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Summary Background FTO, a gene recently discovered in genomewide associated studies for type 2 diabetes mellitus (T2D), play an important role in the management of energy homeostasis, nucleic acid demethylation and regulation of body fat mass by lipolysis. The aim of this study was to analyze the association of FTO rs8050136 A>C genetic variant with clinical and biochemical parameters of T2D in the population of West Balkan region (Bosnians and Herzegovinians and Kosovars). Methods The study included 638 patients with T2D and prediabetes and 360 healthy controls of both genders, aged from 40 to 65 years. Patients were recruited at the Clinical Centre University of Sarajevo, University Hospital of Clinical Centre in Banja Luka, General Hospital in Tešanj and Health Centre in Prizren. Genotyping of analyzed FTO polymorphism rs8050136 A>C was performed by qPCR allelic discrimination. Results Genotype frequencies of the analyzed polymorphism were comparable between patients with T2D, prediabetic patients, and healthy population. Logistic regression analyses didn’t show significant association of FTO rs8050136 A allele with increased risk of T2D. However, risk A allele was significantly associated with higher levels of HbA1c, insulin, HOMA-IR index, diastolic blood pressure, and inflammatory markers (fibrinogen and leukocytes) as well as showed tendency of association with increased values of obesity markers (BMI, waist and hip circumference). Conclusions Results of our study showed a significant association of FTO genetic variant rs8050136 A>C with the major markers of insulin resistance, obesity and inflammation, opening new avenues for solving many unclear questions in the pathogenesis of T2D.

Lejla Mahmutović, T. Bego, M. Sterner, Gabriella Gremsperger, E. Ahlqvist, Zelija Velija Asimi, B. Prnjavorac, N. Hamad et al.

Abstract Background Previous studies reported conflicting results regarding association of insulin receptor substrate 1 (IRS1) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Methods Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Results Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], padd = 0.025; B = 0.079, 95% CI [0.006, 0.150], padd = 0.033, respectively) in T2D, and with HbA1c (B = 0.034, 95% CI [0.003, 0.065], pdom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = −0.17, 95% CI [−0.03, −0.002], padd = 0.030) and HbA1c (B = 0.03, 95% CI [0.002, 0.06], pdom = 0.040) in non-drug-treated T2D. Conclusions We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA1c levels in Bosnia and Herzegovina’s population.

Una Suljić, B. Prnjavorac, T. Bego, M. Malenica, T. Dujic, I. Prnjavorac, A. Causevic, L. Šaranović

Aim To investigate whether or not additional treatment of ischemic heart disease with trimetazidine could improve effort tolerance and overall quality of life of patients with ischemic heart disease. Methods The study included 200 patients with ischemic heart disease. The sample was divided into 2 randomly selected groups: experimental and control group. The diagnostic procedures included: trade-mill test according to Bruce protocol, heart ultrasound for assessment of ejection fraction, test for the assessment of quality of life and subjective problems (Short Form SF 36). Patients were tested for time of discharge from hospital, after 6 and 12 months, including re-evaluation of the overall condition of the previous period. Results Patients have been tested for the tolerance of effort with the measurement Metabolic Equivalent of TASK (METs), which is the equivalent of physical labor. Patients treated with trimetazidine since the time of hospital discharge achieved an average of 3.68, after 6 months 5.68, and after 12 months 7.79 METs. The control group achieved 3.68, 3.59 and 3.87 METs, respectively. Using Mann-Whitney test no difference at discharge time (p=0.880), but after six and twelve months there was some difference (p<0.001). Results of ejection fraction measured by echocardiography were similar. No difference between the two groups with regard to time of discharge (p=0.821, but p<0.001 after six and twelve months, respectively). Conclusion Patients treated with conventional therapy including trimetazidine have better tolerance to effort and better ejection fraction on heart ultrasound examination in comparison with those treated without trimetazidine, so trimetazidin improve the metabolic balance of heart muscle.

Aim To analyse the long-term impact of altered metabolism on the level of mediators of inflammatory response in female patients with type 2 diabetes. Methods This study included 97 female patients with type 2 diabetes and 107 female, nondiabetic control subjects, who were recruited at the Clinical Centre University of Sarajevo and the General Hospital Tešanj. The effects of glycaemic control on markers of inflammatory response represented by C-reactive protein (CRP), fibrinogen, leukocytes, sedimentation rate, and cytokine IL-6 were tested. All subjects were free of evidence of infections, surgery, thyroid disease, polycystic ovarian syndrome, active liver and kidney damage. All biochemical analyses were performed according to standard International Federation of Clinical Chemistry (IFCC) protocols. Results A significant increase of fibrinogen (p<0.001), CRP (p=0.001), interleukin-6 (p=0.013), leukocytes (p<0.001) and sedimentation rate (p=0.008) in diabetic female population compared to control subjects was found. A significant correlation between CRP and haemoglobin A1c (p=0.035), interleukin-6 and glucose (p=0.032), IL-6 and body mass index (p=0.007) was found. Conclusion Our data suggest that inflammation plays an important role in the pathogenesis of diabetes in female diabetic population. A more detailed study on a far larger number of subjects is needed if they were to be used effectively as biomarkers in the primary prevention of type 2 diabetes in this population.

