Is Vitamin D Deficiency Related to Accumulation of Advanced Glycation End Products, Markers of Inflammation, and Oxidative Stress in Diabetic Subjects?

Abstract

Objectives. In diabetes accumulated advanced glycation end products (AGEs) are involved in the striking cardiovascular morbidity/mortality. We asked whether a hypovitaminosis D associates with an increased formation and toxicity of AGEs in diabetes. Methods. In 276 diabetics (160 M/116 F, age: 65.0 ± 13.4; 43 type 1,T1DM, and 233 type 2 patients, T2DM) and 121 nondiabetic controls (60 M/61 F; age: 58.6 ± 15.5 years) routine biochemistry, levels of 25-hydroxyvitamin D3 (25-(OH)D), skin autofluorescence (SAF), plasma AGE-associated fluorescence (AGE-FL), Nε-(carboxymethyl)lysine (CML), soluble receptor for AGEs (sRAGE), soluble vascular adhesion protein-1 (sVAP-1), high sensitive C-reactive protein (hs-CRP), and renal function (eGFR) were determined. Results. In the diabetics SAF and AGE-Fl were higher than those of the controls and correlated with age, duration of diabetes, and degree of renal impairment. In T2DM patients but not in T1DM the age-dependent rise of SAF directly correlated with hs-CRP and sVAP-1. 25-(OH)D levels in diabetics and nondiabetics were lowered to a similar degree averaging 22.5 ng/mL. No relationship between 25-(OH)D and studied markers except for sVAP-1 was observed in the diabetics. Conclusion. In diabetics hypovitaminosis D does not augment accumulation of AGEs and studied markers of microinflammation and oxidative stress except for sVAP-1.

Correlation between follicular fluid levels of sRAGE and vitamin D in women with PCOS

“…The role of vitamin D has been defined as a vascular protective agent that is mediated by counteracting the deleterious actions of AGEs on the endothelial cells (by inhibiting NF-κB pathway that is activated by AGEs) [37]. On the other hand, one study found no link between vitamin D and AGEs in diabetic patients [43]. Accumulating evidence has suggested that vit D3 replacement improves the clinical and metabolic outcomes in women with PCOS [26,27,44].…”

Effect of vitamin D supplementation versus placebo on essential hypertension in patients with vitamin D deficiency: a double‐blind randomized clinical trial

“…Third, vitamin D deficiency leads to vascular endothelial dysfunction. Studies have shown that 1,25 dihydroxy vitamin D [1,25(OH)2 D] reduces the deleterious effects of advanced glycation end product on the endothelium 34,35 . Furthermore, vitamin D improves the activity of the nitric acid system and reduces inflammatory and atherosclerotic factors, and its deficiency is a risk factor for hypertension 36 .…”

Serum 25-hydroxyvitamin D3 is associated with advanced glycation end products (AGEs) measured as skin autofluorescence: The Rotterdam Study

“…A few earlier cross-sectional studies on the relationship between 25(OH)D 3 and SAF in smaller study populations showed inconsistent results. In 276 patients with type 1 and type 2 diabetes and 121 non-diabetic controls no association was observed [ 20 ]. Another cross-sectional study in 119 healthy participants and 27 hypertensive patients also reported no association [ 37 ].…”

“…Secondly, existing human studies were small-scaled, cross-sectional, limited to special patient groups, and conclusions were contradictory. In a study of 276 type 1 and type 2 diabetics and 121 non-diabetic controls, no association was observed between 25(OH)D 3 and SAF [ 20 ]. In contrast, a significant inverse relationship between 25(OH)D 3 and AGEs measured by skin autofluorescence (SAF) was observed in a recent study of 245 type 2 diabetes patients treated with lifestyle advice, metformin and/or sulphonylurea-derivatives [ 21 ].…”