Faculty of Medicine

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BIOMARKERS IN OBESITY-RELATED METABOLIC SYNDROME: FROM PATHOPHYSIOLOGY TO CLINICAL APPLICATION
(Macedonian Association of Anatomists and Morphologists, 2025-11-25)
Kostovska, Irena
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Obesity-related metabolic syndrome (MetS) represents a complex, multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, hypertension, and chronic low-grade inflammation. Its rising global prevalence underscores the urgent need for comprehensive understanding and early detection strategies. While traditional clinical and biochemical parameters provide insight into overt metabolic dysfunction, they often fail to capture upstream molecular disturbances. Recent research has identified a spectrum of novel biomarkers that reflect the pathophysiological mechanisms underlying MetS, including inflammatory mediators (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1), adipokines and hormonal regulators (adiponectin, leptin, resistin, visfatin, ghrelin, glucagonlike peptide-1), oxidative stress and endothelial dysfunction markers (malondialdehyde, 8-isoprostane, oxidized LDL, asymmetric dimethylarginine, paraoxonase-1), thyroid function indicators (TSH, free thyroxine, anti-thyroid peroxidase antibodies), vitamin D, and genetic/epigenetic modulators (microRNAs and DNA methylation patterns). This review summarizes current evidence on these biomarkers, highlighting their roles in elucidating disease mechanisms, enabling early risk assessment, guiding therapeutic interventions, and supporting precision medicine approaches. Future research directions are proposed to standardize assays, validate findings across diverse populations, and develop integrated multi-marker panels to optimize the management of obesity-related MetS.
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ASSOCIATED RISK FACTORS AND PREVALENCE OF METABOLIC SYNDROME IN PEOPLE WHO ARE LIVING WITH HIV AND ARE ON ANTIRETYROVIRAL TREATMENT
(Macedonian Association of Anatomists, 2025-05-02)
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Saveski, Velimir
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The extended life expectancy of people living with HIV infection increases the risk of metabolic syndrome (MS). To assess the prevalence of MS, the association of triple regimen antiretroviral therapy (ART) and the role of the chronic inflammatory process caused by the HIV virus with the onset of MS. A prospective cross-sectional study was conducted on 141 HIV infected adult patients with confirmed HIV infection who regularly receive ART at the University Clinic for infectious diseases and febrile conditions in Skopje. In all patients, the presence of MS was determined according to the criteria of the National Cholesterol Education Program Adult Treatment Panel ATP III (NCEP ATPIII) 2005. The statistical software SPSS (ver. 23.0; IBM, SPSS, USA) was used for statistical analysis. The prevalence of MS in persons with HIV infection in RNM was 17.96%. The group of patients with MS were significantly older and had significantly higher Body Mass Index and greater waist circumference (28.82 ± 4.6 kg/m2 vs 23.91 ± 3.6 kg/m2 p<0.0001) and (101.04 ± 12.4 vs 87.19 ± 9.8cm,p<0.0001), respectively. Treatment of patients with ART did not show a significant difference in the group with and without MS. There is a significant difference regarding the frequency of IL 6 (p=0.012). Aging and increasing Body Mass Index are significant risk factors in the developing of MS in persons with HIV infection who are on ART treatment.
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Insulin resistance and metabolic syndrome in hepatitis C virus seronegative heroin dependents
(Институт за јавно здравје на Република Македонија = Institute of public health of Republic of Macedonia, 2023-12)
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Janicevic Ivanovska, Danijela
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Initial studies on impaired glucose-insulin homeostasis in heroin dependents have not defined the impact of concomitant hepatitis C infection (HCV), which has been strongly associated with the development of insulin resistanceand metabolic syndrome (MS). The aim of our study was to evaluate the association of heroin dependence with glucose-insulin homeostasis and MS in heroin dependents with HCV seronegativity. Materials and methods: The study was prospective and cross-sectional, including 160 heroin dependents compared to a control group of 60 participants.MS was diagnosed using International Diabetes Federation criteria. The homeostatic model assessment for insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-%B) were used for assessing insulin resistance and β-cell function of pancreas. Results: MS was detected in 9.32% of heroin addicts. Heroin dependents with MS compared to dependents without MS were older, had higher BMI, waist circumference and significantly higher systolic and diastolic blood pressure, increased triglycerides (F=8.233, df=2, p<0.001), apoB (F=8.154, df=2, p=0.001), and reduced HDL-C (F=25.926, df=2, p<0.001) and apoA-I (F=16.406, df=2, p<0.001), significantly increased inuslinemia (F=4.928, df=2, p<0.05), insulin resistance-HOMA-IR (F=4,928, df=2, p<0,05) and insignificantly increased pancreatic β-cell function (194.66 ±224.05) (F=2.461, df=2, p>0.05). Conclusions: Insulin resistance and МS, independent of HCV, was also registered in heroin dependence. Timely recognition will enable more successful treatment of comorbidities and illicit drug dependence.
