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B. Heljić, Z. Velija-Ašimi, Azra Bureković, Vanja Karlović, Azra Avdagić, M. Cemalović

Introduction: The increased risk of coronary artery disease in diabetics could be explained by the lipoprotein irregularities associated with diabetes mellitus. The primary aim of this study is to examine the role of apple vinegar and syrup in the management of type 2 diabetes mellitus.Methods: The interventional study included 500 participants (195 men and 305 women) with dyslipidemia and prediabetes or type 2 diabetes mellitus, aged 50-70 years, living in Sarajevo area. Patients were recruited from 5 outpatient diabetes counselling departments and treated with natural apple vinegar and syrup supplementation over a period of five weeks. The patients have been evaluated before treatment and 5 weeks after the treatment. During the study, dosage of drugs for diabetes or prediabetes was not changed.Results: After 5 weeks of supplementation with apple vinegar and syrup waist circumference (p=0.016), total cholesterol (p=0.01), low density lipoprotein (LDL) cholesterol (p=0.008) and triglycerides (p=0.019) were significantly reduced, as well as blood pressure (-14%). Study results show decrease of mean fasting blood levels of glucose, but statistically not significant (p=0.058). The body mass index also decreased insignificantly (p=0.089). The high density lipoprotein cholesterol level was not increased significantly after supplementation (p=0.26).Conclusion: According to our results, apple vinegar has important role in reduction of total cholesterol levels, triglycerides, LDL cholesterol and waist circumference in patients with type 2 diabetes. Also, it has positive effect on blood pressure.

Z. Velija-Ašimi, Azra Bureković, K. Dizdarevic

In total 17 patients with acromegaly diagnosed at Endocrinology Clinic in Sarajevo, somatostatin sensitive (10 females and 6 males, age range 37-65 years, 6 patients with microadenoma and 10 patients with macroadenoma) were treated with octreotide LAR. Follow-up period was 4 years (2009-2014). Ten patients were treated with surgical and octreotide treatment. One patient was treated with surgical, octreotide and gamma-knife treatment and six patients were treated only with octreotide LAR. The concentration of human Growth Hormone (hGH) and Insulin-Like Growth Factor I (IGF-1) were evaluated before treatment and every 6 months during follow-up period of 4 years, while magnetic resonance imaging (MRI) was taken before the treatment and every year during follow-up period. Thirteen patients received octreotide 30 mg/28 days, two patient received 20 mg and other two 60 mg/28 days. Statistical data analysis includes basic statistics, descriptive statistics and nonparametric statistics (Friedman, Wilcoxon signed ranks test and Mann–Whitney U-test). Statistical significance was set as p < 0.05.Copy and paste your text content here, adjusting the font size to fit. Objective

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.

AIM To evaluate the association of vitamin D (VD) deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome (PCOS). METHODS Of the total of 140 women, thirty obese and thirty nonobese, aged 20-40 years, were included in the study. Inclusion criteria were the women with normal level of thyroid-stimulating hormone (TSH), prolactin (PRL), parathyroid hormone (PTH), and calcium, and those who had not received any medication or VD supplementation within the last 6 months. Serum 25- hydroxyvitamin D (25(OH)D), C-reactive protein (CRP), lipid profile, fasting serum glucose, basal insulin, homeostasis model analysis of insulin resistance (HOMA-IR) index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen, total testosterone, dehidroepiandrostendion-sulphat (DHEA-S), androstendione, and sex hormone binding globulin (SHBG) were determined at follicular phase. RESULTS Body mass index (BMI), weight, waist, lipids, and CRP were significantly higher in obese than in non-obese PCOS women (p=0.000). Meanwhile, insulin and HOMA-IR were also higher in the obese PCOS (p less than 0.000), and so was the fasting glucose (p=0.004). Furthermore, obese PCOS showed significantly higher level of LH (p=0.012), but lower level of progesterone (p=0.001) and androstendione (p=0.006) than in non-obese PCOS. In total 68% of PCOS women had VD deficiency but without significant difference among groups according to BMI. There was no association of VD deficiency with gonadotropins and sex hormones except SHBG. CONCLUSION Insulin resistance was a better independent risk factor for the presence of vitamin D deficiency than SHBG. The insulin resistance and vitamin D deficiency significantly predicted the obesity risk in PCOS women.

