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

Abstract

Aims/introduction: To evaluate the contribution of pancreatic α-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_{glc RIA} ) and enzyme-linked immunosorbent assays (AUC_{glc ELISA} ). 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_{glc RIA} (R² = 0.03, P = 0.39) or AUC_{glc ELISA} (R² = 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_{glc RIA} (R² = 0.20, P = 0.02) and AUC_{glc ELISA} (R² = 0.21, P = 0.02). The median hepatic glucose uptake (65.3%, interquartile range 40.0-87.3%) was not correlated with AUC_{glc RIA} (R² = 0.07, P = 0.26) or AUC_{glc ELISA} (R² = 0.26, P = 0.79). The standard deviation of glucose levels measured by continuous glucose monitoring was significantly correlated with AUC_{glc RIA} (R² = 0.11, P = 0.049), but not with AUC_{glc ELISA} (R² = 0.01, P = 0.75).

Conclusions: Pancreatic α-cell function contributed to insulin sensitivity in patients with type 1 diabetes.

Keywords: Insulin sensitivity; Pancreatic α-cell; Type 1 diabetes.