Higher gluconeogenesis (GNG) during the latter part of the night contributes to higher endogenous glucose production (EGP) in type 2 diabetes (T2D). We have shown that glycogen synthesis is reduced in T2D due to a functional defect in the rate-limiting hepatic glucokinase activity. Studies using MRIs have confirmed lower net hepatic glycogen content in T2D than subjects without diabetes (ND) before and after dinner. We hypothesize that increasing post dinner hepatic glycogen content might restore overnight EGP in T2D by reducing GNG. 14 T2D and 15 anthropometrically matched ND were randomly assigned to glycogen loading (GL; 60% carb) vs. non glycogen loading (NGL; 40% carb) meals for 3 days. [6,6-2H2] Glucose was infused to measure EGP. GNG was estimated with deuterium labeled water and glycogen content measured via C13 NMR in fed and fasted state. Results are shown in Figure1. Liver glycogen content was higher with GL vs NGL in both cohorts. EGP was higher (p<0.05) in GL vs NGL throughout night in both cohorts. The percent contribution of GNG and glycogenolysis (GGL) to EGP averaged ~ 50% in ND throughout the night in both GL and NGL. In contrast, the percent contribution of GNG to EGP in T2D with GL was lower vs. NGL overnight (average ~48% vs. 60%) and matched the pattern observed in ND with GL. The results indicate that lower glycogen content in the liver contributes to increased nocturnal rates of GNG in T2D.
U.Unni: None. Y.Yadav: None. J.P.Mugler, iii: None. R.Carter: None. A.Basu: None. R.Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca.
National Institute for Health and Care Research (R01DK029953)
