Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

BACKGROUND AND AIMS: Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. METHODS: The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. RESULTS: Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. CONCLUSION: Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

Is isoenergetic high-intensity interval exercise superior to moderate-intensity continuous exercise for cardiometabolic risk factors in individuals with type 2 diabetes mellitus? A single-blinded randomized controlled study.

The aim of this study was to compare the effect of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) with equal energy expenditure on glycaemic and cardiometabolic risk factors in people with Type 2 Diabetes Mellitus (T2DM) when compared to the control. Sixty-three people with T2DM were randomly assigned to HIIT, MICT, or non-exercising controls. Individuals were trained with HIIT at 90 and 30% of their VO2peak (1:2 min ratio) starting from 8 up to 16 intervals and MICT at 50% of VO2peak, on a cycle ergometer, 3 times/week for 12 weeks under supervision. The primary outcome measure was the change in HbA1c. Aerobic capacity, cardiovascular responses, anthropometric measures, body composition, glycaemic, and cardiometabolic risk factors were measured at the beginning and the end of the 12-week training period. There was no significant difference between HIIT and MICT or when compared to the control for HbA1c, glucose, insulin resistance, blood lipids, cardiovascular responses, anthropometric measures, body composition, and abdominal and visceral fat (padj > 0.05). HIIT and MICT increased VO2peak significantly compared to controls (p < 0.05) but not to each other (p > 0.05). Both HIIT and MICT improved VO2peak and HbA1c after 12 weeks of training compared to their baseline, furthermore, only MICT caused additional improvements in cardiovascular responses, anthropometric measures, and abdominal fat compared to baseline (p < 0.05). As a conclusion, isoenergetic HIIT or MICT did not improve HbA1c. The two protocols were equally efficient for improvement in aerobic capacity but had little effect on other cardiometabolic factors.Trial registration: ClinicalTrials.gov identifier: NCT03682445.HighlightsHIIT and MICT with equal energy expenditure were equally efficient for aerobic capacity compared to controls.Isoenergetic HIIT or MICT were not superior for improving HbA1c.Isoenergetic HIIT and MICT were not superior to each other for anthropometric measures, body composition, and cardiometabolic risk factors.

Relationships among Bone Metabolic Markers, Body Fat Composition and Carotid Intima-Media Thickness in Premenopausal Obese Women.

Osteocalcin (OC) is inversely related to body fat distribution and fasting glucose levels. We sought to observe the effect of OC on fat distribution and subclinical atherosclerosis as measured by carotid intima-media thickness (CIMT) in premenopausal obese women. In this prospective observational study, totally, 73 premenopausal obese women (aged 17-55 years) and 53 healthy women (aged 20-50 years) with normal weight were included as controls. Anthropometric measurements, total fat and fat ratio, insulin, fasting blood glucose, and OC levels were estimated. Ultrasonography was used to assess fat distribution, and fat thickness was measured in 4 regions. Subcutaneous fat (SCF), visceral fat (VF), and preperitoneal fat (PPF) thicknesses were considerably higher in obese subjects (p<0.01) than healthy controls, while OC levels were significantly lower. No correlation was observed between OC levels and SCF, VF, or PPF. In a multiple regression analysis, OC was significantly positively associated with SCF (p=0.04, Beta=0.284). No associations were observed between OC levels and VF, PPF, or CIMT. A significant association was observed between parathyroid hormone (PTH) and VF (p=0.021, Beta=0.284), and vitamin D levels were inversely associated with VF (p=0.002, r=-0.366). OC levels were lower in premenopausal obese women than normal-weight healthy controls, but OC exhibited no correlation with VF or PPF, and only a weak positive association with SCF. Additionally, VF was positively correlated with PTH and inversely correlated with vitamin D. These results suggest that OC may be an early indicator of lipid accumulation in te subcutaneous area and development of atherosclerosis.

Effects of Treatment Adherence on Quality of Life in Hypoparathyroid Patients.

