A new case of familial hyperproinsulinemia

We reported a case with increased serum immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR). The molar ratio of IRI to CPR was also increased. The propositus was diabetic with background retinopathy and neuropathy. No antibody to insulin or insulin receptor was detected in his serum and his insulin resistance was not so remarkable. When the serum was fractionated by gel filtration, about 90% of total IRI was recovered in the fraction where biosynthetic human proinsulin was eluted. The major part of the CPR was also recovered in the same fraction as proinsulin-like material. His daughter, 28 years old, a non-obese female, also had high IRI, CPR and a high molar ratio of IRI to CPR. A gel filtration study demonstrated the same elution profile as the propositus. Tryptic digestion failed to convert the proinsulin-like material from the propositus to insulin in a sufficient quantity to convert human proinsulin to insulin. These data strongly suggest that this family is a new case of familial hyperproinsulinemia, and the defect resides in the proinsulin molecule, not in the converting enzymes.