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

Abstract

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 (HbA_1c 8.8 ± 0.3%) and matched nondiabetic subjects (HbA_1c 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.