In RMS severe insulin resistance is caused by defective insulin receptors. This patient lacks insulin receptor binding due to a truncation of one allele and a point mutation of the other allele of the ( subunit. He developed pulmonary hypertension and cor-pulmonale and was considered for lung transplantation. A trial of Prednisone was initiated to determine if he could tolerate immuno-suppressive therapy. We studied carbohydrate metabolism at baseline (BL) and after four days of glucocorticoid therapy (GC). Each study was preceded by 24 hr of intravenous insulin to maintain plasma glucose (PG) at 150-200 mg/dl and a 12 hr fast. A primed continuous infusion of 6,6-2H2-glucose was started 2 hr before each study following which insulin was off for 2 hr (OFF) and resumed at 7 units/kg/hr for 2 hr. Dextrose was infused as needed to maintain PG at 170 mg/dl (CLAMP). Total glucose utilization did not change in response to large doses of exogenous insulin at BL or GC, indicat ing complete peripheral insulin resistance. HGP was partially suppressed during BL-CLAMP, indicating partial hepatic sensitivity to insulin. During GC, HGP failed to suppress despite similar free insulin levels, indicating that GC worsened hepatic insulin resistance. The effect of insulin on the liver in this insulin resistant state may be due to residual activity of the patient's defective insulin receptor, cross reactivity with the IGF-1 receptor or a non-insulin-mediated process. Regardless, this process appears to be blocked by glucocorticoids.
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