1131 EVALUATION OF THERAPY IN DIABETES MELLITUS: USE OF FREE INSULIN

Abstract

Diabetic therapy is traditionally evaluated using measurements of blood glucose regulation. The ability to measure free (unbound) insulin enables a more direct study of the relationship between insulin dose and the concentration of free insulin and metabolic parameters in blood.Eight insulin-dependent, C-peptide negative diabetics, 7 to 22 years, were given their usual dose of NPH and regular insulin, and blood samples were serially obtained for levels of free and total insulin, glucose, FFA and ketone bodies. Twenty-four hours later, a standard four hour low dose constant infusion of crystalline insulin was given. Data were analyzed using individual and integrated concentrations of hormones and substrates.In all patients, NPH insulin led to minimal increases in blood insulin (< 15 μU/ml). Low insulin concentrations were associated with elevated parameters of metabolic control. Insulin infusion led to insulin levels between 35 and 50 μU/ml at steady state, and with normalization of glucose, FFA and ketone bodies. A significant reduction in serum [K+] occurred during insulin infusion.These data suggest that: 1) long-acting insulin produces minimal increases in serum insulin; 2) measurement of free insulin can be used to distinguish inadequate insulin dose or aberrant absorption from insulin resistance; 3) conventional NPH therapy cannot lead to adequate metabolic control; 4) hypokalemia may be a marker for states of excess insulin administration.