Research Summary: HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later



HLA genes, islet autoantibodies and residual C-peptide were studied to
determine the independent association of each exposure with diabetic
retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in
15–34 year old individuals.


The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in
Sweden (DISS), which investigates incident cases of diabetes for patients
between 15 and 34 years of age. Blood samples at diagnosis were analyzed to
determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009,
fundus photographs were obtained from patient records. Study measures were
supplemented with data from the Swedish National Diabetes Registry.


The prevalence of DR was 60.2% (148/246). Autoantibodies against the
65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical
diabetes increased the risk of DR 15 years later, relative risk 1.12 for
each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates
to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43,
[95% CI 1.06 to 1.94] for participants in the highest
25th (GADA>233 WHO units/ml) and 5th percentile
(GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for
duration of diabetes, HbA1c, treated hypertension, sex, age at
diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen
2 autoantibodies, residual C-peptide and the type 1 diabetes associated
haplotypes DQ2, DQ8 and DQ6 were not associated with DR.


Increased levels of GADA at the onset of type 1 diabetes were associated with
DR 15 years later. These results, if confirmed, could provide additional
insights into the pathogenesis of the most common microvascular complication
of diabetes and lead to better risk stratification for both patient
screenings and DR treatment trials.


Publisher: Public Library of Science

Date Published: 11-March-2011

Author(s): Jensen R., Agardh E., Lernmark Å., Gudbjörnsdottir S., Smith N., Siscovick D., Törn C., von Herrath M.


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