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.

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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.

1Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina 2Clinics for Endocrinology, Diabetes and Metabolism Diseases, University Clinical Centre of Sarajevo, Sarajevo, Bosnia and Herzegovina 3General Hospital of Tesanj, Tesanj, Bosnia and Herzegovina 4Department of Pathophysiology, Faculty of Pharmacy; University Sarajevo, Sarajevo, Bosnia and Herzegovina 5The Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia 6Institute for Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic 7Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina

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.

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.

Aims Metformin is the most widely used oral anti-diabetes agent and has considerable benefits over other therapies, yet 20–30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter-individual variability is unclear. We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes. Methods This prospective observational cohort study included 92 patients with newly diagnosed Type 2 diabetes, incident users of metformin. Patients were genotyped for two common loss-of-function variants in the OCT1 gene (SLC22A1): R61C (rs12208357) and M420del (rs72552763). The association of OCT1 reduced-function alleles with gastrointestinal side effects was analysed using logistic regression. Results Forty-three patients (47%) experienced gastrointestinal adverse effects in the first 6 months of metformin treatment. Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07–5.01, P = 0.034). Conclusions In conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects. These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. These data could contribute to more personalized and safer metformin treatment. Diabet. Med. 33, 511–514 (2016)

Metformin is the most widely used oral anti‐diabetes agent and has considerable benefits over other therapies, yet 20–30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter‐individual variability is unclear. We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced‐function polymorphisms with common metformin‐induced gastrointestinal side effects in Type 2 diabetes.

To investigate association of two LPIN1 gene variations with main traits of metabolic syndrome (MS) (waist circumference, body mass index, blood pressure, triglycerides, HDL-cholesterol and fasting glucose levels) in population from Bosnia and Herzegovina.