Abstract
BackgroundGlucagon stimulation test (GST) is often employed to assess the insulin reserve of the pancreatic beta cells in diabetic subjects. The clinical significance of the increment of plasma glucose (Δglucose) by exogenous glucagon during GST has not been elucidated. We investigated the relationship between Δglucose and clinical parameters including the liver and renal function in type 2 diabetic subjects, since we hypothesized that Δglucose is associated with the liver and renal function reflecting the capacity for gluconeogenesis in the organs.MethodsA total of 209 subjects with type 2 diabetes who underwent GST during admission were included in this cross-sectional study. We defined the difference between plasma glucose at fasting and 6 min after intravenous injection of 1 mg glucagon as Δglucose. We assessed correlations between Δglucose and clinical parameters such as diabetic duration, BMI, HbA1c, beta cell function, serum free fatty acids (FFA) which is known to stimulate gluconeogenesis, liver function, the indices of liver function, renal function, and urinary albumin excretion (UAE).ResultsIn correlation analysis, Δglucose positively correlated to FFA and estimated glomerular filtration rate (eGFR), but inversely to serum creatinine and cystatin C, although Δglucose showed no correlation with both liver function and the indices of residual liver function. Multiple regression analysis revealed that Δglucose was an independent determinant for the eGFR after 1 year, equally BMI, HbA1c, serum lipids, and UAE, which are known as the predictors for the development of chronic kidney disease.ConclusionOur results suggest that Δglucose during GST might be related to gluconeogenesis in the kidney and could be the determinant of future renal function in type 2 diabetes.
Highlights
Glucagon stimulation test (GST) is often employed to assess the insulin reserve of the pancreatic beta cells in diabetic subjects
The increment of plasma glucose levels (Δglucose) by exogenous glucagon during GST is presumed to reflect a part of glucose output from the liver that might be attributed to gluconeogenesis and glycogenolysis, the clinical significance of Δglucose has not been elucidated
We investigated the relationship in subjects with type 2 diabetes mellitus (T2DM) between Δglucose and clinical parameters such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as liver function, serum creatinine, cystatin C and estimated glomerular filtration rate as renal function, serum free fatty acids (FFA) which is known to stimulate gluconeogenesis, and albumin, cholinesterase (ChE), bilirubin, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and prothrombin time (PT) employed as the indices reflecting residual liver function
Summary
Glucagon stimulation test (GST) is often employed to assess the insulin reserve of the pancreatic beta cells in diabetic subjects. The clinical significance of the increment of plasma glucose (Δglucose) by exogenous glucagon during GST has not been elucidated. Glucagon stimulation test (GST) has been often used to assess the insulin reserve of the pancreatic beta cells in subjects with diabetes by measuring plasma C-peptide immunoreactivity (CPR) levels before and 6 min after exogenous intravenous glucagon injection [2, 3]. The increment of plasma glucose levels (Δglucose) by exogenous glucagon during GST is presumed to reflect a part of glucose output from the liver that might be attributed to gluconeogenesis and glycogenolysis, the clinical significance of Δglucose has not been elucidated. The kidney provides almost equal amounts of glucose to the liver into the circulation in the postabsorptive state [4]
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