title: Proinsulin levels and the proinsulin:c-peptide ratio complement autoantibody measurement for predicting type 1 diabetes.
abstract: OBJECTIVE
  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.
  
  
  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
  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.affiliation: Diabetes Research Center, Brussels Free University-VUB, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Truyen
authors.forename: P
authors.initials: P
authors.lastname: De Pauw
authors.forename: P N
authors.initials: PN
authors.lastname: Jørgensen
authors.forename: C
authors.initials: C
authors.lastname: Van Schravendijk
authors.forename: O
authors.initials: O
authors.lastname: Ubani
authors.forename: K
authors.initials: K
authors.lastname: Decochez
authors.forename: E
authors.initials: E
authors.lastname: Vandemeulebroucke
authors.forename: I
authors.initials: I
authors.lastname: Weets
authors.forename: R
authors.initials: R
authors.lastname: Mao
authors.forename: D G
authors.initials: DG
authors.lastname: Pipeleers
authors.forename: F K
authors.initials: FK
authors.lastname: Gorus
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics; D006728:Hormones / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011236:Prediabetic State / Q000175:diagnosis / Q000378:metabolism; D011237:Predictive Value of Tests; D011384:Proinsulin / Q000097:blood*
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D006683:HLA-DQ Antigens; D006728:Hormones; C096322:ICA512 autoantibody; D011384:Proinsulin