Reduced Urinary Insulin Clearance in Patient With Abnormal Insulinemia

We recently reported a new case of abnormal insulinemia with Leu^A3 insulin. Herein, we measured urinary insulin clearance during oral glucose tolerance tests in a proband with abnormal insulinemia (44-yr-old female), three affected family members, two unaffected family members, two other hyperinsulinemic patients with obesity, five non-insulin-dependent diabetic patients, and five normal control subjects. Urinary insulin-to-creatinine clearance ratio in the proband and her affected family members was 0.22 × 10⁻³ ± 0.07 (mean ± SD, n = 4) and was markedly reduced compared with those of other groups: 1.73 × 10⁻³ in two unaffected family members, 2.77 × 10⁻³ in two other hyperinsulinemic patients with obesity, 2.99 × 10⁻³ ± 1.48 in five non-insulin-dependent diabetic patients, and 2.54 × 10⁻³ ± 0.67 in five normal control subjects. In contrast, urinary C-peptide clearance in these groups was not significantly different from controls. Binding of immunopurified insulins extracted from urine of the patients with abnormal insulinemia to guinea pig kidney membrane was slightly decreased (71% of standard insulin), in contrast with the observation that serum insulin of the proband had much less receptor-binding activity. Reverse-phase HPLC analysis of the immunopurified insulin of the proband revealed that the ratios of normal insulin to abnormal insulin were 8:3 in urine and 1:7 in serum, respectively. These results suggest that excretion of abnormal insulin in urine is much less than that of normal insulin.