Identification of Surrogate Biomarkers for the Prediction of Patients at Risk of Low Macular Pigment in Type 2 Diabetes

Abstract

Purpose: This cross-sectional study compared macular pigment (MP) levels among persons with Type 2 diabetes relative to healthy controls. Additionally, a range of behavioral, anthropometric, clinical and serum measures were explored as possible predictors of low MP optical density (MPOD) in diabetes. Methods: Two health status groups; Group 1: Type 2 diabetes (n = 188), and Group 2: Healthy controls (n = 2,594) completed a full MP assessment using customized heterochromatic flicker photometry, as part of The Irish Longitudinal Study on Aging (TILDA). Clinical [blood pressure; cataract status; MPOD] and anthropometric [waist (cm); weight (kg); hip (cm)] measurements were taken, and a blood sample drawn for analysis of serum biomarkers [lipoproteins; inflammatory markers (C reactive protein and vitamin-D)]. Results: One-way ANOVA revealed lower MPOD in subjects with Type 2 diabetes relative to controls (p = .047). Amongst participants with diabetes, those with low serum vitamin D (≤50 nmol/L) had significantly lower mean MPOD compared to those with sufficient serum vitamin D levels >50 nmol/L (0.173(0.148) vs. 0.226(0.145); p = .006). Concomitantly, MP was significantly lower in diabetes participants with raised serum triglyceride (TG) to high density lipoprotein (HDL) ratio (TG/HDL); values >1.74 mmol/L (0.172 (0.140) vs 0.215 (0.152); p = .039). Body mass index, waist-to-height ratio and waist circumference, were all significantly negatively correlated with MPOD (Pearson's correlation, p < .05 for all). Significant correlates of MPOD in the multivariate regression model included smoking, cataract, and vitamin D, which collectively contributed 18.5% of the overall variability in MPOD status amongst participants with Type 2 diabetes. Conclusions: This study provides additional evidence that low MP may indeed be a feature of Type 2 diabetes, and further identifies smoking, cataract and vitamin D status as plausible predictors of low MPOD amongst persons with Type 2 diabetes.

A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy

“…Clinical studies implicate MPOD depletion, as well as low serum levels of lutein and zeaxanthin, may represent a novel clinical feature of DR; one that is likely contingent upon several metabolic perturbations associated with chronic hyperglycemia in type 1 and type 2 diabetes. Reports from observational studies are consistent in demonstrating carotenoid levels (measured both in serum and the macular pigment) are further reduced among diabetic patients with clinically evident retinopathy ( Table 3 ) [ 19 , 25 , 34 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ]. In fact, one study found that lower plasma concentrations of lutein and zeaxanthin were significantly associated with greater risk of incident maculopathy as well as disease progression in patients with T2DM [ 109 ].…”

“…Consequently, 103 records were excluded based on article type, with an additional 148 records excluded due to the aforementioned inclusion criteria for clinical and preclinical studies. Finally, 30 records were identified to be eligible for full-text assessment, of which, 18 studies were included in the final review: seven preclinical studies [ 102 , 103 , 104 , 105 , 106 , 107 , 108 ], nine observational clinical studies [ 19 , 25 , 109 , 110 , 111 , 112 , 113 , 114 , 115 ] and two interventional clinical trials [ 34 , 116 ].…”

“…Inherent defense mechanisms against oxidative damage in the retina involve constant neutralization of reactive oxygen species (ROS). Congruously, both endogenous and exogenous antioxidants are essential in maintaining cellular redox homeostasis [ 20 , 25 , 26 ]. Quite appropriately, it is postulated that the interdependence between prolonged hyperglycemia, oxidative stress, and changes in redox homeostasis is a key factor contributing to the pathogenesis of diabetic retinopathy [ 19 , 25 ].…”

“…They belong to the xanthophyll class of carotenoids which contain oxygen in their polyene chain structure and are more lipophilic in comparison with the other subgroup of carotenoids known as carotenes, which do not contain oxygen and are purely hydrocarbons [ 27 , 31 ]. Three isomeric xanthophyll carotenoids—lutein, zeaxanthin, and meso -zeaxanthin ( Figure 1 )—are believed to possess significant antioxidant and anti-inflammatory properties in the retina and have been shown to benefit in prevention of age-related macular degeneration (AMD) [ 25 , 27 , 32 , 33 , 34 , 35 ]. Oxidative insult contributing to retinal neurodegeneration is common to the pathogenesis of both DR and AMD.…”

Occurrence and Determination of Carotenoids and Polyphenols in Different Paprika Powders from Organic and Conventional Production

“…They can be used in food as spices, colorants, and antioxidant agents [ 9 , 10 , 11 ]. Moreover, carotenoids have healthful properties and can prevent chronic diseases such as different kinds of cancer, cardiovascular disease, type 2 diabetes, and atherosclerosis [ 12 , 13 , 14 ]. Many studies have shown that organic vegetables contain more bioactive compounds, including carotenoids, than conventionally grown vegetables [ 15 , 16 , 17 , 18 ].…”