Cluster analysis of patient characteristics, treatment modalities, renal impairments, and inflammatory markers in diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is caused by an interplay of various factors where chronic hyperglycemia and inflammation have central role in its onset and progression. Identifying patient groups with increased inflammation in order to provide more personalized approach has become crucial. We hypothesized that grouping patients into clusters according to their clinical characteristics could identify distinct unique profiles that were previously invisible to the clinical eye. A cross-sectional record-based study was performed at the Primary Health Care Center Podgorica, Montenegro, on 424 T2DM patients aged between 30 and 85. Using hierarchical clustering patients were grouped into four distinct clusters based on 12 clinical variables, including glycemic and other relevant metabolic indicators. Inflammation was assessed through neutrophil-to-lymphocyte (NLR) and platelet to lymphocyte ratio (PLR). Cluster 3 which featured the oldest patients with the longest T2DM duration, highest hypertension rate, poor glycemic control and significant GFR impairment had the highest levels of inflammatory markers. Cluster 4 which featured the youngest patients, with the best glycemic control, the highest GFR had the lowest prevalence of coronary disease, but not the lowest levels of inflammatory markers. Identifying these clusters offers physicians opportunity for more personalized T2DM management, potentially mitigating its associated complications.

Multimarker Approach as More Reliable Method Than Single Vitamin D in Relationship with Type 2 Diabetes Mellitus in Montenegrin Postmenopausal Women.

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.

The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study.

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.

Data-Driven Cluster Analysis of Oxidative Stress Indexes in relation to Vitamin D Level, Age, and Metabolic Control in Patients with Type 2 Diabetes on Metformin Therapy.

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 (57.84 ± 11.46 nmol/L) and cluster 4 (53.78 ± 22.36 nmol/L), falling within the insufficiency range. Cluster 2 had the highest mean level of 25 (OH) D (84.55 ± 22.66 nmol/L), indicative of vitamin D sufficiency. Cluster 3 had a mean vitamin D level below 50 nmol/L (49.27 ± 16.95), 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.

A novel mechanism of vitamin D anti-inflammatory/antioxidative potential in type 2 diabetic patients on metformin therapy.

INTRODUCTION: 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). MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Specialty Training in Family Medicine in Montenegro - an Evaluation of The Programme By the First Generation of Trainees.

INTRODUCTION: One of the aims of health care reform in Montenegro is to strengthen primary care. An important step forward is the implementation of specialty training in family medicine (FM). The aim of this article is to evaluate the implementation of specialty training in family medicine in Montenegro, regarding the content, structure and methods, by the first generation of trainees and the coordinator of the training. METHODS: A questionnaire was sent by mail in July and August 2017 to all 26 eligible trainees who started specialty training in 2013. Twenty-two of the 26 trainees (84.6%) responded. The questionnaire consisted of closed and open-ended questions related to the evaluation of the training. A descriptive quantitative and qualitative analysis with predefined themes and a semi-structured interview with the coordinator were carried out. RESULTS: The process of training in FM was assessed positively by both trainees and the coordinator. The positive assessment included that the specialisation course offered modern design through modules and practice, and trainees both improved their existing knowledge and skills and acquired new ones necessary for everyday work. The coordinator emphasised the importance of the introduction of new teaching methods and formative assessment, the important role of mentors, and the involvement of Slovenian colleagues in the teaching process and supervision of the programme. CONCLUSIONS: The implementation of speciality training in FM in Montenegro was successful. Several assessment methods were used that can be further developed in individual structured feedback, which could stimulate the continual improvement of trainees' knowledge and competencies.

Comparative Analysis of Family Medicine Education and Exams at Cathedras of Family Medicine of Universities in Southeastern Europe - "Splitska inicijativa", Sarajevo, 2017.

Education means: learning, teaching or the process of acquiring skills or behavior modification through various exercises. Traditionally, medical education meant the oral, practical and more passive transferring of knowledge and skills from the educators to students and health professionals. Today the importance of focus on educational quality, particularly in the professions operating in the services required by people is agreed by all involved. The higher educational system shoulders some critical responsibilities in the economic, social, cultural and educational development and growth in the communities. In countries that are in transition it is in charge of educating professional human workforce in every field and if the education is optimal in terms of quality, it is capable of carrying out its responsibilities. It is reason why there is the necessity behind discovering some strategies to uplift the quality of education, especially at university level.. By increasing the courses and establishing universities and higher education centers, the countries around the world have generated more opportunities for learning, especially using modern information technologies. Regarding to evaluating different educational services quality, one of the most important measures should be the way to develop programs to promote quality and also due to the shortage of resources, evaluating the services quality enables the management to allocate the limited financial resources for realization whole educational process. Advances in medicine in recent decades are in significant correlation with the advances in the new models and concepts of medical education supported by information technologies. Modern information technologies have enabled faster, more reliable and comprehensive data collection. These technologies have started to create a large number of irrelevant information, which represents a limiting factor and a real growing gap, between the medical knowledge on one hand, and the ability of students and physicians to follow its growth on the other. Furthermore, in our environment, the term technology is generally reserved for its technical component. This terminology essentially means not only the purchase of the computer and related equipment, but also the technological foresight and technological progress, which are defined as specific combination of fundamental scientific, research and development work that gives a concrete result. The quality of the teaching-learning process at the universities in former Yugoslav countries and abroad, depends mainly of infrastructure that includes an optimal teaching space, personnel and equipment, in accordance with existing standards and norms at the cantonal or entity level, which are required to implement adequately the educational curriculum for students from first to sixth year by Bologna studying concept. For all of this it is necessary to ensure adequate funding. Technologies (medical and information, including communications) have a special role and value in ensuring the quality of medical education at universities and their organizational units (faculties). "Splitska inicijativa" project, which started 6 years ago as simple intention to exchange experiences of application new model of education, based on: Bologna studying concept, and other types of under and postgraduate education, was good idea to improve also theory and practice of it within Family medicine as academic and scientific discipline. This year scope of our scientific meeting held in Sarajevo on 24th and 25th March 2017, was quality assessment of theoretical and practical education and, also, evaluation of knowledge by students exams (a-y).

Subclinical Hypothyroidism - Whether and When To Start Treatment?

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.