ACTA ENDOCRINOLOGICA (BUC)

Context. Diverse physiological or pathological events which are stimulated or contributed by HGF/c-Met pathway overlap by processes that play roles in etiopathogenesis of diabetes. Objective. In this study, it was aimed to analyse hepatocyte growth factor (HGF) and its receptor c-Met by immunohistochemistry in the heart and aorta tissues of diabetic and insulin-treated diabetic rats. Subjects and Methods. Accordingly, 21 rats were (equally) divided into three groups: Control (C), Diabetic (D), and Insulin-treated Diabetic (D + I). Rats were treated with Streptozotocin (STZ) (45 mg/kg, i.p.) to induce diabetes. Rats in the control group were given saline once a day for 8 weeks, while rats in the D + I group received 6 U/kg NPH insulin once daily for 8 weeks. The heart and aorta tissues were examined with immunohistochemistry, using antibodies against HGF and c-Met. Results. HGF and c-Met expressions were observed to be increased both in heart and aorta tissues in group D, whereas they decreased in group D+I. Conclusions. As a result, insulin treatment was determined to have a reducing effect on the increased expression of HGF and c-Met in diabetic heart and aorta. According to our results, increased HGF ve c-Met values observed in the myocardium and aorta in diabetes, are shown to increase in parallel to tissue damage and decrease by insulin treatment which is an effective therapy method.

Context. With more studies investigating effects of high serum lipid levels, new findings are emerging regarding the damage these biomolecules may cause. Aim. In this study we aimed to find a relation between neuropathy and hypertriglyceridemia in patients with metabolic syndrome (MS). Material and methods. One hundred and twenty subjects (Ninety subjects with metabolic syndrome and 30 healthy controls) were included in the study. Subjects with MS were divided into three groups. HbA1C levels of the subjects were < 5.7% in group A, ≥ 5.7% - < 6.5% in group B, and ≥ 6.5% - < 8.0% in group C. Pin-Prick test and Semmes- Weinstein Monofilament were used for neurological examination. Electromyography was performed to patients with neuropathy to support the diagnosis. Results. Neuropathy prevalence was found to be higher in the subjects with metabolic syndrome compared to control group. (9.9 %; 16.65 %; 23.31 % vs. 3.3%; in group A, group B, group C vs. healthy control group respectively) (p=0.003 for group A, p=0.0002 for group B, p=0.0002 for group C). There was an association between triglyceride levels and neuropathy in group C. Conclusion. Patients with MS may have more neuropathy risk than we estimate.

Introduction. Thyroid diseases may cause endothelial dysfunction. Asymmetric dimethylarginine (ADMA) levels in patients with thyroid dysfunction were analyzed by few studies.\r\nAim.We aimed to compare ADMA levels in patients with hyperthyroidism in a cohort free of cardiovascular risk associates such as diabetes or chronic renal failure with further comparison with healthy control subjects.\r\nMaterials and methods. The study took place in Duzce University Medical Faculty, Cardiology and Internal Medicine\r\nDepartment during the year 2010. The study group consisted of patients with hyperthyroidism (overt and subclinical). The patients with renal failure, diabetes and severe\r\nhypertension were excluded.\r\nResults. Mean ADMA level was 1.04 ? 0.43 &#956;mol/L in the hyperthyroid group and 0.68 ? 0.21 &#956;mol/L in the control group (p&#8804;0.001). The comparison of patients with hyperthyroidism according to the etiology (three groups as Graves?, multinodular goiter and thyroiditis) did not show any significant difference.\r\nConclusion. Asymmetric dimethylarginine increases in patients with hyperthyroidism regardless of the etiology.\r\nThe increase of ADMA levels is independent of known major cardiovascular risk factors. It may reflect the possible counteraction of endothelial dysfunction in the pathogenesis of atherosclerosis in hyperthyroidism beyond the known cardiovascular risk factors.

Background. sRANKL (soluble receptor activator of nuclear factor-kB ligand) and OPG (osteoprotegerin) represent a novel cytokine system with pleiotropic effects on bone remodeling.\r\nAim. The aim of this study was to assess the implications of serum levels of sRANKL, OPG and E2 (estradiol) in the process of bone remodeling of postmenopausal women with osteoporosis.\r\nMethods. The study was performed on 74 patients with postmenopausal osteoporosis, divided into two groups of patients according to the duration of estrogenic deprivation, compared with a control group (n= 20 postmenopausal women without osteoporosis). The serum levels of the enunciated markers were measured by ELISA technique.\r\nResults. In the group I (n= 48, bellow 15 yrs of estrogenic deprivation) the serum levels of sRANKL were 67.63?3.55 pg/mL (p<0.002), those of OPG were 42.15?0.55 pg/mL (p<0.002) and the levels of E2 were 28.32?1.78 pg/mL (p<0.004). In the group II (n= 26, over 15 yrs of estrogenic deprivation) the serum levels of sRANKL were 49.26?2.85 pg/mL (p<0.003), those of OPG 27.78?1.04 pg/mL (p<0.003) and the serum levels of E2 were 19.66?1.23 pg/mL (p<0.002). In the control group (n=20), the serum levels of sRANKL were 32.48?3.03 pg/mL, those of OPG 38.05?4.89 pg/mL and the serum levels of E2 were 43.07?4.04 pg/mL.\r\nConclusions. The serum levels of sRANKL are significantly higher in postmenopausal women with osteoporosis versus postmenopausal women without osteoporosis, attesting osteoclasts activation. The serum levels of OPG in postmenopausal women with osteoporosis were increased in group I, suggesting the osteoblastic activation and decreased in group II, probably secondary to the stimulation of osteoblastic apoptosis.