OBJECTIVES: This study aimed to evaluate the current situation of hypoparathyroid patients and to investigate the relationship between treatment adherence and quality of life. STUDY DESIGN: Prospective, multicentre study. METHODS: Adult patients presenting with the diagnosis of hypoparathyroidism to 20 different endocrinology clinics were included. They were receiving conventional therapies for hypoparathyroidism, using calcium, active vitamin D, and magnesium. We collected data on demographic features, disease- and treatment-related information, and results of routine laboratory tests, treatment adherence, and presence of complications. Beck Depression Inventory, Beck Anxiety Inventory, and Short Form-36 quality of life assessments were administered. RESULTS: Among the 300 patients studied, 60.7% were adherent to their treatment, and 34.1% had complications. Anxiety and depression scores were significantly higher in non-adherent versus treatment-adherent patients (p<0.001 and p=0.001, respectively). Most of the domains of quality-of-life scores were also significantly lower in non-adherent patients. Both anxiety and depression scores showed significant, negative correlations with serum calcium and magnesium concentrations (r=-0.336, p<0.001 and r=-0.258, p<0.001, respectively). CONCLUSIONS: Nearly 40% of the patients were non-adherent to conventional treatment for hypoparathyroidism, and such patients had higher anxiety and depression scores and poorer quality of life scores. Conventional treatment might not be sufficient to meet the needs of patients with hypoparathyroidism. In addition to seeking new therapeutic options, factors influencing quality of life should also be investigated and strategies to improve treatment adherence should be developed.

Patterns and preferences of antidiabetic drug use in Turkish patients with type 2 diabetes - A nationwide cross-sectional study (TEMD treatment study).

AIMS: The treatment preferences in type 2 diabetes (T2DM) are affected by multiple factors. This survey aims to find out the profiles of the utilization of antidiabetics and their determinants. METHODS: The nationwide, multicenter TEMD survey consecutively enrolled patients with T2DM (n = 4678). Medications including oral antidiabetics (OAD) and injectable regimens were recorded. Multiple injectable regimens with or without OADs were defined as complex treatments. RESULTS: A total of 4678 patients with T2DM (mean age: 58.5 ± 10.4 years, 59% female) were enrolled. More than half of patients (n = 2372; 50.7%) were using injectable regimens with or without OADs, and others (n = 2306, 49.3%) were using only OADs. The most common OADs were metformin (93.5%), secretagogues (40.1%), and DPP-4 inhibitors (37.2%). The rates of the use of basal, basal-bolus and premix insulin were 26.5%, 39.5% and 22.4%, respectively. Patients using OADs achieved better glycemia, blood pressure and weight control (p < 0.001 for all) but poorer LDL-C control (p < 0.001). The independent associates of complex treatments were diabetes duration, obesity, eGFR, glycated haemoglobin, macro and microvascular complications, education level, and self-reported hypoglycemia. CONCLUSION: This study is the first nationwide report to show that almost half of the patients with T2DM are using injectable regimens in Turkey.

The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Early retinal neurodegeneration in preclinical diabetic retinopathy: a multifactorial investigation.

BACKGROUND/OBJECTIVES: To investigate effects of microalbuminuria (MA), diabetes duration, glycosylated haemoglobin (HbA1c) level, hypertension (HT) and/or hyperlipidaemia (HL) coexistence on retinal layers in diabetic patients without diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT). SUBJECTS/METHODS: This cross-sectional study involved 95 (45 had MA and 50 had no MA) patients with type 2 diabetes mellitus (DM) without DR and 91 age- and gender-matched non-diabetic controls. Macular and peripapillary SD-OCT measurements (Heidelberg Engineering GmbH, Heidelberg, Germany), DM duration, HbA1c levels and presence of HT and/or HL were used for statistical analyses. RESULTS: The MA (+), MA (-) and control groups had similar age and gender distribution (p > 0.05). The differences in SD-OCT measurements among the MA (+), MA (-) and control groups were insignificant (p > 0.05). However, diabetic patients (n = 95) had significantly thinner inferior-temporal peripapillary retinal nerve fibre layer (RNFL) (p = 0.042) than in the controls (n = 91). Superior peripapillary RNFL was significantly thinner in patients with an HbA1c level > 7% (p = 0.049). However, 3 mm-nasal, temporal and superior perifoveal thicknesses were significantly lower in patients with DM duration over 10 years (p < 0.05). HT and/or HL coexistence did not lead a significant difference in SD-OCT parameters among the groups. CONCLUSIONS: In diabetic patients without DR, peripapillary inferior-temporal RNFL thinning might be an early sign of neuroretinal degeneration and it seems to be independent from vascular endothelial damage (MA). Poor metabolic control appears to lead superior peripapillary RNFL thinning, while perifoveal thicknesses tend to decrease with longer DM duration.

