Role of Hepatic Glycogen on Nocturnal Gluconeogenesis in Type 2 Diabetes Mellitus

Context: Higher gluconeogenesis (GNG) contributes to higher nocturnal endogenous glucose production (EGP) in type 2 diabetes (T2D). Studies using C-13 magnetic resonance spectroscopy (MRS) have confirmed lower hepatic glycogen content in subjects with T2D than in subjects with no diabetes (ND). Objective: We determined the role of glycogen loading (GL) vs nonglycogen loading (NGL) on the contribution of GNG to nocturnal EGP in T2D. Methods: In total, 14 subjects with T2D and 15 matched subjects with ND were studied on 2 occasions, with GL (60% carbohydrate) vs NGL (40% carbohydrate) isocaloric meals for 3 days, in random order in the overnight state. [6,6-H-2(2)] glucose was infused to measure EGP, deuterium labelled water was used to measure GNG, and C-13 MRS scans were performed in fed and fasted states to measure hepatic glycogen content. Results: Hepatic glycogen content and nocturnal EGP were higher (P < .05) in GL vs NGL in both cohorts. The % GNG to EGP averaged similar to 50% in subjects with ND throughout the night after both meals. In contrast, % GNG to nocturnal EGP in T2D was lower with GL vs NGL and matched the pattern observed in subjects with ND with GL lowering overnight rates of GNG in subjects with T2D. Conclusion: Selective targeting of GNG at night with appropriate medications could reduce nocturnal and early morning fasting hyperglycemia and hepatic insulin resistance in people with T2D.