Clinical Information (ข้อมูลทางคลินิก):
Proinsulin is the precursor of insulin and C-peptide (connecting peptide). Following synthesis, proinsulin is packaged into secretory granules, where it is processed to C-peptide and insulin by prohormone convertases (PC1/3 and PC2) and carboxypeptidase E. Only 1% to 3% of proinsulin is secreted intact. However, because proinsulin has a longer half-life than insulin, circulating proinsulin concentrations are in the range of 5% to 30% of circulating insulin concentrations on a molar basis, with the higher relative proportions seen after meals and in patients with insulin resistance or early type 2 diabetes. Proinsulin can bind to the insulin receptor and exhibits 5% to 10% of the metabolic activity of insulin.
Interpretation (การแปลผล):
Normal individuals will have proinsulin concentrations below the upper limit of the normal fasting reference range (22 pmol/L) when hypoglycemic (blood glucose <60 mg/dL). Conversely, most (>80%) insulinoma patients will have proinsulin concentrations above the upper limit of the reference range. The sensitivity and specificity for a diagnosis of insulinoma during hypoglycemia are approximately 75% and near 100%, respectively, at the 22 pmol/L cutoff. A higher sensitivity (>95%) can be achieved using a 5 pmol/L cutoff, which is recommended by Mayo Clinic's highly-experienced hypoglycemia team to avoid missing cases. However, the lower cutoff results in reduced specificity (approximately 40%), emphasizing the need for a combination of different tests to assure accurate biochemical diagnosis.
Patients with prohormone convertase 1/3 deficiency have low, or sometimes undetectable, insulin levels and substantially elevated proinsulin levels, exceeding the upper limit of the reference range substantially in the fasting state and rising even higher after food intake. Many other hormonal abnormalities are also present, including cortisol deficiency (because of lack of processing of pro-opiomelanocortin to adrenocorticotropic hormone and other peptides), infertility, and, often, obesity.
Cautions
To avoid misdiagnoses, all proinsulin measurements used in the diagnostic workup of patients with hypoglycemia must be interpreted in the context of coexisting illnesses, blood glucose concentration at the time of sampling, and other tests, namely, insulin, C-peptide, beta-hydroxybutyrate measurements, and a sulfonylurea drug screen.
Patients with chronic kidney failure and type 2 diabetes mellitus can have increased proinsulin, C-peptide, and insulin values but usually without suppressed (<45 mg/dL) blood glucose concentrations.