Effect of microalbuminuria on corneal endothelium in patients with diabetes without retinopathy.

BACKGROUND: The aim of this study was to investigate the effect of microalbuminuria on corneal endothelium in patients with diabetes without retinopathy. METHODS: This cross-sectional study comprised 100 patients with type 2 diabetes mellitus (DM) without diabetic retinopathy and 92 control subjects without diabetes. Forty-five patients had microalbuminuria and 55 subjects were microalbuminuria negative. Endothelial measurements were obtained using specular microscopy. Endothelial cell density, average area, co-efficient of variation, maximum area, minimum area, hexagonality and corneal thickness were compared between the groups on the basis of microalbuminuria, DM duration and medication, HbA1c , body mass index, serum lipid and protein profiles, hypertension and hyperlipidaemia diagnosis. RESULTS: There were no significant differences in age, gender, endothelial cell density, average area, co-efficients of variation, maximum area, minimum area, hexagonality or corneal thickness among the microalbuminuria positive, microalbuminuria negative and control groups (p > 0.05). However, microalbuminuria positive patients had lower high-density lipoprotein levels than the microalbuminuria negative patients (p = 0.042). DM and control groups showed similar endothelial measurements (p > 0.05). Patients with a HbA1c > 7 per cent (53 mmol/mol) had lower hexagonality value (p = 0.039) than in the subjects with a HbA1c ≤ 7 per cent. No significant differences were found in endothelial parameters when groups were compared based on DM duration, medication and co-morbidities. CONCLUSIONS: Microalbuminuria positive and negative patients with DM without retinopathy seem to have similar corneal endothelial measurements with controls. However, patients with a HbA1c > 7 per cent should be monitored for deterioration in corneal endothelial cell morphology even without diabetic retinopathy, which might be critical prior to anterior segment surgery.

Osteocalcin and epicardial adipose tissue in obesity: new hints for epicardial adipose tissue-bone crosstalk.

Objectives: Osteocalcin (OC) appears to be involved in the regulation of glucose and fat metabolism. We aimed to determine the association between OC and epicardial adipose tissue (EAT) in premenopausal obese women. Design: The study included 73 premenopausal obese women and 55 non-obese women. Echocardiographic examination was performed to measure EAT. Serum OC levels were measured by chemiluminescence immunoassay. Results: OC levels were significantly lower in obese women than controls (18.26 ± 5.27 vs. 22.53 ± 6.84 ng/ml, p < .001). EAT thickness was higher in obese women than controls (5.19 ± 0.73 vs. 3.25 ± 1.35 mm, p < .001). In obese women, OC was positively correlated with EAT thickness (p = .043; r = 0.326). There was no correlation in controls. Conclusions: Premenopausal obese women had lower OC levels and thicker EAT than controls. There was a weak positive correlation between OC and EAT in premenopausal obese women. This potential cross talk between bone metabolism and EAT could play a role in the development of atherosclerosis in obesity.

Predictive power of different obesity measures for the presence of diastolic dysfunction.

