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.

Summary Background: Peroxisome proliferator-activated receptor gamma (PPARg) is a key transcription factor in adipogene-sis, and also regulates a number of genes associated with lipid storage and insulin sensitivity. Single nucleotide polymorphisms (SNPs) in the PPARG gene have been associated with obesity and diabetes. In this study, we explored the relationship of three PPARG gene variants with the metabolic syndrome (MetS) and related traits in a population from Bosnia and Herzegovina. Methods: Anthropometric and biochemical parameters were measured in 43 patients with MetS and 43 healthy controls. Subjects were genotyped for Pro12Ala (rs1801282) and 1431C>T (rs3856806) SNPs by classic PCR–restriction fragment length polymorphism analysis, and for-681C>G (rs10865710) variant by real-time PCR. Results: The genotype distributions for the three polymorphisms were not significantly different between MetS patients and controls. The Pro12Ala and 1431C>T variants were associated with lower body mass index in the control subjects (p=0.012 and p=0.049, respectively). In this group, the carriers of Pro12Ala had also lower waist circumference compared to the wild-type homozygotes (p=0.045). Conclusions: Results of our preliminary study indicate a beneficial effect of a common Pro12Ala variant on the metabolic phenotype in healthy non-obese subjects.

Contemporary inhabitants of the Balkan Peninsula belong to several ethnic groups of diverse cultural background. In this study, three ethnic groups from Bosnia and Herzegovina - Bosniacs, Bosnian Croats and Bosnian Serbs - as well as the populations of Serbians, Croatians, Macedonians from the former Yugoslav Republic of Macedonia, Montenegrins and Kosovars have been characterized for the genetic variation of 660 000 genome-wide autosomal single nucleotide polymorphisms and for haploid markers. New autosomal data of the 70 individuals together with previously published data of 20 individuals from the populations of the Western Balkan region in a context of 695 samples of global range have been analysed. Comparison of the variation data of autosomal and haploid lineages of the studied Western Balkan populations reveals a concordance of the data in both sets and the genetic uniformity of the studied populations, especially of Western South-Slavic speakers. The genetic variation of Western Balkan populations reveals the continuity between the Middle East and Europe via the Balkan region and supports the scenario that one of the major routes of ancient gene flows and admixture went through the Balkan Peninsula.

Abstract Common variants in MTNR1B, encoding melatonin receptor 1B, have been recently associated with impaired glucose homeostasis and an increased risk for developing Type 2 diabetes (T2D). In this study we investigated the association of MTNR1B variant rs10830963 with T2D and related quantitative traits in a population from Bosnia and Herzegovina (BH). A total number of 268 subjects were recruited in the study (162 T2D patients and 106 nondiabetic controls). Subjects were genotyped for MTNR1B rs10830963 SNP by using hydrolysis probes. Our data showed that the prevalence of the MTNR1B rs10830963 risk G-allele in BH population was 26%. Furthermore, we demonstrated a significant association of MTNR1B rs10830963 variant with fasting plasma glucose (FPG) levels in nondiabetic subjects. Under the additive genetic model, each variant G-allele was associated with an increased FPG levels of 0.29 mmol/L (95% CI 0.12, 0.46, p=0.001). Strikingly, our results also showed a significant association of this MTNR1B polymorphism with increased glycated hemoglobin (HbA1c) levels in nondiabetic subjects (p=0.040, additive genetic model). An association of the MTNR1B variant rs10830963 with T2D risk was not detected in our cohort. In conclusion, here we have demonstrated the association between the common MTNR1B rs10830963 variation and fasting plasma glucose levels in BH population. Furthermore, the influence of this polymorphism on the HbA1c levels was also shown in this study, further strengthening its role in blood glucose control.

Asthma is a disorder characterized by chronic airway inflammation, airway hypersensitivity to a variety of stimuli, and airway obstruction that is at least partially or even completely reversible. To make correct diagnosis of asthma, diagnosis must be based on typical symptoms of asthma and identification of airway hyper responsiveness (AHR) or variable airway obstruction. In some cases, additionally we need to use bronchial provocation test using nonspecific stimuli, such as methacholine or histamine, what is useful for the determination of AHR. However, it is somewhat invasive in nature and it is not available in primary-care clinics or even in many general hospitals. Bronchodilator response (BDR) to short-acting β2-agonists is a valuable test to evaluate variable airway obstruction, which is only useful in patients with reduced lung function at the time of visit. Developed integrated software suite is user friendly tool which considers all this parameters to assist clinicians in the analysis and interpretation of pulmonary function tests data to better detect, diagnose, and treat asthma conditions. A total sum of 72 patient reports with previously diagnosed asthma by clinicians was tested with this tool. The software has performed the classification of asthma in the same way as doctors in 65 (90.27%) cases.

