It has recently been shown that conventionally treated IDDMs are insulin resistant. Using the insulin clamp technique, we studied the influence of metabolic status on the in vivo insulin effect in these patients. Eleven IDDMs, treated conventionally with diet and insulin for 10.7 ± 5.6 yr, were studied before and after continuous subcutaneous insulin infusion (CSII) treatment (with a portable pump) for 6 mo. We found that conventionally treated diabetic subjects were extremely insulin resistant with regard to peripheral glucose uptake. Glucose uptake, at an insulin concentration of about 80 μU/ml, was 4.3 ± 2.0 mg/kg · min before treatment compared with 11.5 ± 4.0 mg/kg · min in normals (P < 0.01). After pump treatment for 6 mo, metabolic control improved significantly (HbA1c decreased from 8.9 ± 1.9% to 7.4 ± 1.2%, P < 0.01) and, parallel to that, glucose uptake increased about 80% to 7.5 ± 3.5 mg/kg · min (P < 0.01). The mean daily plasma FFA level decreased from 0.32 ± 0.10 mmol/L to 0.21 ± 0.07 mmol/L (P < 0.01); this variable was negatively correlated to the glucose clearance rate (r = –0.62, P < 0.01). There was no statistically significant change in mean daily plasma insulin and plasma growth hormone levels or in 24-h cortisol excretion in the urine (P > 0.1). The insulin binding capacity of serum IgG was also unchanged, and there was no significant relationship between this quantity and glucose clearance rates (r = 0.18, P > 0.1). We conclude that conventionally treated IDDMs are insulin resistant with regard to peripheral glucose uptake. The insulin resistance may, at least in part, be secondary to the abnormal metabolic Status Of these patients.

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