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.
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.
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 (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.
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.
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.
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.
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.
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.
Pored odavno prepoznate uloge u metabolizmu kostiju nauĉna javnost sve veću paņnju usmerava ka vanskeletnim efektima vitamina D. Istraņivanja su pokazala da vitamin D deficijencija moņe imati bitnu ...ulogu u glikemijskoj kontroli kod pacijenta sa dijabetesom melitusom tip 2 (DMT2) jer utiĉe na adekvatno luĉenje insulina, pojavu insulinske rezistencije (IR) i sistemske inflamacije. Skoriji dokazi ukazuju na to da vitamin D moņe zańtiti ćeliju od ońtećenja koja su posledica oksidativnog stresa ispoljavajući na taj naĉin i antioksidativni efekat. MeĊutim i pored velikih oĉekivanja interventne studije nisu uspele da taĉno odrede mesto i ulogu vitamina D u kontroli ove hroniĉne bolesti.Ovo istraņivanje je sprovedeno sa ciljem da ispita efekte ńestomeseĉne suplementacije vitaminom D na parametre glikemijske kontrole, oksidativnog stresa i kardiovaskularnog rizika kod pacijenata sa DMT2 koji su na terapiji metforminom.Istraņivanje je sprovedeno kao randomizovana, kontrolisana, prospektivna studija tokom koje je praćeno 130 pacijenata sa DMT2 leĉenih u Domu zdravlja Podgorica, u periodu od 6 meseci (jun-decembar). Regrutovani pacijenti su nasumiĉno podenjeni u 2 grupe (odnos 1:1) pri ĉemu je prva grupa dobijala vitamin D i metformin, dok je druga grupa nastavila da uzima samo metformin. Doziranje je izvrńeno prema smernicama Ameriĉkog endokrinolońkog druńtva u odnosu na poĉetne vrednosti vitamina D u serumu. Svi ispitanici su u 3. i 6. mesecu podvrgnuti kliniĉkom pregledu i detaljnim laboratorijskim analizama. Uticaj na stepen glikemijske kontrole praćen je odreĊivanjem vrednosti glikemije nańte, glikoziliranog hemoglobina (HbA1c), insulinemije nańte kao i odreĊivanjem surogat markera IR (HOMA-IR i TyG indeksa). Uticaj na parametre oksidativnog stresa praćen je odreĊivanjem enzima mijeloperoksidaze (MPO), ksantin oksidaze (XO) i katalaze, zatim odreĊivanjem prisustva nitrata i nitrita (NOx), totalnog oksidativnog (TOC) i totalnog reduktivnog kapaciteta plazme (TRC). TakoĊe su praćeni i produkti oksidativnog ońtećenja lipida odreĊivanjem koncentracije malondialdehida (MDA) i odnosa TG i supstanci koji reaguju sa tiobarbiturnom kiselinom (TG/TBARS). Oksidativno ońtećenje proteina praćeno je odreĊivanjem koncentracije produkata uznapredovale oksidacije proteina (AOPP). Uticaj na parametre kardiovaskularnog rizika praćen je odreĊivanjem vrednosti sistolnog (SKP) i dijastolnog krvnog pritiska (DKP), indeksa telesne mase (BMI), obima struka (OS), TG, ukupnog, HDL i LDL holesterola, kao i aterogenih indeksa Castelli I i Castelli II.Rezultati nańeg istraņivanja su pokazali povoljan efekat vitamina D na vrednosti glikemije nańte nakon 3 meseca, ali ne i nakon 6 meseci. Nakon 6 meseci suplementacije u grupi koja je primala vitamin D vrednosti HbA1c su bile znaĉajno niņe u odnosu na poĉetne, ali statistiĉki znaĉajna razlika izmedju grupa nije zabeleņena. Vitamin D je pokazao povoljan efekat i kada je u pitanju IR merena TYG indeksom nakon 3 i nakon 6 meseci suplementacije dok na vrednosti HOMA-IR indeksa nije bilo znaĉajnog uticaja. U toku perioda praćenja nije bilo statistiĉki znaĉajne razlike izmeĊu grupa u vrednostima produkata oksidativne modifikacije lipida i proteina (MDA i AOPP), mada su pacijenti koji su primali vitamin D imali tendenciju sniņenja vrednosti MDA za razliku od pacijenata koji su primali samo metformin. Nakon 3 meseca zabeleņen je znaĉaj efekat na vrednosti TG/TBARS indeksa u korist pacijenata koji su dobijali vitamin D. Kada je u pitanju efekat na dominantne enzime geneze slobodnih radikala vitamin D je povoljno uticao na vrednosti MPO nakon 3 i nakon 6 meseci suplementacije, dok na vrednosti XO nije ispoljio znaĉajan efekat. Vrednosti parametara antioksidativne zańtite, TOC i NOx se nisu znaĉajno menjale pod uticajem vitamina D u toku perioda praćenja. Većina pacijenata je imala hipertenziju i uzimala je redovno antihipertenzive. Vitamin D nije doveo do znaĉajnog sniņenja SKP i DKP iako je u Metformin + Vitamin D grupi nakon 3. meseca dońlo do statistiĉki znaĉajnog pada vrednosti SKP. Efekat na lipidni status na kraju 3. i 6. meseca je bio povoljan samo kada su u pitanju vrednosti TG, dok na vrednosti ostalih parametara nije bilo povoljnog uticaja. Znaĉajn efekat na aterogene indekse zabeleņen je samo nakon 3. meseca i samo kod Castelli I indeksa. Oralna suplementacija vitaminom D nije imala povoljan efekat na vrednosti BMI i CRP, ali je nakon 3 meseca ispoljila povoljan efekat na vrednosti OS.Kratkoroĉna suplementacija vitaminom D u trajanju od 3 meseca dovodi do znaĉajnog sniņenja vrednosti glikemije nańte, TG/TBARS indeksa i aterogenog indeksa Castelli I kod pacijenata sa DMT2 na terapiji metforminom. Dugoroĉna suplementacija vitaminom D u trajanju od 6 meseci dovodi do znĉajnog sniņenja vrednosti MPO, TG i TYG indeksa, dok povoljan efekat na vrednosti OS predstavlja pre uzgredan nalaz nego odraz povoljnog uticaja vitamina D.
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 (
= 0.015) and compared to the Metformin group (
= 0.001). After 6 months, the xanthine oxidase (XO) activity decreased significantly in the Intervention group compared to the baseline and 3
month levels (
< 0.001). In the Metformin group there was also a significant decrease in XO after 6 months compared to baseline (
< 0.001) and the 3
month (
= 0.003). The catalase activity significantly increased within the Intervention group only when comparing the 3
and 6
month (
= 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.
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