OVERNIGHT GLUCOSE-METABOLISM IN OBESE NON-INSULIN-DEPENDENT DIABETIC-PATIENTS AND IN HEALTHY LEAN INDIVIDUALS

Increased fasting hepatic glucose production is present in NIDDM patie nts, and has been shown to be due to increased gluconeogenesis. In ord er to determine the contribution of the cycling between glucose and th ree-carbon compounds (Cori and glucose-alanine cycles) to the increase d hepatic glucose production, glucose kinetics measured overnight in s even obese NIDDM patients and six lean healthy subjects with both 6,6 H-2 glucose and U-C-13 glucose were determined. At 0500 h obese NIDDM subjects showed a 40% increase in glucose appearance calculated from 6 ,6 H-2 glucose, whereas glucose appearance calculated from U-C-13 gluc ose was similar compared to lean subjects, indicating increased glucos e cycling. Non-oxidative glucose disposal was also increased three-fol d in NIDDM patients. Glucose cycling was increased by 111% in NIDDM pa tients (118+/-18 mu mole min(-1) vs. 56+/-11 in controls, P<O.05) and was positively correlated with plasma glucose concentration (r=0.831, P<O.001) and with non-oxidative glucose disposal (r=0.714, P<O.01). Fo ur NIDDM patients were studied again after 3 days of insulin therapy. Insulin restored near-normoglycaemia (7.4+/-0.8 mmole 1(-1)) and norma lized rates of glucose appearance and glucose cycling. It is concluded that increased glucose cycling in obese NIDDM patients accounts for a major part of the increased fasting hepatic glucose production and no n-oxidative glucose disposal in obese NIDDM subjects.