Objective: Tobacco cigarette smoking is one of the major leading causes of death throughout the world. Smoking has both acute and chronic effect on haematological parameters. The aim of the present study was to assess the extent of adverse effects of cigarette smoking on biochemical characteristics in healthy smokers. Subjects and Method: One hundred and fifty six subjects participated in this study, 56 smokers and 100 non-smokers. The smokers were regularly consuming 10-20 cigarettes per day for at least 3 years. Complete blood cell count was analyzed by CELL-DYN 3700 fully automatic haematological analyzer. Results: The smokers had significantly higher levels of white blood cell (p<0,001), hemoglobin (p=0,042), mean corpuscular volume (p=0,001) and mean corpuscular hemoglobin concentration (p<0,001). All other measured parameters did not differ significantly. Cigarette smoking caused a significant increase (p<0,001) in red blood cells, white blood cells (p=0,040), hemoglobin (p<0,001), hematocrit (p=0,047) and mean corpuscular hemoglobin (p<0,001) in males in comparison to female smokers. Conclusion: In conclusion, our study showed that continuous cigarette smoking has severe adverse effects on haematological parameters (e.g., hemoglobin, white blood cells count, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cells count, hematocrit) and these alterations might be associated with a greater risk for developing atherosclerosis, polycythemia vera, chronic obstructive pulmonary disease and/or cardiovascular diseases.

H. Divanović, D. Mulić, Asima Padalo, Edita Rastoder, Šejla Pedljak, Nermina Žiga, T. Bego

B. Prnjavorac, R. Sejdinović, E. Jusufović, J. Mehić, Omer Bedak, Jasmin A Fejzic, Nedžada Irejiz, M. Malenica et al.

Background: Acute respiratory distress syndrome (ARDS) is life treating condition, with intensive general inflammation. Objective: Inflammation can be present with infection or without. Septic embolism, according to our previous experience, is more often multiple, than single. General hypoxia of hall body cause damage of all tissue, and generalinflammationintensifies. A vicious circle was formed and inflammation runs its course in what is very often irrelevant how it was begun.How often pulmonary embolism causes ARDS and what are the main features of this disease, is the goal of the study. Methods: Patients with ARDS, treated in pulmonary intensive care unit were analyzed. Chest X-ray, microbiological analysis of sputum or bronchoalveolar lavage specimen, chest CT scan, blood culture, CRP (mg/dl), deep-dimmer and blood cell count, were performed for all cases. Results: In three years period 53 patients with ARDS were treated. Out of all 19 with septic pulmonary embolism (14 multiple), (CRP 198±28). In only 12 patients origin of venous thrombus was found. Out of all 6 patients have massive non septic embolism (CRP 28±7), 18 heavy pneumonia (CRP 166±28), 4 with interstitial pneumonia (CRP 76±19), 5 with massive TB with caverns (CRP 35±13) and 6 with not well defined cause. Blood culture was positive in 14 cases with septic embolism and in 11 cases with pneumonia. CRP was elevated in all cases but highest was in septic embolism (Mann-Whitney test p=0,024). Conclusion: Septic pulmonary embolism was common cause of ARDS, mostly as multiple, and should be considered even if origin of thrombus was found or not.

Barbara Ostanek, S. M. Bedrac, B. Kern, P. Vrtačnik, V. Mlakar, T. Bego, R. Komadina, R. Trebše et al.

Introduction: Because of increasing prevalence of T2MD worldwide, it’s very important to recognize risk factors for diabetic complications, as soon as possible. Symptoms of complications appear a few or many years after tissue damage. So, it’s imperative to establish surveillance of diabetics with laboratory and other diagnostic procedures for early recognition of diabetic complications. Follow up of clinical curs of diabetes, by using databases of patients, provide possibility for permanent analysis of important laboratory parameters and any changes could be registered. Although an emerging evidence suggests a strong association of ALT (alanine aminotransferase) and γGT (gamma glutamyl transferase) activity with type 2 diabetes mellitus (T2DM), only a limited number of studies have analyzed the association of AST (aspartate aminotransferase), ALT, γGT, and ALP (alkaline phosphatase) activities in controlled T2DM. Material and Methods: Gender differences are of special interest in trying to follow diabetes progression and development of its complications. Here the activities of ALT, AST, γGT, ALP were analyzed as well as levels of glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in 40 T2DM patients and 40 age-matched healthy subjects. Blood samples were collected from all participants in regular 3-months intervals up to 6 months period. Standard IFCC enzyme protocols were used to determine enzyme activities. Results and discussion: In first measured interval, significantly higher activities of ALT (p= 0,050) and glucose levels (p=0,045) were shown in male. A significant correlation was shown between ALT and AST activity with FPG and HbA1c levels in first and third measured interval. ALT activity was much higher in the group of patients with poor glycemia control. Average levels of activities of enzymes stay nearly in normal limits, but changes of enzymes activities should be recognized as soon as possible, earlier than tissue changes and diabetic complications become irreversible.

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