Effect of Glucagon on Nocturnal Rates of Endogenous Glucose Production in Type 2 Diabetes

Abstract

The role of nocturnal glucagon on regulation of overnight endogenous glucose production (EGP) in T2D is unknown. We studied 13 T2D and 13 age, BMI matched nondiabetic subjects (ND) on two occasions at the Clinical Research Unit at Mayo Clinic. Deuterated water was provided to measure gluconeogenesis (GNG) and glycogenolysis (GGL) using the HMT (hexamethylenetetramine) method. A somatostatin pancreatic clamp was initiated at 10 PM with 0.25 mU/kg/min insulin infusion until 7 AM along with [3-3H] glucose to measure turnover in the presence of glucagon infusions at 0.65 ng/kg/min (basal) or 1.5 ng/kg/min (high) in random order. Blood was sampled periodically for the measurements of plasma glucose, [3-3H] glucose, hormones; EGP rates were measured at 7AM. Results are presented in the Table. Fasting glucose, insulin and c-peptide concentrations were not different in either group during either visit. Glucose infusion rates (GIR) required to maintain euglycemia were lower during high glucagon in both groups and lower in T2D vs. ND regardless of visit indicating insulin resistance. Rates of EGP at 7AM were higher in both groups with the high vs. basal glucagon (matched data shown for calculation). Partial GNG data that are available indicate increased rates of GGL at 7 AM in the presence of high glucagon. In T2D higher glucagon overnight could contribute to higher rates of GGL and EGP. Therapies to reduce GGL may help lower overnight EGP.{F280D615-E887-4E30-8C76-ED88282D5E23}All data are Mean +/- SD. Statistical analyses was not performed on EGP and HMT data as it is preliminary.Diabetes StatusBasal Glucagon 7 AMHigh Glucagon 7 AM7 AM p-value Basal vs HighGlucose (mmol/L)ND T2D5.4 ± 0.6 8.2 ± 4.0 (p < 0.001)5.2 ± 0.6 8.2 ± 4.0 (p < 0.001)0.4 0.9Glucagon (pg/ml)ND T2D82.0 ± 14.0 90.5 ± 12.5 (p = 0.56)138.3 ± 15.4 151.5 µ 17.2 (p = 0.20)p < 0.01 p < 0.01GIR (µmol/kgFFM/min)ND T2D23.0 ± 12.8 6.7 ± 8.4 (p <0.001)21.0 ± 11.4 4.0 ± 6.8 (p <0.001)p < 0.01 p < 0.01EGP (µmol/kgFFM/min)ND n=13 T2D n=138.0 ± 4.2 13.3 ± 4.710.3 ± 6.6 15.8 ± 4.3HMT data (EGP) (µmol/kgFFM/min)ND n=4 T2D n=710.3 ± 4.8 15.2 ± 5.615.1 ± 8.7 22.0 ± 5.0GluconeogenesisND n=4 T2D n=73.8 ± 1.3 5.6 ± 2.24.7 ± 3.4 9.4 ± 1.6GlycogenolysisND n=4 T2D n=76.5 ± 3.4 9.6 ± 3.310.4 ± 1.2 12.6 ± 3.5 Disclosure A. Basu: Research Support; Spouse/Partner; AstraZeneca. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Voluntis France. H. Zhai: None. R. Carter: None. R. Basu: Research Support; Self; AstraZeneca.