The metabolic clearance rate of glucose (MCR) has been widely used to compare glucose disposal rates in subjects studied at different plasma glucose levels. This approach assumes that the glucose disposal rate varies linearly with the prevailing glucose concentration. In the present study the relationship between MCR and the serum glucose concentration was assessed in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM). Glucose clamp studies were performed in each subject at the patient's fasting glucose concentration (mean = 280 ± 17 mg/dl) and at euglycemia (mean glucose level = 85 ±3 mg/dl) in the presence of a maximally effective steady-state serum insulin concentration (∼11,000 μU/ml). Six subjects were also studied at hyperglycemia and euglycemia at a steady-state insulin concentration of ∼400 μU/ml. As expected, glucose disposal rates were significantly greater in the presence of hyperglycemia as compared with euglycemia (415 ± 28 versus 193 ± 30 mg/M2/min at the higher insulin level and 377±35 versus 162 ± 26 mg/M2/min at the lower insulin level). The mean MCR for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglyglycemia. Thus at hyperglycemia the mean MCR fell by 34% and 36% at the higher and lower insulin levels, respectively. When the individual data were analyzed, a highly significant positive relationship (r = −0.88, P < 0.001) was found between the magnitude of the MCR value at euglycemia and the degree of fall in MCR at hyperglycemia. Thus, the greater the insulin resistance (lower MCR at euglycemia), the smaller the reduction in MCR at hyperglycemia. These results indicate that (1) the metabolic clearance rate of glucose is not independent of changes in the serum glucose concentration, indicating that even in the presence of maximally effective insulin concentrations glucose uptake by peripheral tissues is a saturable process and (2) as type II diabetic patients become less insulin resistant, their glucose uptake mechanisms become more saturable.

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