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

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< or =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.

• Authors: 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, Belgian Diabetes Registry
• Journal: Diabetologia (Diabetologia) Vol. 48 Issue 11 Pg. 2322-9 (Nov 2005) ISSN: 0012-186X [Print] Germany
• PMID: 16211374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• C-Peptide
• HLA-DQ Antigens
• Hormones
• ICA512 autoantibody
• Proinsulin

Topics

• Adult
• Autoantibodies (blood)
• C-Peptide (blood)
• Child
• Child, Preschool
• Diabetes Mellitus, Type 1 (blood, diagnosis)
• Female
• HLA-DQ Antigens (genetics)
• Hormones (blood)
• Humans
• Infant
• Infant, Newborn
• Islets of Langerhans (immunology)
• Male
• Middle Aged
• Pedigree
• Prediabetic State (diagnosis, metabolism)
• Predictive Value of Tests
• Proinsulin (blood)