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Diabetes 50:392-398, 2001
© 2001 by the American Diabetes Association, Inc.

Effects of Short-Term Improvement of Insulin Treatment and Glycemia on Hepatic Glycogen Metabolism in Type 1 Diabetes

Martin G. Bischof, Martin Krssak, Michael Krebs, Elisabeth Bernroider, Harald Stingl, Werner Waldhäusl, and Michael Roden

From the Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Vienna, Austria.

Address correspondence and reprint requests to Michael Roden, MD, Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: michael.roden{at}akh-wien.ac.at .

Insufficiently treated type 1 diabetic patients exhibit inappropriate postprandial hyperglycemia and reduction in liver glycogen stores. To examine the effect of acute improvement of metabolic control on hepatic glycogen metabolism, lean young type 1 diabetic (HbA1c 8.8 ± 0.3%) and matched nondiabetic subjects (HbA1c 5.4 ± 0.1%) were studied during the course of a day with three isocaloric mixed meals. Hepatic glycogen concentrations were determined noninvasively using in vivo 13C nuclear magnetic resonance spectroscopy. Rates of net glycogen synthesis and breakdown were calculated from linear regression of the glycogen concentration time curves from 7:30-10:30 P.M. and from 10:30 P.M. to 8:00 A.M., respectively. The mean plasma glucose concentration was ~2.4-fold higher in diabetic than in nondiabetic subjects (13.6 ± 0.4 vs. 5.8 ± 0.1 mmol/l, P < 0.001). Rates of net glycogen synthesis and net glycogen breakdown were reduced by ~74% (0.11 ± 0.02 vs. 0.43 ± 0.04 mmol/l liver/min, P < 0.001) and by ~47% (0.10 ± 0.01 vs. 0.19 ± 0.01 mmol/l liver/min, P < 0.001) in diabetic patients, respectively. During short-term (24-h) intensified insulin treatment, the mean plasma glucose level was not different between diabetic and nondiabetic subjects (6.4 ± 0.1 mmol/l). Net glycogen synthesis and breakdown increased by ~92% (0.23 ± 0.04 mmol/l liver/min, P = 0.017) and by ~40% (0.14 ± 0.01 mmol/l liver/min, P = 0.011), respectively. In conclusion, poorly controlled type 1 diabetic patients present with marked reduction in both hepatic glycogen synthesis and breakdown. Both defects in glycogen metabolism are improved but not normalized by short-term restoration of insulinemia and glycemia.


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