathogenesis of type 2 diabetes (T2DM). However, it is still unclear whether the measurement of plasma glucagon levels is useful in understanding the pathophysiology of T2DM. We recently reported that sandwich ELISA provides more accurate plasma glucagon values than conventional RIA in healthy subjects. Here we used sandwich ELISA as well as RIA to assess plasma glucagon levels, comparing them in T2DM patients and healthy subjects during oral glucose (OGTT) or meal tolerance tests (MTT). We confirmed that sandwich ELISA was able to detect more significant difference between healthy subjects and T2DM patients in the fasting levels and the response dynamics of plasma glucagon than RIA. We also found significant differences in the following glucagon parameters: (1) fasting glucagon, (2) the area under the curve (AUC) of glucagon in OGTT, and (3) the change in glucagon between 0 and 30 min (Delta Glucagon(0-0.5h)) in OGTT or MTT. Among these, the most apparent difference was Delta Glucagon(0-0.5h) in MTT. When we divided T2DM patients into two groups whose Delta Glucagon(0-0.5h) in MTT was either below or above the maximum value in healthy subjects, the group with higher Delta Glucagon(0-0.5h) showed more significant impairment of glucose tolerance. These results suggest that the assessment of plasma glucagon levels by sandwich ELISA might enhance our understanding of the pathophysiology of T2DM.