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Effects of Rosiglitazone on Metabolic Parameters and Adiponectin Levels in Fructose-Fed Rats
(Scientific Foundation Spiroski (publications), 2009-03-01)
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Dimitrovski, Chedo
Aim. To investigate the effect of the peroxisome proliferators-activator receptor gamma agonist, rosiglitazone, on metabolic parameters and adiponectin levels in an animal model of the metabolic syndrome. Material and methods. Metabolic syndrome was induced in 32 male Wistar rats by adding a fructose in drinking water for 12 weeks. During the last 4 weeks, 16 rats were treated with rosiglitazone (5 mg/kg/day), while the remaining 16 did not receive any medication (fructose group). Another control group consumed standard rat chow and water for 12 weeks. Results. Chronic fructose administration induced a significant increase in systolic blood pressure (SBP), body weight, serum triglycerides (TG), free fatty acids (FFA), insulin, glucose AUC0-120 (during oral glucose tolerance test) and decreased serum high density lipoprotein (HDL) cholesterol and adiponectin concentrations compared with the control group. Treatment with rosiglitazone over the final 4 weeks reversed these effects and significantly reduced SBP, TG, FFA, insulin concentrations and glucose AUC0-120 compared with the fructose group. In addition, rosiglitazone increased serum levels of adiponectin twofold from 3.44 ± 0.46 to 7.03 ± 1.30 μg/ ml. Conclusion. This study indicates that rosiglitazone treatment improves the components of the metabolic syndrome, which is accompanied with an increase in adiponectin concentrations.
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RELATIONSHIP BETWEEN THE MEATABOLIC SYNDROME AND THE INDIVIDUAL METABOLIC RISCK FACTORS AND SYMPTOMATIC AND ASYMPTOMATIC CAROTID ARTERY DISEASE: IS THE WHOLE LARGER THAN ITS PARTS
(Macedonian Association of Anatomists and Morphologists, 2021)
Deleva Stoshevska, Tatjana
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Nikoloska, Sofija
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Stoshevski, Bojan
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Nikoloski, Marko
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Metabolic syndrome (MetS) is a group of at least three of the following metabolic risk factors : central obesity, elevated glycaemia, high serum triglycerides, low serum high-density lipoprotein (HDL), and high blood pressure. Atherosclerosis is the most common cause of extracranial CAD. It may be asymptomatic and symptomatic with clinical presentation of cerebrovascular insult (CVI) and transient ischemic attack (TIA). Aim: to determine the relationship between MetS as a whole compared to individual metabolic risk factors and CAD. This analytical unicentric cross-sectional study included 160 subjects divided into two groups: 80 subjects with MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria in the examined group (EG) and 80 subjects who have 1 or 2 individual metabolic risk factors and do not meet the diagnostic criteria for MetS in the control group (CG). CAD was diagnosed with the Esaote My Lab70 HVG device, with a linear probe (7.5 MHz), according to the Ultrasound consensus criteria for CAD of the Association of Radiologists (2002, San Francisco). CAD was significantly more frequently diagnosed in 77 (96.25%) EG subjects, compared to 34 (42.5%) CG subjects (p <0.0001). In EG symptomatic CAD had 52 subjects (67.5%) compared to only 2 (5.9%) subjects in CG. With asymptomatic CAD were 25 (32.47%) EG and 32 (94.12%) CG subjects, which was statistically confirmed as significant (p <0.0001). MetS is significantly associated with CAD, which is of cardinal importance for primary and secondary prevention of CVI and TIA.
