Haeften, Timon W. van

To assess the possible influence of moderate titer insulin antibodies on diabetic glycemic control, we examined insulin-antibody equilibrium binding characteristics, postprandial glucose tolerance, and plasma free-insulin profiles after subcutaneous injection of both porcine and human insulin (0.15 U/kg) in 12 patients with insulin-dependent diabetes mellitus under conditions simulating intensive insulin therapy. The patients' antibodies bound porcine and human insulin indistinguishably, and their plasma glucose and freeinsulin profiles after ingestion of a standard meal were similar with both insulins. Initial increases in plasma free-insulin levels after injection of both insulins were negatively correlated with both insulin-antibody binding (r = −.55, P < .006) and postprandial hyperglycemia (peak level r = −.56, P < .006); the latter was positively correlated with insulin-antibody binding (r = .48, P < .02). The effects of insulin antibodies on postprandial plasma free-insulin and glucose levels could be accounted for substantially by the association constant of the high-affinity insulin-antibody binding sites (K1); patients in the highest quartile for K1 had significantly slower initial increments in plasma free insulin (0.31 ± 0.04 vs. 0.46 ± 0.06 μU/min, P < .05) and greater postprandial hyperglycemia (peak value 237 ± 10 vs. 166 ± 12 mg/dl, P < .001) than patients in the lowest quartile. We conclude that moderate insulin-antibody titers commonly found in insulin-treated patients can slow the early increase in plasma free insulin after subcutaneous injection and that this impairs postprandial glucose tolerance; such an effect may Received for publication 22 April 1986 and accepted in revised form 18 September 1986. limit the effectiveness of intensive insulin therapy.

Fasting hypoglycemia, which persisted for 3 days after insulin treatment was stopped,occurred in a patient with non-insulin-dependent diabetes mellitus who had inappropriate plasma free-insulin levels (18–25 μU/ml) and extremely high antibody-bound insulin (>20,000 μU/ml) but normal counterregulatory hormone secretion and plasma C-peptide levels. The amount of antibody-bound insulin decreased in a biphasic pattern over13 mo of observation with an initial half-life of 35 days and a more gradual decrease with a half-life of 160 days. The number of high-affinity antibody binding sites was virtually identical to the amount of antibody-bound insulin in the patient's plasma. We conclude that the patient's fasting hyperinsulinemia and hypoglycemia were due to release of antibody-bound insulin.