Effects of short-term improvement of insulin treatment and glycemia on hepatic glycogen metabolism in type 1 diabetes

Insufficiently treated type 1 diabetic patients exhibit inappropriate postp randial hyperglycemia and reduction in liver glycogen stores. To examine th e effect of acute improvement of metabolic control on hepatic glycogen meta bolism, lean young type 1 diabetic (HbA(1c) 8.8 +/- 0.3%) and matched nondi abetic 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 C-13 nuclear magnetic resonance spe ctroscopy. Rates of net glycogen synthesis and breakdown mere calculated fr om 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 gl ucose concentration was similar to2.4-fold higher in diabetic than in nondi abetic 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 <similar to>74% (0.11 +/- 0.02 vs. 0.43 +/- 0.04 mmol/l liver/min, P < 0.001) and by <similar to>47% (0.10 +/- 0.01 vs. 0.19 +/- 0.01 mmol/l liver/min, P < 0.0 01) in diabetic patients, respectively. During short-term (24-h) intensifie d insulin treatment, the mean plasma glucose level was not different betwee n diabetic and nondiabetic subjects (6.4 +/- 0.1 mmol/l). Net glycogen synt hesis and breakdown increased by <similar to>92% (0.23 +/- 0.04 mmol/l live r/min, P = 0.017) and by similar to 40% (0.14 +/- 0.01 mmol/l liver/min, P = 0.011), respectively. In conclusion, poorly controlled type 1 diabetic pa tients present with marked reduction in both hepatic glycogen synthesis and breakdown. Both defects in glycogen metabolism are improved but not normal ized by short-term restoration of insulinemia and glycemia.