Vitamin D deficiency could play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) as it may alter several crucial processes in the development of diabetes and its complications, such as pancreatic insulin secretion, peripheral insulin resistance, persistence of systemic „sterile” inflammation and immune activation. Vitamin D may also have an antioxidant effect through the inhibition of free radicals generation. The reported study was designed with eligible consecutively recruited patients with T2DM on standard metformin therapy (n=130), randomized in 1:1 ratio, considered to have undergone Vitamin D supplementation according to the guidelines proposed by the Endocrine Society, or to have continued with metformin only. The potential benefit was monitored through the influence on glycemia level, glycated haemoglobin (HbA1c), insulin resistance index (calculated as homeostatic model assessment; HOMA-IR), Castelli Risk Index I and Tryglicerides/Thiobarbituric acid-reactive substances (TG/TBARS) Index in a 6-month follow up period. Our study indicates that oral daily doses of vitamin D improve HbA1c levels over the 3-month and 6-month period, followed by a significant decrease in advanced oxidation protein products levels over the 3-month period when higher vitamin D doses are given. The effect of vitamin D on HOMA-IR index, malondialdehyde levels and TG/TBARS index was not statistically significant. Further investigation should consider defining the doses of vitamin D in patients with T2DM which may attenuate the oxidative stress risk, the risk of metabolic syndrome and the risk of related cardiovascular events.

The performed study focused on determining the effect of vitamin D supplementation on enzymes involved in both inflammation and reactive oxygen species (ROS) production and ROS degradation in patients with type 2 diabetes mellitus (T2DM). The 6-month follow-up, randomized, controlled study included 140 patients with T2DM, ≥ 30 years old, with good metabolic control, treated with metformin and lifestyle advice only. All patients were randomly assigned to two groups (70 each). Patients from the first group (Intervention group) were assigned to receive vitamin D3 50 000 IU or 14 000 IU regarding their vitamin D baseline levels. Patients from the second (Metformin) group continued to receive only metformin during the 6-month study period. After 6 months, the myeloperoxidase activity was significantly lower and gradually decreased in the Intervention group by about 40%, compared to the baseline measurement (p = 0.015) and compared to the Metformin group (p = 0.001). After 6 months, the xanthine oxidase (XO) activity decreased significantly in the Intervention group compared to the baseline and 3rd month levels (p < 0.001). In the Metformin group there was also a significant decrease in XO after 6 months compared to baseline (p < 0.001) and the 3rd month (p = 0.003). The catalase activity significantly increased within the Intervention group only when comparing the 3rd and 6th month (p = 0.027). Our study showed that vitamin D may improve endothelial dysfunction in patients with T2DM on metformin therapy by influencing two important factors implicated in the pathogenesis of diabetic complications – ROS production and inflammation, which can additionally contribute to a stable metabolic control during metformin therapy.

Subclinical hypothyroidism represents a state with increased values of thyroid stimulating hormone (TSH) and normal values of thyroxine (T4) and triiodothyronine (T3). The disorder is asymptomatic, and the diagnosis is made based on the results of laboratory findings when the level of TSH reaches values above 4.0 mU/l. It is still subject to debate whether patients with subclinical hypothyroidism are at increased risk of cardiovascular disease, neuropsychiatric and neuromuscular disorders. Studies have shown that the appearance of general symptoms and complications are more common in patients whose values of TSH are above 10 mU/l. Therefore, the initiation of therapy with levothyroxine, which is the foundation of substitution therapy, is advised in patients whose TSH is >10 mU/l. As for patients whose values of TSH are from 4.0 to 10.0 mU/l and who make up 90% of the patients with subclinical hypothyroidism, further research is needed to determine the effects of the disorder and levothyroxine therapy on the health. Until then, the introduction of the substitution therapy in patients with TSH which is <10 mU/l should be considered in the case of the presence of general symptoms, anti-thyroid antibodies, increased lipids and other risk factors, goitre, pregnancy, ovarian dysfunction and infertility.

