Persisting plasma proinsulin levels in a cohort of 482 individuals with long-standing type 1 diabetes mellitus.

Abstract

Aims: As compared with C-peptide, plasma proinsulin levels in individuals with long-standing type 1 diabetes mellitus are relatively understudied, but may serve as a marker of stressed, yet alive β-cells.

Materials and methods: We measured proinsulin and C-peptide levels (detection limit <0.15 pmol/L and <0.05 nmol/L, respectively) in a cross-sectional cohort of 482 individuals with type 1 diabetes mellitus and measured associations with diabetes duration, HLA haplotype and autoantibodies.

Results: Proinsulin showed a biphasic decline with an initial decrease over 15 years followed by a stabilisation period, whereas C-peptide showed a similar pattern but with an inflection point at ~8 years. Proinsulin and the proinsulin-to-C-peptide ratio did not associate with variables associated with insulin resistance (BMI, triglyceride levels, insulin/day/kg). Higher proinsulin- and C-peptide levels correlated with higher levels of anti-GAD antibodies (Spearman ρ = 0.18 and 0.23 respectively, p < 0.05), but not with anti-IA2. A high-risk DR3/3 HLA genotype associated with complete loss of C-peptide (OR 0.34, 95% CI 0.14-0.79) and proinsulin(OR 0.44, 95% CI 0.20-0.92).

Conclusions/interpretation: In type 1 diabetes mellitus, proinsulin levels remain detectable long after diagnosis, also in the absence of C-peptide, implying the presence of stressed, yet alive β-cells.