Hepatic glycogen metabolism in type 1 diabetes after long-term near normoglycemia.
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 (13)C nuclear magnetic resonance spectroscopy. Glucose production was determined with D-[6,6-(2)H(2)]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 micromol x kg(-1) x 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: approximately 70 vs. approximately 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.
Bischof
Martin G
MG
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Vienna, Austria.
Bernroider
Elisabeth
E
Krssak
Martin
M
Krebs
Michael
M
Stingl
Harald
H
Nowotny
Peter
P
Yu
Chunlin
C
Shulman
Gerald I
GI
Waldhäusl
Werner
W
Roden
Michael
M
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005943:Gluconeogenesis; D006442:Glycated Hemoglobin / Q000032:analysis; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007700:Kinetics; D008112:Liver Glycogen / Q000096:biosynthesis / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D012016:Reference Values; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D006854:Hydrocortisone; D007004:Hypoglycemic Agents; D007328:Insulin; D008112:Liver Glycogen; D014532:Uridine Diphosphate Glucose