BACKGROUND: Effectiveness of SIT was well documented in many cases and published data. Selection of patients for SIT should be very serious and must include skin test and total and specific IgE measurement. How outcome of SIT correlate with changes of IgE, skin reactivity and overall symptoms reduction is aim of this study. MATERIAL AND METHODS: Skin testing, total and specific IgE measurements were performed before and after each year of treatment. Skin test assessment was performed according to recommendation of Manual of Laboratory immunology. IgE ws performed using ELISA method. Clinical outcome was assessed using AQLQ questionnaire. RESULTS: During five years period 58 asthmatic subjects with home dust and dermathophagoides allergy were treated by SIT. Bseline total IgE was 488,5 IU/ml (SD 78,9), mean specific IgE against dermatophagoides pteronissimus was 36,5 IU/ml (SD 15,2). Subcutaneous tests showed 15-20 mm weal in 43, and more than 21 mm in 15 cases. After 5 years mean total IgE was 227 IU/ml (SD 9,2) and mean specific IgE was 28,2 IU/ml (SD 8,9). Skin tests showed decrease diameter of weal. In 49 out of all patients clinical outcome were very well, and in 9 satisfied (according to AQLQ questionnaire). Using test of correlation, by linear regression, better correlation was shown between of skin testing and AQLQ than in total or specific IgE. So, in vivo skin tests were better predictor for success of SIT, than measurement of IgE. CONCLUSION: Results of skin tests in diagnostic assessment of allergy in asthmatic patients were better predictor of successful outcome of SIT than laboratory measurement of total and specific IgE.

Introduction: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of the hormonally inactive cortisone to active cortisol, thus facilitating glucocorticoid receptor activation in target tissues. Increased expression of 11β-HSD1 in adipose tissue has been associated with obesity and insulin resistance. In this study, we investigated the association of two 11β-HSD1 gene (HSD11B1) polymorphisms with the metabolic syndrome (MetS) and its characteristics in the Bosnian population. Materials and methods: The study included 86 participants: 43 patients diagnosed with MetS and 43 healthy controls. Subjects were genotyped for two HSD11B1 gene polymorphisms: rs846910: G>A and rs45487298: insA, by the high resolution melting curve analysis. Genotype distribution and an influence of genotypes on clinical and biochemical parameters were assessed. Results: There was no significant difference in the mutated allele frequencies for the two HSD11B1 gene polymorphisms between MetS patients and controls. In MetS patients, no significant associations between disease-associated traits and rs45487298: insA were found. Regarding rs846910: G>A variant, heterozygous patients (G/A) had significantly lower systolic (P = 0.017) and diastolic blood pressure (P = 0.015), lower HOMA-IR index (P = 0.011) and higher LDL-cholesterol levels (P = 0.049), compared to the wild-type homozygotes. In the control group, rs45487298: insA polymorphism was associated with lower fasting plasma insulin levels (P = 0.041), lower homeostasis model assessment insulin resistance (HOMA-IR) index (P = 0.041) and lower diastolic blood pressure (P = 0.048). Significant differences between rs846910: G>A genotypes in controls were not detected. Haplotype analysis confirmed the association of rs45487298: insA with markers of insulin resistance in the control subjects. Conclusions: Our results indicate that a common rs45487298: insA polymorphism in HSD11B1 gene may have a protective effect against insulin resistance.

Aim: To study the influence of C-reactive protein (CRP) level in the blood, fibrinogen level and general inflammatory syndrome as the predictors of development of secondary fibrosis in patients with pulmonary tuberculosis (TB). Methods: Concentration of CRP, fibrinogen level was measured using immunoturbidimetric methodIncluding criteria was presentation of TB process in both lungs, as the sign of widespread TB process. Results: We examined 85 patients treated in one year. Mean CRP level was 22,6 mg/mL, range 5-245 mg/mL; normal level (up to 8 mg/mL) was measured in 23,4% patients, medium level (9-20 mg/mL) was measured in 31,3% patients, high level (21-50 mg/mL) were measured in 26,2% patients, and in 23,7% patients CRP were higher than 50 mg/mL. Average fibrinogen level in whole group was 6,9 g/L (SD 5,8). Normal level of fibrinogen (up to 4 g/L) were measured in 6,4% of patients; 4,1-1,0 g/L were measured in 24,6% patients, 10,1-20 g/L were measured in 31,1% patient and level more than 20 g/L were measured in 37,9% patients. Using statistic method of partial correlation statistical significane at level p<0,05 was shown between them. Correlation of CRP and fibrinogen level with appearance of fibrosis on X-ray of the lung was shown. Thereafter, closer correlation was shown with fibrinogen and fibrosis than with CRP and fibrosis. Conclusion: Predicted value of CRP and fibrinogen for pulmonary fibrosis was shown in TB patients. So, attenuation of fibrosis development, possible with antifibroblastic activity of pentoxyphyllin, should be taken in consideration, for prevention of widespread development of lung fibrosis in these patients.