Aim. To assess the levels of s BGP and BAP and correlate them with the rate of bone remodelling.\r\nPatients and Methods. The study was performed on 74 cases with postmenopausal osteoporosis, divided into two groups, according to the duration of estrogenic deprivation, compared with a control group (n= 20, postmenopausal women without osteoporosis). The serum levels of the discussed markers were measured by ELISA technique. BMD was measured using the DXA technique with the assessment of T score.\r\nResults. In the group I: BGP were 20.12?0.87ng/mL (p<0.03), those of BAP 13.76?0.6&#956;g/mL (p<0.001) and sT spine were -3.63?0.65DS (p<0.001). In the group II: BGP were 15.12?1.55ng/mL (p<0.05), those of BAP 11.88?0.38&#956;g/mL (p<0.001) and sT spine were -3.78?0.36DS (p<0.001). The control group presented: BGP of 16.22?1.62ng/mL, those of BAP of 8.68?0.44&#956;g/mL and sT spine of -1.78?0.11DS. The serum levels of BGP in postmenopausal osteoporosis cases were increased in group I (suggesting an osteoblastic activation) and decreased in group II (probably secondary to the stimulation of osteoblastic apoptosis). The serum levels of BAP are significantly increased\r\nin postmenopausal osteoporosis versus control group, attesting osteoblastic activation.\r\nConclusion. Bone resorption begins gradually to outrun a new bone formation rhythm associated with low BMD.

Background. Insulin resistance (IR) is a component of type 2 diabetes and metabolic syndrome and it increases in the presence of chronic inflammation. Lately, “neutrophilto- lymphocyte ratio” (NLR) has been used as an indicator of inflammation. This study evaluates the association between IR and NLR in obese women. Material and methods. Obese female patients who were followed up in a university hospital for the last two years were included in the study. Homeostasis model assessment of IR (HOMA-IR), C-peptide, NLR, bioelectrical impedance measurements of 83 patients were analyzed. Results. The C-peptide levels of our patients showed a highly significant correlation with HOMA-IR (p<0.001). A significant positive correlation was found between fasting plasma C-peptide levels and NLR (r=0.36 and p<0.003) in obese women. The increase in C-peptide levels had a significant effect on the increase in NLR (r2=0.31, p=0.002), however insulin had no similar effect on NLR (r2=0.01, p=0.544). Conclusion. Plasma C-peptide levels are better correlated with NLR compared to other parameters of IR. C-peptide may be used as an efficient laboratory marker with high relevance in IR and chronic inflammatory conditions in obese women.

Context. Insulin resistance has been detected in a majority of patients with polycystic ovary syndrome (PCOS). Elevated neprilysin levels are associated with insulin resistance. Objective. The present study aims to investigate plasma neprilysin and its relationship with endocrine and metabolic characteristics in patients with PCOS. Subjects and Methods. Thirty-five premenopausal PCOS patients and 35 healthy volunteers of similar age were included in the study. Demographic characteristics, biochemical and hormonal findings and also plasma neprilysin levels were determined in these patients and healthy controls. Results. In our study, HOMA-IR values were significantly higher in PCOS patients (3.3 ± 1.8) compared with the controls [(1.6 ± 1), p<0.01]. Plasma neprilysin levels were significantly higher in the PCOS group compared to the control group (1502.1 ± 1641.2 vs. 764.6 ± 562.6 pg/ mL). There was no difference in plasma neprilysin levels when PCOS patients were classified as overweight-obesity (BMI≥25kg/m2) or non-obesity (BMI<25kg/m2). Conclusion. Our findings revealed significantly higher levels for plasma neprilysin and HOMA-IR values in PCOS patients when compared to controls. No significant differences were noted between obese PCOS patients and non-obese PCOS patients in terms of plasma neprilysin levels.

