Vitamin D, a crucial hormone in the homeostasis and metabolism of calcium bone, has lately been found to produce effects on other physiological and pathological processes genomically and non-genomically, including the cardiovascular system. While lower baseline vitamin D levels have been correlated with atherogenic blood lipid profiles, 25(OH)D supplementation influences the levels of serum lipids in that it lowers the levels of total cholesterol, triglycerides, and LDL-cholesterol and increases the levels of HDL-cholesterol, all of which are known risk factors for cardiovascular disease. Vitamin D is also involved in the development of atherosclerosis at the site of the blood vessels. Deficiency of this vitamin has been found to increase adhesion molecules or endothelial activation and, at the same time, supplementation is linked to the lowering presence of adhesion surrogates. Vitamin D can also influence the vascular tone by increasing endothelial nitric oxide production, as seen in supplementation studies. Deficiency can lead, at the same time, to oxidative stress and an increase in inflammation as well as the expression of particular immune cells that play a pivotal role in the development of atherosclerosis in the intima of the blood vessels, i.e., monocytes and macrophages. Vitamin D is also involved in atherogenesis through inhibition of vascular smooth muscle cell proliferation. Furthermore, vitamin D deficiency is consistently associated with cardiovascular events, such as myocardial infarction, STEMI, NSTEMI, unstable angina, ischemic stroke, cardiovascular death, and increased mortality after acute stroke. Conversely, vitamin D supplementation does not seem to produce beneficial effects in cohorts with intermediate baseline vitamin D levels.

Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1–Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value 1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism.

The aim of this analysis was to assess the costs associated with the hospitalizations of persons with diabetes in a Romanian public hospital. We performed a retrospective “top-down” cost analysis of all adult patients discharged from a tertiary care hospital with an ICD-10 primary or secondary code of diabetes mellitus (type 1, type 2, or specific forms) between 1 January 2015 and 31 December 2018. All costs were adjusted with the annual inflation rates and converted to EUR. We included 16,868 patients with diabetes and 28,055 episodes of hospitalization. The total adjusted hospitalization cost in the analyzed period was EUR 26,418,126.8 and the adjusted median cost/episode of hospitalization was EUR 596.5. The mean length of a hospital stay/episode was 7.3 days. In the multivariate regression analysis, higher adjusted average costs/episodes of hospitalization and longer lengths of hospital stays were associated with increasing age, the presence of cardiovascular diseases, chronic kidney disease, and foot ulcerations. Moreover, a significant association between the average cost/episode of hospitalization and the length of hospital stay was observed (β = 0.704, p < 0.001). This study shows the burden on Romanian public hospitals of inpatient diabetes care and the main drivers of the costs.