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

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.

Prognosis for residual islet β‐cell secretion function in young patients with newly diagnosed type 1 diabetes

“…For example, GAD levels in patients with newly diagnosed T1D were associated with worse peripheral nerve function, independent of GAD-related differences in glycemic control. 32 In addition, anti-GAD antibodies levels at the onset of T1D increased the risk of diabetic retinopathy 15 years later; 33 thus, we should stress the importance of detecting anti-GAD Nomogram for patients with newly diagnosed type 1 diabetes. To use the nomogram, the value attributed to an individual patient is located on each variable axis, and a line is drawn upwards to determine the number of points awarded for each variable.…”

GAD-65 autoantibodies and their role as biomarkers of type 1 diabetes and latent autoimmune diabetes in adults (LADA)

“…It is well established that other islet autoantibodies such as insulin autoantibodies and phogrin are highly accurate T1D risk predictors in childhood [46] and the age of detection of insulin autoantibodies in particular, exhibits close associations with age of T1D diagnosis in children [39]. In contrast, the presence of autoantibodies against GAD65 appears to be related to adult ages and also it has been reported that high GAD65 antibody titers exhibit a correlation with longer-term diabetic complications such as retinopathy, 15 years after T1D onset [47]. …”

Restoration of t cell substes of patients with type 1 diabetes mellitus by microencapsulated human umbilical cord Wharton jelly-derived mesenchymal stem cells: An in vitro study

“…Although less prevalent than type 2 (T2) diabetes (T2D), T1D usually strikes pediatric as mainly affects young patients, and strictly requires exogenous insulin supplementation. Unfortunately, though a life-saving therapy, exogenous insulin may delay but not eliminate the risk for developing secondary, chronic complications of the disease [2]. T1D is notoriously caused by autoimmune destruction of pancreatic islet β-cells.…”