A new case of abnormal insulinemia with diabetes. Reduced insulin values determined by radioreceptor assay.

A 44-yr-old Japanese woman was found to have diabetes with marked fasting hyperinsulinemia. Her fasting plasma glucose, serum insulin, and C-peptide levels were 137 mg/dl, 204 microU/ml, and 1.13 pmol/ml, respectively, and the C-peptide-to-insulin molar ratio was markedly reduced. Insulin antibodies and insulin-receptor antibodies were negative. Fasting levels of counter-insulin hormones were normal. She had normal hypoglycemic response to exogenous insulin injection. Binding of 125I-labeled insulin to erythrocytes was normal. Oral glucose-tolerance tests in eight members of her first-degree relatives revealed four members (mother, sister, brother, and daughter) with fasting hyperinsulinemia (111-314 microU/ml), and two of them (mother and sister) were overtly diabetic. Thus, the abnormality was thought to be an autosomal dominant trait. Reverse-phase high-performance liquid chromatograph analysis of immunopurified insulin obtained from her serum revealed two peaks of insulin immunoreactivity. The amount of the abnormal insulin peak was seven times greater than that of normal insulin. The abnormal insulin was eluted after bovine, human, and porcine insulins, indicating it has a more hydrophobic nature than normal human insulin. Radioreceptor assay (RRA) for serum insulin with guinea pig kidney membrane revealed that the binding activity of their serum insulin was markedly decreased. Discrepancies between the values measured by RRA and those measured by radioimmunoassay were also found in her family members with hyperinsulinemia but not in her family members without hyperinsulinemia and other hyperinsulinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)