The aim of study was to evaluate endocrine changes in PCOS women during metformin treatment. One hundred women with PCOS, aged 20-40 years were included. A complete hormonal and metabolic pattern was recorded for each subject every 6 months. Metformin treatment after 6 and 12 months significantly reduced weight, BMI, waist circumference, insulin and HOMA-IR (p=0.000) with high differences of variances within repeated measurements. There was significant reduction of PRL, testosterone and estradiol (p=0.000) with small differences within repeated measurements. Metformin did not have effect on TSH. However, results showed important reduction of CRP, LH, LH/FSH, androstendione, DHEA-S and progesterone (p=0.000) with moderate differences within measures. Metformin restored menstrual cyclicity in most participants. At baseline in study group was 69% women with oligomenorrhoea, amenorrhoea or polymenorrhoea. After 12 months of treatment, only 20% PCOS women had irregular menstrual cycle (p=0.000). Hirsutism was also reduced. Intriguingly, during first 6 months of treatment in PCOS women 9 pregnancies occurred (p=0.000), while during last 6 months treatment were 2 pregnancies (p=0.317), in total 11(13%). Multiple regression model revealed that the presence of anovulation in PCOS women was strongly associated with BMI, waist, FSH and age. Insulin resistance was significantly predicted by BMI, cholesterol, progesterone and presence of hirsutism. The metformin therapy significantly improved insulin resistance, imbalance of endocrine hormones, hirsutism and menstrual cyclicity in women with PCOS. The most important predictors for duration of metformin treatment in PCOS women were testosterone, progesterone, FSH, CRP and presence of anovulation.

Amela Dizdarevic-Bostandic, Azra Bureković, Z. Velija-Ašimi, Amina Godinjak

INTRODUCTION The accumulation of macrophages what happens in atherosclerotic process is associated with increased concentration of fibrinogen and CRP (C-reactive protein), and these two markers of inflammation are considered early signs of atherosclerosis. AIM The aim of the study was to compare levels of inflammatory markers (CRP and fibrinogen) and HbAlc as a parameter of quarterly blood glucose control in patients with both diabetes mellitus type 1 and hypothyroidism who have ischemic heart disease with the patients with same autoimmune diseases, but without ischemic heart disease. PATIENTS AND METHODS This prospective study included 30 patients who were all diagnosed with both hypothyroidism and diabetes mellitus type 1. Patients were divided into two groups according to the persistence of ischemic hearth disease. The first group (I) included patients with previously diagnosed ischemic heart disease (N = 12), and second group( II) was without ischemic heart disease (N = 18). CRP, fibrinogen and HbA1c as a parameter of quarterly glycemic control were measured in all patients. RESULTS CRP level in group I was higher than in group II, and the difference between groups is statistically significant (t = -4125, p = 0.0001). Fibrinogen level was also significantly higher in first group (t = -4.7; p = 0.0001). Both, CRP and fibrinogen levels were in two groups above the upper reference values. The average value of HbAlc as a parameter of quarterly glycemic control in both groups showed bad controlled diabetes mellitus, 8.77% (+/- 1.89) vs. 8.16% (+/- 1.71), but among the groups there were not statistically significant differences (t = -0.921 p = 0.365). CONCLUSION Patients with both type 1 diabetes mellitus and hypothyroidism who have ischemic heart disease had significantly higher levels of inflammatory markers: CRP and fibrinogen, than patients with the same diseases who did not have coronary heart disease, while HbAlc as a parameter of quarterly blood glucose control did not differ between groups, but in both groups showed values that corresponded to poor disease control. While future medical research has not reached full answers to the atherosclerotic process, seems reasonable therapeutic affect all identified biochemical markers associated with this process. Key

INTRODUCTION Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antihyperglycemic drugs that block degradation ofincretin hormones. GOAL To assess the effects oftreatment with DPP-4 inhibitors on glucoregulation and body weight in obese patients with type 2 diabetes mellitus. PATIENTS AND METHODS The study included 9 females and 9 males with type 2 diabetes (n=18), BMI=31.24 +/- 2,26 kg/m2, mean age 58 +/- 6,8 years. The patients have been thoroughly evaluated before treatment, and 6 months after treatment with DPP-4 inhibitor (sitagliptin) in combination with metformin. RESULTS After 6 months of treatment with DPP-4 inhibitors in combination with metformin HbAlc (-1,49%)., FBG (-3.75 mmol/L) and PBG (-5.79 mmol/L) significantly reduced (p=0.000). Mean body weight also significantly reduced (-12.5%; p=0.000). Reduction of mean fasting insulin was 5.46 mIU/L or 27% (p=0.000). Mean HOMA-IR change was -1.64 (p=0.000). Also there was significant decreasing of systolic blood pressure (p=0.001), cholesterol (p=0.004), triglycerides (p=0.001), LDL (p=0.002) and increasing of HDL (p=0.002). Hypoglycaemia was not registered in any of the patients. CONCLUSION These results show that in obese patients with type 2 diabetes, DPP-4 inhibitors treatment in combination with metformin was associated with improvements in glycaemic control, and a reduction in body weight.