OBJECTIVE: Body mass index (BMI) and waist circumference (WC) as measures of obesity have some limitations. The aim of this study was to evaluate whether one measure could predict the presence of diastolic dysfunction (DD) more accurately than the other measures. METHODS: A total of 91 obese patients without any other risk factors for DD were prospectively enrolled. Echocardiographic examination was performed. DD was defined and categorized according to recent guidelines. The study participants were divided into 2 groups according to the presence of DD. Weight, height, and WC were measured; BMI and waist-to-hip ratio (WHR) were calculated; and a body shape index (ABSI) was calculated as WC/(BMI2/3height1/2). The associations between ABSI, BMI, WHR, and WC and the presence of DD were examined using logistic regression analyses. Analysis of covariance was used to examine the differences. RESULTS: WC and BMI were significantly greater in subjects with DD (p=0.049 and 0.051, respectively). A greater BMI, WC, and WHR increased the risk of the presence of DD (BMIDD: odds ratio [OR]=1.096, p=0.024; WC-DD: OR=1.059, p=0.007; WHR-DD: OR=2.363, p=0.007). After adjustment for age and sex, only BMI continued to be significantly associated with DD (p=0.031). ABSI was not associated with DD. CONCLUSION: After adjustment for age and sex, BMI was the only predictor of DD in obesity. Despite its limitations, BMI may still be a potentially more accurate measure of DD compared with other obesity measures.

Serum leptin levels and GHR-d3/fl gene polymorphism in acromegalic patients with thyroid nodules.

BACKGROUND: Acromegaly is a rare and serious syndrome that is commonly associated with pituitary neoplasms. Thyroid multinodular disease is a common finding in acromegaly. Leptin is a polypeptide hormone, and studies have shown that it can increase cell proliferation and inhibit apoptosis. OBJECTIVES: The aim of the study was to determine the relationship of serum leptin levels with certain blood parameters and determine if growth hormone receptor (GHR)-d3/fl gene polymorphism is associated with thyroid nodules in acromegalic patients. MATERIAL AND METHODS: A total of 24 acromegalic patients with or without thyroid nodules were included in the study. Gene polymorphisms and blood parameters were examined. RESULTS: A marked increase was observed in serum leptin concentration in acromegalic patients with thyroid nodules compared to patients without them (p < 0.05). GH levels were lower in patients without nodules than in patients with nodules (p < 0.05). Blood glucose levels were higher in patients with nodules compared to those without them (p < 0.05), and the presence of thyroid nodules was associated with decreased blood low-density lipoprotein (LDL) levels compared to patients without nodules (p < 0.05). A significant relationship was observed between growth hormone receptor (GHR)-d3/fl gene polymorphism and leptin levels in acromegalic patients with thyroid nodules (p < 0.001). CONCLUSIONS: These data from acromegalic patients indicate that thyroid nodules are associated with increased serum leptin, GH and blood glucose levels and with decreased LDL levels. GHR-d3/fl gene polymorphism status was strongly related to higher leptin levels.

Clinical spectra of neuromuscular manifestations in patients with lipodystrophy: A multicenter study.

Lipodystrophy is a heterogeneous group of disorders characterized by loss of adipose tissue. Here, we report on clinical spectra of neuromuscular manifestations of Turkish patients with lipodystrophy. Seventy-four patients with lipodystrophy and 20 healthy controls were included. Peripheral sensorimotor neuropathy was a common finding (67.4%) in lipodystrophic patients with diabetes. Neuropathic foot ulcers were observed in 4 patients. Drop foot developed in 1 patient with congenital generalized lipodystrophy type 1. Muscle symptoms and hypertrophy were consistent findings in congenital generalized lipodystrophy (21/21) and familial partial lipodystrophy (25/34); on the other hand, overt myopathy with elevated creatine kinase activity was a distinctive characteristic of congenital generalized lipodystrophy type 4. Muscle biopsies revealed myopathic changes at different levels. Accumulation of triglycerides was observed which contributes to insulin resistance. All patients with congenital generalized lipodystrophy suffered from tight Achilles tendons at various levels. Scoliosis was observed in congenital generalized lipodystrophy type 4 (2/2) and familial partial lipodystrophy type 2 (2/17). Atlantoaxial instability was unique to congenital generalized lipodystrophy type 4 (2/2). Bone cysts were detected in congenital generalized lipodystrophy type 1 (7/10) and congenital generalized lipodystrophy type 2 (2/8). Our study suggests that lipodystrophies are associated with a wide spectrum of neuromuscular abnormalities.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION: We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Adiponectin and Cardiac Hypertrophy in Acromegaly.

