Maja Malenica

Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes

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.

Association between 11β-hydroxysteroid dehydrogenase type 1 gene polymorphisms and metabolic syndrome

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.

CLASSIFICATION OF METABOLIC SYNDROME PATIENTS USINGIMPLEMENTED EXPERT SYSTEM

This paper presents the development of an Expert System for the classification of metabolic syndrome (MetS). Two-layer feedforward Artificial Neural Network (ANN) with sigmoid transfer function is used for MetS classification. In accordance with international guidelines NHBL/AHA, classification is performed based on following input parameters: waist circumference, blood pressure, glucose level, HDL cholesterol and triglycerides. Samples for training of developed Expert System are obtained from 1083 patients at hospitals in Bosnia and Herzegovina.

CLASSIFICATION OF PREDIABETES AND TYPE 2 DIABETES USINGARTIFICIAL NEURAL NETWORK

In this paper development of Artificial Neural Network for classification of prediabetes and type 2 diabetes (T2D) is presented. For development of this system 310 samples consisting of information about Fasting Plasma Glucose (FPG) and blood test called HbA1c were used. All samples were obtained from several healthcare institutions in Bosnia and Herzegovina, and diagnosis of prediabetes, T2D and healthy patients in this dataset were established by medical professionals. Two-layer feedforward backpropagation network with 15 neurons in hidden layer and sigmoid transfer function, used for classification of prediabetes and T2D in this paper, was trained with 190 samples.

Effect of Cigarette Smoking on Haematological Parameters in Healthy 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.

Association of LPIN1 gene variations with markers of metabolic syndrome in population from Bosnia and Herzegovina.

AIM 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. METHODS This study included 43 patients with metabolic syndrome and 43 healthy controls from General Hospital in Tešanj, Bosnia and Herzegovina. Subjects were genotyped for two LPIN1 gene variations (rs11693809: C>T and rs2716610: C>T) by real time PCR method. RESULTS In control subjects LPIN1 polymorphism, rs2716610: C>T, was significantly associated with a lower body mass index (BMI) (p=0.008) and waist circumference (p=0.008). The second analyzed rs11693809: C>T polymorphism was associated with lower blood HbA1c levels (p=0.048) in a group of MS patients. CONCLUSION Results of our study suggest that rs2716610: C>T polymorphism of LPIN1 gene could have a protective effect against development of metabolic syndrome, while rs11693809: C>T might affect a glucose control in patients with MS.AIM To investigate whether chronic statin treatment after coronary artery bypass grafting (CABG) protects patients from major cardiac events and provides percutaneous coronary intervention (PCI) free survival. METHODS A total of 232 patients with previous CABG and chronic statin therapy were selected retrospectively and were divided into two groups according to a dosage of atorvastatin per day, e. g., 20 mg or 40 mg. Groups were compared for the major cardiac events and freedom from PCI by Kaplan Meier analysis as the primary end point. Patency of grafts including left internal thoracic artery (LITA) and saphenous vein (SVG) and progression of non-grafted native vessel disease were also evaluated as secondary end points. RESULTS Cardiac mortality, periprocedural myocardial infarction (MI), target vessel revascularization and percutaneous coronary intervention free survival were as follows: 2.9% versus 2.1% (p=1.000); 16.1% versus 21.1% (p=0.331); 56.93% versus 52.63% (p>0.005); 58.4% versus 63.2% (log-rank test; p= 0.347) in atorvastatin 20 mg and atorvastatin 40 mg groups, respectively. However, these results were not statistically significant between two groups (p>0.005). Patency of openness of grafts including LITA and SVG and progression of non-grafted native vessel disease were similar between groups (p=0.112, p=0.779, p=0.379 and p=0.663, respectively). CONCLUSION Low-dose long-term statin treatment had similar outcomes on major cardiac events and identical rate of freedom from percutaneous coronary intervention after coronary artery bypass grafting compared with high-dose long-term statin treatment. It is better to start from low dose statin treatment after surgical interventions.

Effects of the PPARG Gene Polymorphisms on Markers of Obesity and the Metabolic Syndrome in Bosnian Subjects

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.

Use of Databases for Early Recognition of Risk of Diabetic Complication by Analysis of Liver Enzymes in Type 2 Diabetes Mellitus

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.

Association of FTO Gene Variant (RS8050136) with Type 2 Diabetes and Markers of Obesity, Glycaemic Control and Inflammation

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.

Anaphylaxis during specific subcutaneous immunotherapy against ragweed allergen -- case record

Background Recommended by Resolution of Immunotherapy, issued by EAACI, Specific immunotherapy (SIT) was established as a mainstream method of treating allergic diseases. SIT produces long term challenges. SIT team should be aware that at first injection of allergen, the immunotherapy may cause a long lasting reaction. Anaphylaxis during SIT is very rare, but it is possible. We’ve experienced anaphylaxis after four year of SIT, against ragweed allergen.