Background. In most type 1 and mixed forms of amiodarone-induced thyrotoxicosis (AIT), after restoration of euthyroidism and whether amiodarone can be withdrawn, an ablative therapy (thyroidectomy or radioiodine) is required. Radioiodine ablation of the thyroid was reported to prevent recurrence of AIT after amiodarone reintroduction.\r\nAims. To assess the efficacy and safety of radioiodine treatment in type 1 and mixed forms of AIT.\r\nPatients and methods. 9 patients (6M/3F) with type 1 and mixed form of AIT, mean age 62.2 ? 13.3 years (range: 50-85 years), pretreated with methimazole, received radioiodine treatment. The underlying thyroid disease was Graves disease (n= 5), toxic multinodular goiter (n= 3) and toxic adenoma (n=1). TSH, total T3, total T4, free T4, TPOAb were measured by radioimmunoassay; radioiodine uptake, thyroid ultrasonography, color flow Doppler ultrasonography were performed.\r\nResults. Multiple radioiodine doses were required in 4 out of 9 patients. Pretreatment 24 hours radioiodine uptake exceeded 10% in 12 out of 16 doses. Mean cumulative dose was 23.17 ? 17.48 mCi 131I (range 6-50 mCi). The period between amiodarone withdrawal and 131I administration was 11.72 ? 12.45 months (range: 2-41 months). Mean cumulative 131I dose was higher in AIT due to toxic multinodular goiter and toxic adenoma (30.25 ? 20.09, range: 11-50 mCi) versus Graves disease (17.5 ? 14.76, range: 6.5-40 mCi). In one patient with toxic adenoma, thyroidectomy was contraindicated due to a comorbidity-central core disease - a non-progressive congenital myopathy, associated with an increased risk for malignant hyperthermia. Hypothyroidism occurred in all patients but one (euthyroid), within 14 ? 3 months (range: 5-27) after the first radioiodine dose. Sinus rhythm was restored in 3 out of 5 patients. One case of radiation thyroiditis occurred after a single 6.5 mCi 131I dose.\r\nConclusion. Radioiodine ablation therapy is an effective and safe alternative in patients with type 1 and mixed forms of amiodarone-induced thyrotoxicosis. Since amiodarone should need sometimes to be restarted, post radioiodine hypothyroidism should be viewed as a goal rather than a complication.

Context. Predictive equations estimate total fat mass obtained from multiple-site ultrasound measurements; however, the predictive equation of total fat mass has not been investigated solely from abdominal subcutaneous fat thickness. Objective. To develop regression-based prediction equations using abdominal subcutaneous fat thickness for predicting fat mass, and to explore the validity of these predictive equations. Design. Cross-sectional study. Subjects and Methods. Twenty-seven males and eighteen females were randomly divided into two groups as the model prediction and the validation. Total body fat mass was determined by dual-energy X-ray absorptiometry. The linear regression analysis was used to predict equations for total body fat mass from abdominal subcutaneous fat thickness acquired by ultrasound. Then, these predictive equations were tested on the validation group. Lin’s concordance correlation coefficient (CCC) was used as a further measure of agreement. Results. When fat mass prediction equations were tested on the validation groups, measured- and estimated-total fat masses in males (p=0.9) and females (p=0.5) were found similar. A good level of agreement between measurements in males (CCC=0.84) and females (CCC=0.76) was attained. Conclusion. The abdominal subcutaneous fat thickness obtained from a single region by ultrasound might provide a non-invasive and quick evaluation.

Context. Sodium Glucose Co-Transporter-2 inhibitors (SGLT2i) are oral antidiabetic agents that can be used with insulin in the treatment of type 2 diabetes mellitus, known for cardiovascular and renal benefits. Dapagliflozin and empagliflozin are available in Turkey and we aimed to evaluate real-life data of using these two molecules with other oral antidiabetic drugs (OAD) or insulin. Subjects and methods. 119 patients (59 women, 60 men) files who had started SGLT2i between 2017-2019 were examined retrospectively until 6 months after the treatment change. Patients’ weight, body mass index (BMI), insulin doses, fasting blood glucose, HbA1c, lipid profile, spot urine albumin/creatinine ratio, e-GFR values, ALT, AST, uric acid levels were evaluated at baseline, 3 months and 6 months. Results. 41.2% of patients were using dapagliflozin and 58.8% were using empagliflozin. After 6 months of follow-up, HbA1c decreased from 8.27% to 7.45% (p<0.001). Daily total insulin dose decreased from 84.75 to 75.58 U/day in 3 months (p<0.004). Weight and BMI decreased significantly at 6 months. ALT, AST decreased significantly in patients using insulin (p 0.001 and 0.007), whereas spot urine microalbumin/creatinine ratio decreased at 3 and 6 months (p 0.005 and 0.020). A significant decrease was also observed in uric acid levels (p: 0.026). Conclusions. Dapagliflozin and empagliflozin have beneficial effects on decreasing glycemic parameters, weight, transaminases, uric acid and microalbuminuria in the real life environment. We also observed that SGLT2i and insulin combination is as safe and effective as combination with OAD.