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ASSOCIATION OF THE NUMBER OF COMPONENTS OF THE MEATBOLIC SYNDROME AND CAROTID ARTERY DISEASE
(Macedonian Association of Anatomists and Morphologists, 2021)
Deleva Stoshevska, Tatjana
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Nikoloska, Sofija
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Nikoloski, Marko
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Stoshevski, Bojan
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Metabolic syndrome (MetS) is a group of at least three of the following metabolic disorders: central obesity, elevated glycaemia, high serum triglycerides, low serum high-density lipoprotein (HDL), and high blood pressure. Carotid artery disease (CAD) involves changes in the arterial wall that cause thickening of the intima-media (IMT), narrowing, or complete obstruction of the carotid artery lumen. Objective:To determine the impact of the number of MetS components on CAD. This analytical unicenteric cross-sectional study included 80 subjects with MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. CAD was diagnosed with the Esaote My Lab70 HVG device, with a linear probe (7.5 MHz), according to the Ultrasound consensus criteria for CAD of the Association of Radiologists (2002, San Francisco). 34 subjects (42.5%) had 4 components of MetS, 24 subjects (30%) had 3 components, 22 subjects (27.5%) had 5 components. Gender and age have no statistically significant effect on the influence of metabolic risk factor as components of MetS (p = 0.38, p = 0.72, respectively). CAD was diagnosed in 77 subjects (96.25%), in 21 subject (87.5%) with 3 components of MetS and in all subjects with 4 and 5 components of MetS.This statistically confirmed that subjects with a smaller number of MetS components significantly have less CAD (p = 0.026). The increase in the number of components and the synergistic effect of individual MetS components is significantly associated with CAD.
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Metabolic syndrome in perimenopausal patients with fractional explorative curettage
(2022)
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Georgiev, Dimitar
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METABOLIC SYNDROME (METS) AS ONE OF THE MAJOR COMORBIDITIES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
(Association of pulmologists from Republika Srpska, 2023-05)
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Baloski, Marjan
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Bushev, Jane
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Mickovski, Ivana
Aim: We aimed to investigate the association between COPD and MetS, the relation to the severity of airflow limitation. Methods: This is a cross-sectional study including 220 patients with initially diagnosed COPD (IG), aged 40 to 75 years and 58 non-COPD subjects matched by age, smoking status, body mass index, as controls (CG). All study participants underwent anthropometric measurements, fasting blood sugar (FBS), lipid profile, pulmonary evaluation (dyspnea severity assessment, baseline and postbronchodilator spirometry, gas analyses, chest X-ray). Results: Results presented statistically significant difference in presence of MetS in COPD patients compared to controls (32.27% vs 10.34%; P=0.0009). According to the GOLD classification, the frequencies of MetS in COPD patients were categorized in stages I, II, III, IV (17.54%, 37.10%, 34.62%, 40.82%, respectively). The proportion of patients with increased glycemic values was: a) GOLD1 - 18 (31.58%); b) GOLD 2 - 32 (51.61%); c) GOLD3 - 29 (55.77%); and d) GOLD4 - 31 (63.27%). There was no significant difference between IG and CG patients regarding HDL level. According to arterial hypertension the highest proportion was observed in GOLD3 - 22 (42.31%) followed by GOLD4 - 20 (40.82%), and GOLD3 - 22 (35.48 %), smallest in GOLD1 - 17 (29.82%). Conclusion: We found higher prevalence of MetS in patients with COPD even in early COPD stages compared to non-COPD. Our findings suggest an urgent need to develop comprehensive strategies for prevention, screening and start of treatment in early stage.
