Elevated Proinsulin Levels Related to Islet Cell Antibodies in First-Degree Relatives of IDDM Patients

Abstract

Objective To assess whether proinsulin levels are elevated in first-degree relatives of insulin-dependent diabetes mellitus (IDDM) patients and whether there is a relationship between proinsulin levels and the occurrence of immunological markers. Research Design and Methods Fasting proinsulin concentrations were measured in 85 first-degree relatives (54 siblings, 20 parents, 11 children) of IDDM patients and in 90 age- and weight-matched control subjects with no family history of diabetes mellitus. Results Fasting proinsulin levels (median, 25th, and 75th percentiles) were 8 pM (range 3.2–14 pM) in first-degree relatives and 1.7 pM (range 1.7–4 pM) in control subjects (P P P P = 0.04) compared with control subjects but without differences between these groups. Islet cell antibody positive (ICA⁺) IDDM relatives had significantly higher proinsulin levels than ICA^- (16 pM; range 7.2–25 vs. 6.9 pM, range 3.1–12 pM; P = 0.02). There was no difference between individuals with and without insulin autoantibodies. No difference in proinsulin levels was observed if the relatives were subdivided according to HLA-DR sharing with the diabetic proband. Conclusions Fasting proinsulin concentrations were raised not only in siblings but also in parents and children of IDDM patients. Because proinsulin is more elevated in ICA⁺ than in ICA⁻ subjects, increased proinsulin levels could reflect minor β-cell damage due to previous immunological attack.