Hepatic Glycogen Metabolism in Type 1 Diabetes After Long-Term Near Normoglycemia

Abstract

We tested the impact of long-term near normoglycemia (HbA_1c <7% for >1 year) on glycogen metabolism in seven type 1 diabetic and seven matched nondiabetic subjects after a mixed meal. Glycemic profiles (6.2 ± 0.10 vs. 5.9 ± 0.07 mmol/l; P < 0.05) of diabetic patients were approximated to that of nondiabetic subjects by variable insulin infusion. Rates of hepatic glycogen synthesis and breakdown were calculated from the glycogen concentration time curves between 7:30 p.m. and 8:00 a.m. using in vivo ¹³C nuclear magnetic resonance spectroscopy. Glucose production was determined with d-[6,6-²H₂]glucose, and the hepatic uridine-diphosphate glucose pool was sampled with acetaminophen. Glycogen synthesis and breakdown as well as glucose production were identical in diabetic and healthy subjects: 7.3 ± 0.9 vs. 7.1 ± 0.7, 4.2 ± 0.5 vs. 3.8 ± 0.3, and 8.7 ± 0.5 vs. 8.4 ± 0.7 μmol · kg⁻¹ · min⁻¹, respectively. Although portal vein insulin concentrations were doubled, the flux through the indirect pathway of glycogen synthesis remained higher in type 1 diabetic subjects: ∼70 vs. ∼50%; P < 0.05. In conclusion, combined long- and short-term intensified insulin substitution normalizes rates of hepatic glycogen synthesis but not the contribution of gluconeogenesis to glycogen synthesis in type 1 diabetes.