Proinsulin levels and the proinsulin:c-peptide ratio complement autoantibody measurement for predicting type 1 diabetes.
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.
Truyen
I
I
Diabetes Research Center, Brussels Free University-VUB, Brussels, Belgium.
De Pauw
P
P
Jørgensen
P N
PN
Van Schravendijk
C
C
Ubani
O
O
Decochez
K
K
Vandemeulebroucke
E
E
Weets
I
I
Mao
R
R
Pipeleers
D G
DG
Gorus
F K
FK
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*
D001323:Autoantibodies; D002096:C-Peptide; D006683:HLA-DQ Antigens; D006728:Hormones; C096322:ICA512 autoantibody; D011384:Proinsulin