Prominent Hyperproinsulinemia in a Middle Age Patient

Insulin is synthesized in the β-cells from preproinsulin. Preproinsulin becomes proinsulin after leaving the signal peptide. Proinsulin is separated into C-peptide and insulin by 2 enzymes. Hyperproinsulinemia is suspected to be a pancreatic β-cell defect that is augmented by the increased demand placed on the β-cell by hyperglycemia.

A 39-year-old Japanese man visited to Shin-suma hospital in May 2013. Liver dysfunction, dyslipidemia, and hyperuricemia had been found in medical checkups in his workplace. Therefore, he visited Shin-suma hospital in order to receive intensive examination. Diet and exercise therapy were initiated. In November 2013, intact proinsulin and proinsulin per insulin (PI/I) ratio were evaluated as part of an ongoing study. His intact proinsulin level and PI/I ratio were markedly elevated. A 75 g oral OGTT revealed that his glucose tolerance was impaired. His glycosylated hemoglobin was 6.9%. He was diagnosed as having type 2 diabetes mellitus. Although, diet and exercise therapy continued, his hyperproinslinemia and diabetes mellitus remained. Therefore, aloguliptin was started in order to recover insulin secretion in November 2014. Thereafter, pioglitazone was added to improve insulin resistance. Finally, luseogliflozin was commenced to expect glucose-lowering effects. His HbA1c was stabilized. To the best of our knowledge, there have been few reports of patients with hyperproinsulinemia.

When the physicians face treatment resistance in diabetes mellitus, we emphasize that evaluation of proinsulin should be considered as one of the methods.