Carbohydrate (CHO) Oxidation in Patients with Type B Insulin Resistance

Total body carbohydrate (CHO) and fat oxidation rates, plasma glucose, free fatty acid, and insulin concentrations were determined in two patients with the type B syndrome of severe insulin resistance and in normal controls in response to insulin infusions (1–100 mil/kg/min) and to a test meal. In addition, insulin was infused at higher rates (10–1000 mU/kg/min) in one of the two patients while plasma glucose concentrations were clamped first at 195 and later at 244 mg/dl. During the postabsorptive state, resting metabolic rates (RMR) were 914 and 979 cal/min/1.73 m² in the two patients (controls: 1018 ± 85 cal/min/1.73 m²). Patients met 85% and 83% of their caloric requirements by oxidizing fat (controls: 63 ± 7%). Protein oxidation accounted for 15% and 13% (controls: 14 ± 3%) of energy requirements and CHO oxidation for 0% and 0%, respectively, in both patients (controls: 23 ± 5%). Infusion of insulin at a rate of 10 mU/kg/min raised plasma insulin concentrations from 1400 and 440 nil/ml to 6000 and 2500 (μU/ml, respectively, in patients 1 and 2 (controls: from 4 ± 0.3 to 1288 ± 50 μU/ml), but had no effects on rates of CHO, fat, or protein oxidation in either patient. By comparison, the rate of CHO oxidation in controls rose about sixfold from 40 ± 8 to 234 ± 12 mg/min/1.73 m². Infusion of 1000 mU/kg/min in combination with an increase in plasma glucose from 195 ± 1.1 to 244 ±1.9 mg/dl in patient 1, however, raised CHO oxidation from 0 to 36 mg/min/1.73 m² and lowered fat oxidation from 105 to 69 mg/min/1.73 m². In response to a test meal, rates of CHO oxidation rose from 49 ± 9 to 193 ± 3 mg/min/1.73 m² in controls, from 24 to 67 mg/min/1.73 m² in patient 1, and remained 0 mg/min/1.73 m² in patient 2. We conclude that presence of anti-insulin receptor antibodies (AIRA) suppressed postabsorptive as well as insulin and meal stimulation of CHO oxidation. The depression of CHO oxidation persisted even in the presence of normal or increased rates of glucose disappearance. As a result, patients with AIRA rely predominantly on fat oxidation to meet their normal caloric requirements.