Increased Insulin Binding to Erythrocytes in Diabetic Ketoacidosis: Normalization with Insulin Therapy*

We studied insulin binding to erythrocytes in eight male type I diabetic patients in diabetic ketoacidosis (DKA) before and 24 h and 5 days after low dose insulin treatment. Mean specific [125I]insulin binding in DKA (mean +/- SEM, 13.3 +/- 0.6%) was significantly higher than values 24 h and 5 days after treatment (10.7 +/- 0.7% and 9.6 +/- 0.4%, respectively; P less than 0.001). These values after treatment were similar to those of 15 age-matched normal males (10.5 +/- 0.4%) and 6 controlled type I diabetic patients (10.1 +/- 0.7%). The affinity constant (Ka = 2.26 +/- 0.12 10(9) M-1) was significantly higher in DKA patients than in normal subjects (1.75 +/- 0.15 10(9) M-1) or type I controlled diabetics (1.55 +/- 0.15 10(9) M-1; P less than 0.01). Insulin binding correlated inversely with arterial pH (r = -0.80; P less than 0.001; n = 8). These results indicate an increase in specific [125I]insulin binding to erythrocytes in DKA, which is due to elevated receptor affinity (but not receptor numbers) and is reversible with treatment.