Diabetes, obesity & metabolism · 2025
Persisting plasma proinsulin levels in a cohort of 482 individuals with long-standing type 1 diabetes mellitus.
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de Wit Douwe Frank, Fuhri Snethlage Coco Marjolein, Minab Rana, Rampanelli Elena, de Groen Pleun, Balvers Manon, McDonald Timothy James, Oram Richard A, Roep Bart O, van Raalte Daniel H, Verchere Cameron Bruce, Nieuwdorp Max, Hanssen Nordin M J
Аннотация
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.
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.