Contribution of pancreatic α-cell function to insulin sensitivity and glycemic variability in patients with type 1 diabetes

Aims/Introduction To evaluate the contribution of pancreatic alpha-cell function to the dawn phenomenon, insulin sensitivity, hepatic glucose uptake and glycemic variability in patients with type 1 diabetes. Materials and Methods In 40 patients with type 1 diabetes, arginine stimulation tests were carried out, and the area under the curve (AUC) of glucagon was measured using radioimmunoassays (AUC(glcRIA)) and enzyme-linked immunosorbent assays (AUC(glcELISA)). The ratio of the insulin dose delivered by an artificial pancreas to maintain euglycemia between 04.00 and 08.00 hours or between 00.00 and 04.00 hours was measured as the dawn index. The glucose infusion rate and hepatic glucose uptake were measured using hyperinsulinemic euglycemic clamp and clamp oral glucose loading tests. Glycemic variability in 96 h was measured by continuous glucose monitoring. Results The median dawn index (1.7, interquartile range 1.0-2.8) was not correlated with AUC(glcRIA) (R-2 = 0.03, P = 0.39) or AUC(glcELISA) (R-2 = 0.04, P = 0.32). The median glucose infusion rate (7.3 mg/kg/min, interquartile range 6.4-9.2 mg/kg/min) was significantly correlated with AUC(glcRIA) (R-2 = 0.20, P = 0.02) and AUC(glcELISA) (R-2 = 0.21, P = 0.02). The median hepatic glucose uptake (65.3%, interquartile range 40.0-87.3%) was not correlated with AUC(glcRIA) (R-2 = 0.07, P = 0.26) or AUC(glcELISA) (R-2 = 0.26, P = 0.79). The standard deviation of glucose levels measured by continuous glucose monitoring was significantly correlated with AUC(glcRIA) (R-2 = 0.11, P = 0.049), but not with AUC(glcELISA) (R-2 = 0.01, P = 0.75). Conclusions Pancreatic alpha-cell function contributed to insulin sensitivity in patients with type 1 diabetes.