PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis.

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

Association of Inherited Genotype and Severity of Clinical Presentation in Subjects with Verified Pas III Disorder.

Background: Polyglandular autoimmune syndrome type III (PAS III) is combination two most common autoimmune disease: Diabetes mellytus type 1 (DM1) and autoimmune thyroid disease (AITD). Objectives: The aims of the study were a) to define conection between polymorphism of CTLA-4 gene, rs 231775 with PAS III; b) to establish the conection of inherited genotype with severity of clinical features; and c) to estimate the rate of risk for severe clinical presentation among subgroups in study population. Methods: This research included 50 subjects with diagnosed PAS III syndrome, wich are on treatment in clinic for Nuclear medicine and andocrinology KCUS. As methods of research has used: hystory of disesase AND clinical examination. As material is used blood sample. From blood sample DNA was isolated withn Qiamp- DNA-mini kit, with accopanied protocol. Results: In our study, 50 patients with polyglandular autoimmune syndrome type III (PAS III) were examined, and in the study population had 26 female subjects and 24 male subjects. The average age of the participants was 31.64 years, and in the subgroups: group GWT (G-wild type) the average age was 30.20 years, group GM (G-mutated) 32.40 years and group GH (G-heterozygote) 30 , 60 years. Using the Chi-square test, the association between the polymorphism rs231775 and PAS-III was demonstrated, x2 (2.100) = 18.258, where p < 0.0001. Using the Chi-square test, the association between the rs231775 polymorphism and the severity of the clinical picture, x2 (2.50) = 8.531, where p< 0.0140 was proved. The CTLA-4 rs231775 genotypes were also assessed for disease severity. Conclusion: This study suggests that CTLA-4 expression plays a key role in balancing the immune system as well as the response against one's own tissues, and thus in the regulation of autoimmune diseases.

Mediterranean Diet and Type 2 Diabetes Mellitus: A Perpetual Inspiration for the Scientific World. A Review.

For the past 80 years, the effect of the Mediterranean diet on overall health has been a constant topic of interest among medical and scientific researchers. Parallel with the persistent global rise of cases of type 2 diabetes, many studies conducted in the past 20 years have shown the benefits of the Mediterranean lifestyle for people with, or at risk of developing, type 2 diabetes mellitus. However, despite the large body of evidence, concerns exist amongst scientists regarding the reliability of the data related to this topic. This review offers a glimpse of the onset of the Mediterranean diet and follows its significant impact on the prevention and treatment of type 2 diabetes. There is a constant rise in type 2 diabetes cases on the Balkan Peninsula and North Macedonia in particular. Having in mind that North Macedonia, as well as most of the countries on the Balkans have low to middle income, there is a need for a certain affordable dietary pattern to ameliorate the rise in diabetes incidence, as well as improve the glycemic control. We did a review based on the available literature regarding Mediterranean diet and people with or at risk of developing type 2 diabetes mellitus, its effects on glycemic control, lipid profile and metabolic outcome.

Polycystic Ovary Syndrome: A Contemporary Clinical Approach.

Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women during the reproductive period. It is considered a complex metabolic disorder with long-term metabolic, as well as reproductive consequences. Main pathophysiological pathways are related to the increased androgen levels and insulin resistance. Nowadays, genetic origins of PCOS are acknowledged, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation, and disturbed folliculogenesis. Rotterdam diagnostic criteria are most widely accepted and four PCOS phenotypes have been recognized. Metabolic abnormalities are more common in phenotypes 1 and 2. Women with classic PCOS are more obese and typically have the central type of obesity, more prevalently displaying dyslipidemia, insulin resistance, and metabolic syndrome that could be associated with an increased risk of cardiovascular complications during life. Heterogeneity of phenotypes demands an individualized approach in the treatment of women with PCOS. Metabolic therapies involve a lifestyle intervention followed by the introduction of insulin sensitizers including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), as recently sodium-glucose cotransporter-2 (SGLT2) inhibitors. The addition of an insulin sensitizer to the standard infertility therapy such as clomiphene citrate improves ovulation and pregnancy rates. Our current review analyzes the contemporary knowledge of PCOS etiology and etiopathogenesis, its cardiometabolic risks and their outcomes, as well as therapeutic advances for women with PCOS.

Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes.

The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.

Association of IRS1 genetic variants with glucose control and insulin resistance in type 2 diabetic patients from Bosnia and Herzegovina.

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.

Association of FTO Gene Variant (rs8050136) with Type 2 Diabetes and Markers of Obesity, Glycaemic Control and Inflammation.

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 Tesanj 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.

Cardiovascular Risk Factors in Patients with Poorly Controlled Diabetes Mellitus.

INTRODUCTION: Diabetes mellitus(DM) is considered an independent cardiovascular risk factor. Having in mind concomitant occurence of diabetes and other cardiovascular risk factors, it is expected that patients with poor glucoregulation will have more cardiovascular risk factors and higher cardiovascular risk than patients with good glucoregulation. AIM: To compare cardiovascular risk and cardiovascular risk factors between patients with poorly controlled and patients with well-controlled Diabetes mellitus. MATERIAL AND METHODS: Hundered ten patients aged 40-70 years suffering from Diabetes mellitus type 2 were included. Research is designed as a retrospective, descriptive study. Patients with glycosylated hemoglobin (HbA1c) > 7% were considered to have poorly controlled diabetes. The following data and parameters were monitored: age,sex, family history, data on smoking and alcohol consumption, BMI (body mass index), blood pressure, blood glucose, total cholesterol, triglycerides, LDL, HDL, fibrinogen, uric acid. For the assessment of cardiovascular risk, the WHO / ISH (World Health Organization/International Society of hypertension) tables of the 10-year risk were used, and due to the assessment of the risk factors prevalence, the optimal values of individual numerical variables were defined. RESULTS: Differences in the mean values of systolic, diastolic blood pressure, fasting glucose, total cholesterol, LDL cholesterol are statistically significant higher in patients with poorly controlled diabetes. Hypertension more frequently occurre in patients with poorly controlled DM. The majority of patients with well-controlled DM belong to the group of low and medium cardiovascular risk, while the majority of patients with poorly controlled DM belong to the group of high and very high cardiovascular risk. In our research, there was a significant difference in cardiovascular risk in relation to the degree of DM regulation, and HbA1c proved to be an important indicator for the emergence of the CVD. CONCLUSION: There are significant differences in certain risk factors between patients with poorly controlled and well controlled DM. Patients with poorly controlled diabetes mellitus have a higher cardiovascular risk than patients with well controlled diabetes. The value of HbA1c should be considered when assessing cardiovascular risk.

Incidence of prediabetes and risk of developing cardiovascular disease in women with polycystic ovary syndrome.

Our aim was to determine the incidence of prediabetes and risk of developing cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS). This prospective, observational study included 148 women with PCOS, without Type 2 diabetes mellitus (T2DM) and CVD present at baseline. In the fasting blood samples, we measured lipids, glucose, and insulin levels during oral glucose tolerance test, levels of C-reactive protein (CRP), steroids, 25-hydroxyvitamin D (25-OHD), prolactin, thyroid-stimulating hormone, and parathyroid hormone. The follow-up period was 3 years. At baseline, prevalent prediabetes was present in 18 (12%) of PCOS cases and it progressed to T2DM in 5 (3%) of the cases. Incident prediabetes during the follow-up was noted in 47 (32%) women or 4.7 per 1000 persons/year. Prediabetes was associated with elevated body mass index (BMI) (odds ratio [OR] = 1.089, confidence interval [CI]: 1.010; 1.174, p = 0.026), high baseline levels of CRP (OR = 3.286, CI: 1.299; 8.312, p = 0.012), homeostatic model assessment - insulin resistance (IR) (OR = 2.628, CI: 1.535; 4.498, p < 0.001), and high lipid accumulation product (LAP) (OR = 1.009, CI: 1.003; 1.016, p = 0.005). Furthermore, prediabetes was associated with low 25-OHD (OR = 0.795, CI: 0.724; 0.880, p ≤ 0.05). In addition, cardiovascular risk in PCOS women with prediabetes was high (hazard ratio = 1.092, CI: 1.036; 1.128, p < 0.001). We showed association of prediabetes with high BMI, IR, markers of inflammation, LAP, and low serum 25-OHD concentration. IR appears to be more relevant than the other predictors of prediabetes risk in this study. PCOS women are considered as a high-risk population for prediabetes.

