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.
Original language | English |
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Pages (from-to) | 2322-2329 |
Number of pages | 8 |
Journal | Diabetologia |
Volume | 48 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2005 |
Keywords
- Adult
- Autoantibodies/blood
- C-Peptide/blood
- Child
- Child, Preschool
- Diabetes Mellitus, Type 1/blood
- Female
- HLA-DQ Antigens/genetics
- Hormones/blood
- Humans
- Infant
- Infant, Newborn
- Islets of Langerhans/immunology
- Male
- Middle Aged
- Pedigree
- Prediabetic State/diagnosis
- Predictive Value of Tests
- Proinsulin/blood