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01.11.2005 | Article

Proinsulin levels and the proinsulin:c-peptide ratio complement autoantibody measurement for predicting type 1 diabetes

verfasst von: I. Truyen, P. De Pauw, P. N. Jørgensen, C. Van Schravendijk, O. Ubani, K. Decochez, E. Vandemeulebroucke, I. Weets, R. Mao, D. G. Pipeleers, F. K. Gorus, The Belgian Diabetes Registry

Erschienen in: Diabetologia | Ausgabe 11/2005

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Abstract

Aims/hypothesis

We investigated whether random proinsulin levels and proinsulin:C-peptide ratio (PI:C) complement immune and genetic markers for identifying relatives at high risk of type 1 diabetes.

Materials and methods

During an initial sampling, random glycaemia, proinsulin, PI:C and HLA DQ genotype were determined in 561 non-diabetic first-degree relatives who had been positive for islet autoantibodies on one or more occasions and in 561 age- and sex-matched persistently antibody-negative relatives.

Results

During follow-up (median 62 months), 46 relatives with antibodies at entry developed type 1 diabetes. At baseline, antibody-positive relatives (n=338) had higher PI:C values (p<0.001) than antibody-negative subjects with (n=223) or subjects without (n=561) later seroconversion. Proinsulin and PI:C were graded according to risk of diabetes as expressed by positivity for (multiple) antibodies or IA-2 antibodies, especially in persons carrying the high-risk HLA DQ2/DQ8 genotype and in prediabetic relatives. In the presence of multiple or IA-2 antibodies, a PI:C ratio exceeding percentile 66 of all antibody-negative relatives at entry (n=784) conferred a 5-year diabetes risk of 50% and 68%, respectively (p<0.001 vs 13% for same antibody status with PI:C<percentile 66). Cox regression analysis confirmed random PI:C as an independent predictor of the risk of diabetes (p≤0.001).

Conclusions/interpretation

Random proinsulin and PI:C represent dynamic markers of the state of beta cell function that complement immune markers in identifying relatives who are at homogeneously high risk of contracting type 1 diabetes and are therefore eligible for secondary prevention trials.

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Titel: Proinsulin levels and the proinsulin:c-peptide ratio complement autoantibody measurement for predicting type 1 diabetes
verfasst von: I. Truyen
P. De Pauw
P. N. Jørgensen
C. Van Schravendijk
O. Ubani
K. Decochez
E. Vandemeulebroucke
I. Weets
R. Mao
D. G. Pipeleers
F. K. Gorus
The Belgian Diabetes Registry
Publikationsdatum: 01.11.2005
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 11/2005
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-005-1959-0

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Proinsulin levels and the proinsulin:c-peptide ratio complement autoantibody measurement for predicting type 1 diabetes

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Materials and methods

Results

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