Evaluation of the association of vitamin D deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome.

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.

Evaluation of endocrine changes in women with the polycystic ovary syndrome during metformin treatment.

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.

Inflammatory markers in patients with hypothyroidism and diabetes mellitus type 1.

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

The effects of dipeptidyl peptidase-4 inhibitors in treatment of obese patients with type 2 diabetes.

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.

The efficacy of octreotide LAR in acromegalic patients as primary or secondary therapy.

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.

Insulin resistance and lipid accumulation product in corelation to body mass index in women with polycystic ovary syndrome.

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.

Association of NAT2 polymorphisms with type 2 diabetes in a population from Bosnia and Herzegovina.

BACKGROUND AND AIMS: N-acetyltransferase 2 (NAT2) is a drug-metabolizing enzyme, which is genetically variable in human populations. Polymorphisms in the NAT2 gene have been associated with drug efficacy and toxicity as well as disease susceptibility. Recently, an association of NAT2 gene variation with risk of type 2 diabetes mellitus (T2DM) has been suggested. This is the first study performed in a population from Bosnia and Herzegovina (BH) in which the frequency of two common NAT2 polymorphisms, 341T>C (NAT2*5) and 590G>A (NAT2*6) was determined in diabetic patients. METHODS: The frequency of the NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms was analyzed by employing TaqMan SNP Genotyping Assays (Applied Biosystems) in a group of 63 patients with T2DM and 79 nondiabetic subjects. RESULTS: Our data demonstrated that the frequencies of NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms in BH population were in line with the Caucasians genotype data. The NAT2*5 and NAT2*6 alleles were in high linkage disequilibrium (D' = 0.969). Strinkingly, there was a significant difference in genotype frequencies for NAT2*5 (p <0.05) and NAT2*6 (p <0.001) polymorphisms between diabetic and nondiabetic subjects. NAT2*5 polymorphism was associated with 2.4-fold increased risk for developing T2DM (adjusted OR = 2.40, 95% CI = 1.10-5.25, p = 0.028). On the contrary, NAT2*6 variant significantly decreased by 5-fold susceptibility to the disease (adjusted OR = 0.20, 95% CI = 0.09-0.43, p <0.001). CONCLUSIONS: Our data demonstrated that NAT2 genetic variation appeared to be an important risk factor in development of T2DM.

Evaluation of risk markers fluctuation during an initial therapy with rosiglitazon in patients suffering from metabolic syndrome.

The aim of this study was to examine the effects of hypoglycaemic drug-agonists of PPAR-gama receptors-rosiglitazone (Avandia,4 mg - Glaxo Smith Kline) on values of wide-spread risk - markers-fibrinogen, C-reactive protein and uric acid and glicolysated haemoglobin HbA1C as parameter of metabolic control .We included fourty patients with criteria for metabolic syndrome and evaluated results into groups of diabetic and prediabetic patients according to criteria of IDF (International Diabetic Federation)These risk markers and glicolysated haemoglobin HbA1C were observed at the start of therapy, then after four, eight and twelve weeks and results were compared and statistically calculated. Three months initial therapy with rosiglitazone significantly reduced values of HbA1C, fibrinogen and CRP but not uric acid in prediabetic patients.Rosiglitazone initial three months therapy significantly reduced HbA1C, fibrinogen and uric acid, but not CRP in diabetic patients.

The statins in prevention of coronary heart diseases in type 2 diabetics.

