Evaluation of Circulating Plasma VEGF-A, ET-1 and Magnesium Levels as the Predictive Markers for Proliferative Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is the most common cause for preventable blindness in India. The onset of micro and macrovascular complications in T2DM is multifactorial and difficult to predict. The status of micronutrients, several inflammatory cytokines, elevated triacylglycerols, oxidative stress etc., are being studied extensively. Hypomagnesemia plays a pivotal role in worsening of insulin resistance. Although, Vascular Endothelial Growth Factor-A (VEGF-A) and Endothelin-1 (ET-1) are known to be elevated in DR, yet few reports cite their role, especially in Indian population. In this study, we included thirty subjects with T2DM in each of the three groups namely, T2DM cases without retinopathy, Non Proliferative DR (NPDR) and Proliferative DR (PDR) retinopathy. The glycemic status, circulating plasma VEGF-A, ET-1 levels, serum magnesium and lipids were estimated and compared among the groups. An ROC was drawn to evaluate VEGF-A, ET-1 and serum magnesium levels as the predictive markers for PDR. On comparison VEGF-A, ET-1 and serum magnesium levels showed a significant difference among the three groups. PDR cases had higher circulating levels of VEGF-A, ET-1 and low serum magnesium levels when compared to others. ROC for VEGF-A and ET-1 showed an optimum cutoff of 1521 ng/ml (AUC 0.975) and 16 pg/ml (AUC 0.96) respectively. A negative ROC was drawn to check the lower cutoff limit for serum magnesium; we documented an optimum cut off of 1.7 mg/dl (AUC 0.837). ET-1, VEGF-A and serum Magnesium levels are significantly altered in PDR and can be used as the predictive markers of PDR.

Crosstalk of Magnesium and Serum Lipids in Dyslipidemia and Associated Disorders: A Systematic Review

“…Surprisingly, patients with proliferative retinopathy had higher HDL-C values ( p < 0.05). TC, TG, LDL-C, and VLDL concentrations did not differ significantly among the study groups [ 64 ]. Hruby et al (2017) studied the link between the intake of Mg and the risk of T2DM in three cohorts from the United States of America, detecting a 15% T2DM-risk reduction in individuals with a higher dietary intake of Mg. Hypercholesterolemia was more frequent in the fifth (12.7% for 427–498 mg/day) versus first (8.7% for 242–275 mg/day) quartile of Mg intake, whereas in women the data were conflicting: in one cohort, hypercholesterolemia was more prevalent in the fifth (7.8% for 357–418 mg/day) versus first (6.2% for 187–218 mg/day) quartile of Mg intake, whereas in the other cohort the results were opposite (15.4% for 213–245 mg/day versus 14.4% for 385–448 mg/day) [ 65 ].…”

Pathological Hyperinsulinemia and Hyperglycemia in the Impaired Glucose Tolerance Stage Mediate Endothelial Dysfunction Through miR-21, PTEN/AKT/eNOS, and MARK/ET-1 Pathways

“…Insulin was initially believed to be a vasodilator because of its activation on NO secretion (30,31). However, in recent studies, insulin-induced vasodilation was confirmed to be impaired in insulin-resistant patients, and patients with obesity or insulin resistance have elevated ET-1 concentrations in the blood (32,33). The mechanism underlying the direct vascular effect of insulin on endothelial cells remains controversial.…”

Magnesium deficiency associated with diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis

“…Diabetes duration, poor glycemic control, nephropathy, hypertension, and dyslipidemia were established as modifiable risk factors for DR [5]. Magnesium deficiency is suggested as a possible novel risk factor for DR for the following reasons: i) Mg serves a fundamental role in energy metabolism, ii) retina is the most metabolically active tissue in the body, hence sensitive to hypoxia, iii) Mg has a vital role in the development and physiological eye function in experimental animal studies [7], [8], [18], [34]. The main result of our present meta-analysis provided evidence that hypomagnesemia and low Mg levels in T2DM patients increased the risk of developing DR (OR 4.52 [2.08, 9.81], p=0.0001; MD -0.30 mg/dL [-0.44, -0.15], p<0.0001).…”