A Prospective Study of Type 1 and Type 2 Diabetics Examining the Correlation Between Antioxidant Levels and Neuronal Layer Loss (DECAN)

Abstract

Diabetic retinopathy has long been considered as a microvascular disease of the retina with complex pathways that contribute to the pathogenesis. There is significant evidence for the role of oxidative stress development of diabetic retinopathy and there is increasing interest in the role of antioxidant micronutrients in the prevention of diabetic complications. There is also growing evidence from clinical and laboratory studies to support neuronal damage in the retina of diabetic patients even before there are any fundal changes clinically. Studies have also examined the associations between macular pigment optical density and glycated haemoglobin (HbA1C) in type 2 diabetics with and without retinopathy. Although various theories have been proposed about neurodegeneration in diabetic retinopathy it remains unclear to what role it plays in the development and progression of diabetic retinopathy and if there is an early detectable relationship with antioxidant intake. The aim of this study was to examine this further by examining the relationship between retinal neuronal layer changes assessed using spectral domain optical coherence tomography (SD-OCT) with dietary intake of foods. The development of diabetic retinopathy was then further explored to determine the relationship between severity of diabetic retinopathy with neuronal layer loss in individuals with type 1 and type 2 diabetes. The study also explored the relationship of HbA1C and serum lipid levels with macular pigment optical density measurements. Although a significant number of potential susceptible genes have previously been identified, the results of many studies have been limited by a number of negative findings so the exact roles in this area is still uncertain. Some potential single nucleotide polymorphisms (SNPs) were selected based on previous studies for analysis as part of this an exploratory study. 204 participants were recruited to the DECAN study. Outcome measures were dietary intake assessed using a food frequency questionnaire (FFQ), optical coherence tomography (OCT), macular pigment optical density (MOPD), glycated haemoglobin (HbA1c), serum lipids and deoxyribonucleic acid (DNA). The results of the study showed that both outer nuclear layer (ONL) and the inner nuclear layer (INL) showed statistically significant associations with Vitamin B12, Pantothenic acid, copper and selenium. Selenium was seen to be associated with a thinner INL. The ONL showed a statistically significant association with vitamin B12, indicating that an increase in Vitamin B12 results in a thicker ONL whereas an increase in pantothenic acid is also associated with a thinner ONL. At 12 months no correlations were evident between the FFQ data and severity of retinopathy or maculopathy. The study found that higher levels of MPOD values were positively associated with lower levels of triglycerides. There was no association was seen between MOPD scores, FFQ and OCT. Statistical analysis of the genotyping of 3 selected single nucleotide polymorphisms showed no statistically significant association between any of the groups. This study has added to the growing evidence that oxidative stress, antioxidants and neurodegeneration are critical factors in the pathogenies of diabetic retinopathy early on. The study showed promising results for further research that could lead to an interventional trial using a supplementation of selenium which has not been previously reported.