UNLABELLED: We aimed to determine whether the administration of statins to type 2 diabetics without pre-existing CHD reduced the incidence of CHD and their effects on cholesterol and CRP levels. All the participants were carefully interviewed, clinically examined, and laboratory tested to exclude conditions likely to provoke an inflammatory response that was an exclusion criterion. EXCLUSION CRITERIA: Serious heart, liver or kidney problems, history of renal transplant, recent history of drug or alcohol abuse, HbA1c>10%, blood pressure >140/90 mmHg, BMI >35 kg/m2, triglycerides >3,0 mmol/dm3. 95 obese diabetics (mean age 60,9 years and BMI=31,59 kg/m2, diabetes duration more than 10 years) without pre-existing CHD, were included in the analysis and were randomized to simvastatin (25 female and 20 male used 40 mg simvastatin daily) or placebo (30 female and 20 male) group. After six months, simvastatin significantly lowered CRP levels by 19%, (p<0,01), cholesterol levels by 18%, TG levels by 8%, LDL levels by 20% and VLDL levels by 17%, whereas there was no change with placebo. After one year the difference sustained between groups. Coronary events were rarely in the simvastatin group (6,6%) than in the placebo group (14%). Coronary revascularizations were 4 in the placebo group and 1 in the simvastatin group. Rate of stroke was more often in the placebo group (18%) than in the simvastatin group (8,8%). So, reduction of acute CHD events is for 7,4% in the simvastatin group. Positive correlation was between CRP and CVD (r=0,29). Statin therapy reduced the risk of coronary heart disease in diabetics without CHD.

Impact of diet, physical activity, lipid status and glycoregulation in estimation of score (systematic coronary risk evaluation) for ten years in postmenopausal women.

The incidence of cardiovascular diseases (CVD) in women, although lower than in men, increases dramatically after the menopause. Diabetes mellitus is a more powerful predictor of CHD risk and prognosis in women than in men. The aim of this study was to promote diet and physical activity (PA) regimen in order to decrease coronary risk in next years in postmenopausal women with impaired glucose tolerance. Methodological approach of this research is to compare data gathered trough prospective and retrospective analysis of anamnestic data, clinical research, diagnostic tests and biochemical parameters of 100 examinees, regarding the glycoregulation, lipid status, body mass indexes, incidence of hypertension, uric acid and fibrinogen level. The SCORE (Systematic Coronary Risk Evaluation) assessment system is derived from a large dataset of prospective European studies and predicts any kind of fatal CVD events over a ten-year period. It was documented that the then year risk of fatal CVD exerted a shift toward the lower percent value in postmenopausal women after proposed diet/PA regimen. In pre-menopausal women the estimated ten year risk of fatal CVD by SCORE was shifted toward the level below 1%. The risk of 15% and above was not documented after diet/physical activity regimen. The prevalence of the atherogenic lipid markers at the beginning and the end of the assay decreased for all investigated lipid parameters in the group of pre-menopausal women what was more than in postmenopausal ones. Presented data indicate that dietary regimen and physical activity are crucial factors in CVD prevention throughout menopause and beyond. Behavioral changes aimed at decreasing food intake and increasing energy expenditure, should be implemented in pre-menopausal period of life.

The effects of treatment of subclinical hypothyroidism on metabolic control and hyperinsulinemia.

We examined the effects of treatment of subclinical hypothyroidism (SH) on metabolic control and hyperinsulinemia. The study included 53 patients ages 53.42+/-3.11 years, BMI = 28.43+/-1.67 kg/m2, with SH. Laboratory evaluation included serum free T3, free T4, TSH, thyroid antibodies, TGL, insulin, C-peptide and glucose during OGTT, HbA1c, CRP and level of lipids. Twelve SH patients (37.7 %) had diabetes mellitus (DM), 14 patients (26.4 %) had glucose intolerance (GI) and 35 patients were obese (66 %). All patients were treated with L-thyroxin (25-50 microg). Patients with DM and GI were treated with diabetic diet, physical activity and previously antidiabetics without change of doses. After the six months of treatment, patients had normal or limited TSH (8.43+/-2.14 vs. 4.22+/-1.23 ulU/ml), level of fasting insulin (176+/-42 vs. 119+/-30 pmol/l) significantly decreased, level of HbA1c (7.2+/-1.3 vs. 5.8+/-0.6 %) decreased as well. The level of fasting and postprandial glucose significantly decreased, level of CRP decreased as well. The level of total cholesterol, as well as triglycerides, HDL and LDL cholesterol were changed. The correlation between TSH and HbA1c was positive and significant. These data support an important role of treatment of SH in support metabolic control and insulin sensitivity.