Abstract
Aims/HypothesisHLA 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.MethodsThe 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.ResultsThe 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.ConclusionsIncreased 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.
Highlights
The World Health Organization estimates that more than 180 million people worldwide have diabetes mellitus and this number is likely to more than double by 2030; about 10% have type 1 diabetes mellitus [1]
In this study we hypothesize that autoimmune processes resulting from HLA genotype and the relationship of these genes with islet autoantibody status and residual C-peptide production at the clinical onset of diabetes are associated with the risk of diabetic retinopathy (DR) 15 years later
Type 1 diabetes begins as an autoimmune process that can be differentiated from type 2 diabetes by the presence of islet autoantibodies before [6,7,8] and at the time of clinical onset
Summary
The World Health Organization estimates that more than 180 million people worldwide have diabetes mellitus and this number is likely to more than double by 2030; about 10% have type 1 diabetes mellitus [1]. Type 1 diabetes begins as an autoimmune process that can be differentiated from type 2 diabetes by the presence of islet autoantibodies before [6,7,8] and at the time of clinical onset [9,10] These include islet cell autoantibodies (ICA) [11,12,13] and autoantibodies against specific autoantigens including the 65 kD isoform of glutamic acid decarboxylase (GADA) [14,15,16], insulinoma-antigen 2 (IA-2A) [17,18,19], insulin (IAA) [20], and the cation efflux transporter ZnT8 (ZnT8A) [21]. There is typically a continuous decline as the disease progress [27] which is associated with the number and types of islet autoantibodies present [28]
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