BACKGROUND: Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. OBJECTIVES: The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. MATERIAL AND METHODS: We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. RESULTS: We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. CONCLUSIONS: Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be supported with other, wide, multi-centered studies.

The Association between Central Adiposity and Autonomic Dysfunction in Obesity.

OBJECTIVE: To determine the relationship between central adiposity parameters and autonomic nervous system (ANS) dysfunction. SUBJECTS AND METHODS: The study included 114 obese individuals without any cardiovascular risk factors. Weight (in kg), height (in m), and waist circumference (WC; in cm) were measured and body mass index was calculated. Echocardiographic examination was performed to measure left ventricular mass and epicardial fat thickness (EFT). All the participants underwent an exercise test and electrophysiological evaluation using electromyography. Heart rate recovery (HRR) at 1-5 min, R-R interval variation at rest and during hyperventilation, and sympathetic skin response were measured. Pearson's correlation analysis was used. Multiple linear regression analysis was used to identify the factors associated with autonomic dysfunction. RESULTS: The HRR at 1-5 min was negatively correlated with WC and age (WC-HRR1: r = -0.32; WC-HRR2: r = -0.31; WC-HRR3: r = -0.26; WC-HRR4: r = -0.23; WC-HRR5: r = -0.21; age-HRR2: r = -0.32; age-HRR3: r = -0.28; age-HRR4: r = -0.41; age-HRR5: r = -0.42). Age was the only independent predictor of reduced HRR at 1-5 min. In addition, WC predicted a reduced HRR at 3 min. There were no significant associations between central obesity and electrophysiological parameters. EFT was not associated with ANS dysfunction. CONCLUSION: In this study, central adiposity and aging were associated with ANS dysfunction in obese individuals. The WC could be a marker of ANS dysfunction in obese individuals without any cardiovascular risk factors. The HRR assessment at a later decay phase could be more valuable for evaluating ANS function than during early recovery.

Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells.

Exendin-4 is a GLP-1 analog used for the treatment of type 2 diabetes mellitus in its synthetic form. As women with diabetes have higher breast cancer incidence and mortality, we examined the effect of the incretin drug exendin-4 on breast cancer cells. The aim of the study is to investigate anticancer mechanism of exendin-4 in MCF-7 breast cancer cells. Cytotoxic effects of exendin-4 were determined by XTT assay. IC50 dose in MCF-7 cells were detected as 5 µM at 48th hour. Gene messenger RNA (mRNA) expressions were evaluated by real-time PCR. According to results, caspase-9, Akt, and MMP2 expression was reduced in dose group cells, compared with the control group cells. p53, caspase-3, caspase-8, caspase-10, BID, DR4, DR5, FADD, TRADD, PARP, PTEN, PUMA, NOXA, APAF, TIMP1, and TIMP2 expression was increased in dose group cells, compared with the control group cells. Effects of exendin-4 on cell invasion, colony formation, and cell migration were detected by Matrigel chamber, colony formation assay, and wound-healing assay, respectively. To conclude, it is thought that exendin-4 demonstrates anticarcinogenesis activity by effecting apoptosis, invasion, migration, and colony formation in MCF-7 cells. Exendin-4 may be a therapeutic agent for treatment of breast cancer as single or in combination with other agents. More detailed researches are required to define the pathways of GLP-1 effect on breast cancer cells because of the molecular biology of breast cancer that involves a complex network of interconnected signaling pathways that have role in cell growth, survival, and cell invasion.

Significance of IMP3, nucleophosmin, and Ki-67 expression in papillary thyroid carcinoma.