INTRODUCTION Women with Polycystic Ovary Syndrome (PCOS) are at increased risk for cardiovascular morbidity and metabolic disorders including: dyslipidaemia, hypertension, insulin resistance, gestational diabetes, type 2 diabetes, systemic inflammation and endothelial dysfunction. The prevalence of obesity and insulin resistance in women with PCOS is significantly higher compared to the general population. Lipid accumulation product is a new, cheap and easily available predictor for metabolic syndrome both in general population and in women with PCOS. MATERIALS AND METHODS The study included 50 patients at the Clinic of Endocrinology, Diabetes and Metabolic Disorders, Clinical Center University of Sarajevo. All patients were diagnosed with PCOS according to the Rotterdam ESHRE criteria and were divided into two groups according to their body mass index (BMI). A prospective study established the following parameters: anthropometric measurements (waist circumference, height, weight), BMI, and serum triglycerides and insulin resistance. LAP was calculated using the formula: LAP (women) = [waist circumference (cm)-58] x [triglycerides (mmol/L)]. RESULTS Waist circumference in women with BMI < or = 24.9 kg/m2 was 31 cm lower than waist circumference in women with a BMI > 25 kg/m2. Mean triglyceride value of the patients in group BMI < or = 24.9 kg/m2 was 1.15 mmol/l lower than the mean value of triglycerides in women with a BMI > 25 kg/m2. Insulin resistance was present in 66.7% in group with BMI < or = 24.9 kg/m2, and in 75.0% in the group with BMI > 25.0 kg/m2. LAP was shown to be a marker for the differentiation of insulin-resistant and nonresistant patients with a cut-off value of 17.91. CONCLUSION Patients with PCOS and BMI < or = 24.9 kg/m2 were significantly different from those with BMI > 25 kg/m2 in the values of body weight, waist circumference and triglycerides. There was no statistically significant difference in insulin resistance. LAP values were higher in patients in the group with BMI > 25 kg/m2. LAP was a marker for differentiation of insulin--resistant and non-resistant women with PCOS.

Objective: The objective of this study was to investigate the efficacy of octreotide therapy in acromegalic patients as primary or secondary therapy. Methods: Ten acromegalic patients diagnosed at the Endocrinology Clinic in Sarajevo (seven females and three males, mean age 55.2 ± 7.2 years, age range 40–65 years, five patients with microadenoma and five patients with macroadenoma) were treated with octreotide. Among them, 60% of patients were operated on and the majority of the procedures were performed transnasaly (90%). That group of patients had recidivism of disease (pituitary adenoma and acromegaly). The concentration of human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1) was evaluated at 0, 6 and 12 months, while magnetic resonance imaging (MRI) was taken before the treatment and 12 months after. Eight patients received octreotide 30 mg/28 days, one patient received a dose of 20 mg and the other received 60 mg/28 days. Results: Before treatment growth hormone (GH) levels were 50.87 ± 10.56 ng/ml (range: 26–64.9), IGF-1 were 776.66 ± 118.40 ng/ml (range: 526–934). Four patients (40%) were treated with primary octreotide treatment and six patients (60%) with secondary somatostatin analog treatment. At the beginning of therapy, there were no differences in terms of age, HGH levels and IGF-1 levels between primary and secondary treatment groups (p > 0.05). The difference between groups was only in regard to the size of tumors (p = 0.01). After 6 and 12 months the GH levels decreased to 1.61 ± 0.86 ng/ml (range: 0.7–2.65) and 1.85 ± 2.40 ng/ml (range: 0.0–8.3), respectively, while the IGF-1 became 305.90 ± 43.19 ng/ml after 6 months of treatment (range: 240–376) and 256.99 ± 71.43 ng/ml after 12 months of octreotide treatment (range: 126–325), respectively. The pituitary adenomas size prior to treatment was 9.57 mm, while after 12 months of treatment, the size decreased to 8.0 mm. After therapy, a GH decrease to less than 2.5 ng/ml was achieved in 90% of cases; tumor size decrease was achieved in 60% while normalization of IGF-1 was achieved in 100% of the patients, respectively. All differences about HGH and IGF-1 in each group were statistically significant (p < 0.05). In the group of acromegalic patients treated with octreotide LAR as primary therapy, the difference was more significant for GH and IGF-1 than for adenomas size. Conclusions: Octreotide treatment of acromegaly not only decreases GH and IGF-1 concentrations, but also appears to diminish the size of the tumor in about 60% of cases. The somatostatin analogs are more efficient in the primary treatment of acromegalic patients, due to the fact that primary therapy is as effective as secondary therapy but primary therapy has small advantages when compared with secondary octreotide therapy because no surgical treatment is required before.

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