IMPAIRED NET HEPATIC GLYCOGEN-SYNTHESIS IN INSULIN-DEPENDENT DIABETICSUBJECTS DURING MIXED MEAL INGESTION - A C-13 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY STUDY

Hepatic glycogen concentration was measured in six subjects with insul in-dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using C-13 nuclear magnetic resonance spectroscopy during a d ay in which three isocaloric mixed meals were ingested. The relative f luxes of the direct and indirect (3 carbon units --> --> glycogen) pat hways of hepatic glycogen synthesis were also assessed using [1-C-13]g lucose in combination with acetaminophen to noninvasively sample the h epatic UDP-glucose pool. Mean fasting hepatic glycogen content was sim ilar in the two groups. After each meal, hepatic glycogen content incr eased, peaking 4-5 h after the meal in both groups. By 11:00 p.m. the IDDM subjects had synthesized only 30% of the glycogen that was synthe sized by the control group [IDDM subjects, net increment = 44 +/- 20 ( mean +/- SE) mM; control subjects, net increment = 144 +/- 14 mM; P < 0.05]. After breakfast the flux through the gluconeogenic pathway rela tive to the direct pathway of hepatic glycogen synthesis was 1.7-fold greater in the IDDM subjects (59 +/- 4%) than in the control subjects (35 +/- 4%, P < 0.0003). In conclusion, under mixed meal conditions, s ubjects with poorly controlled IDDM have a major defect in net hepatic glycogen synthesis and augmented hepatic gluconeogenesis. The former abnormality may result in an impaired glycemic response to counterregu latory hormones, whereas both abnormalities may contribute to postpran dial hyperglycemia.