The purpose of our study was to investigate the diagnostic value of expression of IMP3, nucleophosmin, and correlation of these markers with Ki-67 proliferation index in papillary thyroid carcinoma and benign neoplasms of thyroid gland. The aim was also to investigate whether there is a difference between papillary and micropapillary carcinomas with regard to clinicopathologic parameters beside IMP3, nucleophosmin, and Ki-67 proliferation index. It was concluded that IMP3 and nucleophosmin cannot be a routine diagnostic marker for discrimination of papillary carcinomas and benign lesions. IMP3 positive staining was quite scarce in IMP3 positive papillary carcinomas although specifity of IMP3 is 100%. A statistically significant correlation was not detected between nucleophosmin, IMP-3, and Ki-67 proliferation index. A statistically significant correlation was found between tumor size, lymphovascular embolism, and Ki-67 proliferation index. There was also significant correlation between tumor size and lymphovascular embolism.

Resistin and leptin levels in acromegaly: lack of correlation with echocardiographic findings.

PURPOSE: To find out how resistin and leptin levels were affected in patients with acromegaly and whether there is a relation between resistin levels and cardiac parameters. We also aimed to investigate whether resistin and leptin may be a link between insulin resistance and cardiac functions as well as these affected cardiac functions in the patients with acromegaly. METHODS: We included 30 subjects (15 men and 15 women) who had a diagnosis of acromegaly and 30 healthy (10 men and 20 women) subjects. Serum glucose, insulin, growth hormone, insulinlike growth factor 1 (IGF-1), resistin, and leptin levels were obtained, and insulin resistance of subjects were calculated. Echocardiographic studies of the subjects were performed. RESULTS: Resistin levels of the patients with acromegaly were found lower than controls. This difference was statistically significant (P = 0.001). Leptin levels were lower in the patients with acromegaly than in the controls, but this difference was not statistically significant. Resistin and leptin levels were not correlated with growth hormone, IGF-1, and with insulin-like growth factor binding protein 3 levels. Homeostasis model assessment of insulin resistance was positively correlated with resistin levels. (P = 0.03; r = 0.531) but not correlated with leptin levels. There was a positive correlation between body mass index and leptin levels in the patients with acromegaly (P = 0.007; r = 0.482). Interventricular septum thickness, posterior wall thickness, left ventricle mass index, peak early mitral inflow velocity-peak late mitral inflow velocity ratio, deceleration time, ejection time, isovolumetric relaxation time, velocity propagation, and left ventricular end-systolic volume values were significantly greater in the patients with acromegaly. Leptin levels in the acromegalic patients were not correlated with any of them. CONCLUSIONS: We found biventricular hypertrophy and impairment of diastolic and systolic function in the patients with acromegaly. We conclude that changes in resistin and leptin levels are unlikely to account for the insulin resistance of acromegaly. They do not also seem to be contributing factors of cardiovascular changes in patients with acromegaly.

Evaluation of body fat distribution in PCOS and its association with carotid atherosclerosis and insulin resistance.

OBJECTIVE: The aim of this study was to compare body fat distribution in PCOS with healthy controls and to investigate the factors associated with carotid artery intima media thickness (IMT) and insulin resistance. SUBJECTS AND METHODS: A case control study was conducted in 46 women with PCOS and 43 age matched controls. Anthropometrical measurements, hormonal levels, lipid and glucose profile were evaluated. Body fat thickness in four regions and carotid IMT were measured. Body fat distribution was compared between groups. Correlation of these parameters with carotid artery IMT and insulin resistance was investigated. RESULT(S): Visceral and subcutaneous fat thickness and the mean carotid artery IMT were significantly higher in PCOS subjects (p < 0.01). In correlation analysis, age, body mass index (BMI) and waist hip ratio (WHR) showed correlation with carotid artery IMT (r = 0,55, p < 0,001; r = 0.41, p < 0.008 and r = 0.34 p = 0.03, respectively), whereas visceral fat thickness presented a correlation with HOMA-IR index as a sign of insulin resistance. CONCLUSION(S): Fat accumulation is more prominent in visceral and subcutaneous regions in PCOS. Increased BMI and abdominal type of obesity are closely related to the increased carotid artery IMT and insulin resistance. Weight control and regional weight loss are important part of the treatment for the future health of women with PCOS.