Recent advances in vitamin D research indicate that patients with type 2 diabetes mellitus (T2DM) are suffering from vitamin D deficiency and increased oxidative stress to a variable extent, which could produce different health impacts for each individual. The novel multivariate statistical method applied in the present study allows metabolic phenotyping of T2DM individuals based on vitamin D status, metabolic control, and oxidative stress status in order to identify effectively different subtypes in our type 2 DM study population. Data-driven statistical cluster analysis was performed with 95 patients with T2DM, treated with metformin. Clusters were based on 12 variables—age, disease duration, vitamin D level, insulin, fasting glycemia (FG), glycated hemoglobin (HbA1c), high-density and low-density lipoprotein, total cholesterol (TC), triglycerides (TG), body mass index (BMI), and triglycerides/glucose index (TYG). The analysis revealed four unique clusters which differed significantly in terms of vitamin D status, with a mean 25 (OH) D level in cluster 1 ( nmol/L) and cluster 4 ( nmol/L), falling within the insufficiency range. Cluster 2 had the highest mean level of 25 (OH) D ( nmol/L), indicative of vitamin D sufficiency. Cluster 3 had a mean vitamin D level below 50 nmol/L ( ), which is considered deficient. Patients in the vitamin D sufficient cluster had a significantly better glycemic and metabolic control as well as a lower level of lipid peroxidation compared to other clusters. The patients from the vitamin D sufficient cluster also had a significantly higher level of vitamin D/MPO, vitamin D/XO, vitamin D/MDA, vitamin D/CAT, and vitamin D/TRC than that in the vitamin deficient and insufficient clusters. The vitamin D deficient cluster included significantly younger patients and had a significantly lower level of AOPP/TRC and albumin/TRC than the vitamin D sufficient cluster. The evidence from our cluster analysis in the context of separated T2DM demonstrates beneficial effects of optimal vitamin D status on metabolic control and oxidative stress in T2DM patients. Older T2DM patients require higher vitamin D levels in order to achieve good metabolic control and favorable antioxidant protection. Since protein damage is more pronounced in these patients, adding water-soluble antioxidant in addition to higher doses of vitamin D should be considered.

Objective: Previous studies suggested that ethnic differences, sex and obesity could modify the relationship between 25-hydroxyvitamin D [25(OH)D], glycometabolic markers and/or type 2 diabetes mellitus (T2D). We aimed to examine the potential relationship between [25(OH)D] and T2D in postmenopausal women in Montenegro. In addition, we aimed to explore if a set of biomarkers, rather than [25(OH)D] as a single biomarker, could better explain its potential association with T2D. Patients and Methods: A total of 116 postmenopausal, otherwise healthy women and 48 postmenopausal women with T2D were included. Univariable and multivariable binary logistic regression analysis, along with principal component analysis (PCA), were applied to test the associations between examined biomarkers/set of biomarkers with T2D. Results: Women with T2D had lower serum [25(OH)D] levels than healthy controls (p = 0.024). No independent relationship between [25(OH)D] and T2D was found. PCA extracted three significant factors that were associated with T2D, i.e., age-glycometabolic-related factor (i.e., with positive loadings of age, glucose and insulin; OR = 11.321, p < 0.001), obesity-inflammation- related factor (i.e., with positive loadings of hsCRP and WC, and negative loading of [25(OH)D]; (OR = 2.079, p < 0.001)) and lipid-related factor (i.e., with positive loadings of TG and LDL-c, and negative loading of HDL-c; OR = 1.423, p = 0.044). Conclusions: The relationship between [25(OH)D] and T2D is modulated by central obesity (as measured by WC) and inflammation (as measured with hsCRP) in postmenopausal women. Their joint measurement, rather than [25(OH)D] itself, could provide better information for the risk assessment for T2D in postmenopausal women.