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Chronic Obstructive Pulmonary Disease (COPD) as a risk factor for Metabolic Syndrome (MetS)
(Slovenian Respiratory Society, 2020-12)
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Trajkovska, Ivana
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Buklioska, Adriana
Background: MetS represents a cluster of risk factors (abdominal obesity, atherogenic dyslipidemia, hypertension and insulin resistance) that predispose affected patients to systemic inflammation, cardiovascular disease and physical inactivity. COPD is a major health problem worldwide, the fourth leading cause of death with prevalence in increase. There is a limited data about the prevalence of MetS in COPD. The aim of the study is to determine the frequency of coexisting MetS in COPD. Methods: Case control study of 120 patients with COPD (82 men and 38 women, aged 40-75 years, mean age 64.2±10.4), diagnosed according to Global Initiative for Chronic Obstructive Lung Disease, 30 healthy non-COPD subjects, randomly selected as controls. Anthropometric measurements, fasting blood sugar (FBS), lipid profile, high-sensitivity C-reactive protein (hsCRP), spirometry, CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires, were assessed. COPD subjects were stratified based on combined assessment test (ABCD criteria) and spirometry (stages I - IV). Results: The presence of MetS was diagnosed in 50(41.67%) of COPD patients vs. 5(16.67%) of controls (p=0.01). The frequencies of the MetS in patients with COPD, GOLD stages I, II, III, and IV, were 50(41,67%), 66(55%), 60(50%), 42(35%) respectively. Frequency of MetS according to combined assessment test (A, B, C, D) was 42(35%), 54(45%), 25(30%), 36(30%) respectively. The presence of MetS was associated with significantly worse cough, sleep and mood (p<0.01) and higher total CAT score (p=0.031). Average BMI was 29.18. There was a correlation between the presence of MetS and hs-CRP (p=0.02) and no correlation with the pulmonary function. FBS was higher in COPD than controls (8.5±1.2mmol/L vs 5.4±1.1mmol/L) with statistical significance (p<0.0001), but HDL was lower in COPD than controls (42.1±5.4mg/dl vs 53±3.6mg/dl) with statistical significance (p<0.0001). Waist circumference and blood pressure were higher in COPD than controls 93.8s±2.4m vs. 92.3±3.1sm, p=0.004, and mean systolic BP 135±10mmHg vs. 113.5±8.1mmHg, p < 0.0001. Conclusion: The high prevalence of MetS in patients with COPD show the urgent need to develop comprehensive strategies for prevention, screening and start of treatment in early stage. Correction of the MetS may have a significant role in prevention of complications related with the COPD.
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Metabolic Syndrome (MetS) as a comorbidity of Chronic Obstructive Pulmonary Disease (COPD)
(European Respiratory Society, 2021-09-05)
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Mickovski, Ivana
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Kamchevska, Nade Kochovska
We aimed to investigate the association between COPD and MetS, the relation to the severity of airflow limitation and the level of serum C-reactive protein (CRP). Cross-sectional study including 120 patients with initially diagnosed COPD, aged 40-75 years and 60 non-COPD controls, matched by age, smoking status, body mass index. All study participants underwent anthropometric measurements, fasting blood sugar (FBS), lipid profile, CRP, pulmonary evaluation (dyspnea severity assessment, baseline and post-bronchodilator spirometry, gas analyses, chest X-ray). Results presented statistically significant difference in presence of MetS in COPD patients compared to controls (47.5% vs 20.0%, p=0.0004). According to the GOLD classification, the frequencies of MetS in COPD patients were categorized in stages I, II, III, IV (40.0%, 45.8%, 46.7%, 43.0% respectively), and according to combined assessment test in A, B, C, D (29.2%, 37.5%, 35.0%, 41.7% respectively). COPD patients with MetS presented significant association with CRP (p=0.001) and no association with pulmonary function. FBS was higher in COPD compared to controls (8.4±1.1mmol/L vs. 4.9±2.1mmol/L, p<0.0001), but HDL was lower in COPD than non-COPD (39.1±6.4mg/dl vs 49.6±3.9mg/dl, p<0.0001). Waist circumference and blood pressure (BP) were higher in COPD 95.8±3.4cm vs. control group 91.8±2.9cm, p<0.0001. Mean systolic BP was 138.3±12.2mmHg vs. 125.5±6.1mmHg, p<0.0001 in non-COPD. We found higher prevalence of MetS in patients with COPD even in early COPD stages compared to non-COPD group. Our findings suggest an urgent need to develop comprehensive strategies for prevention, screening and start of treatment in the early stage of the disease.

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