Relationship between serum Betatrophin, GPIHBP1, and LDL subfractions in patients with gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) leads to changes in the lipid metabolism. In this study, we aimed to compare serum levels of LDL subfractions, betatrophin, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) between patients with GDM and healthy pregnant women. DESIGN AND METHODS: We designed a prospective case-control study with 41 pregnant women. Subjects were divided into two groups: GDM and control. Betatrophin and GPIHBP1 levels were measured by ELISA method. Lipoprint LDL subfraction kit was used to perform LDL subfraction analysis electrophoretically. RESULTS: Serum levels of LDL6 subfraction, betatrophin, and GPIHBP1 were found to be higher in GDM group compared to the controls (p < 0.001). The mean LDL size were also found larger in GDM group. A positive correlation was found between betatrophin and GPIHBP1 levels (rho = 0.96, p < 0.001). CONCLUSIONS: Our findings suggest that betatrophin, and GPIHBP1 levels were found to be increased in GDM. This maybe the result of adaptive mechanisms in response to insulin resistance, but also this relationship should be evaluated for their effects on impaired lipid metabolism and lipoprotein lipase metabolism. There is a need for further prospective studies with larger samples to fully elucidate the mechanisms of this relationship both in pregnant patients and the other patient groups.

Increased Endothelial Dysfunction and Insulin Resistance in Patients with Klinefelter Syndrome.

BACKGROUND AND OBJECTIVE: Patients with Klinefelter Syndrome (KS) have increased cardiometabolic risk however the pathogenesis is not clear. We investigated the presence of endothelial dysfunction, insulin resistance and inflammation in an unconfounded population of KS. METHODS: A total of 32 patients with KS (mean age 21.59 ± 1.66 years) and 33 healthy control subjects (mean age: 22.15 ± 1.03 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), homeostatic model assessment of insulin resistance (HOMA-IR) index and highsensitivity C-reactive protein (hs-CRP) levels were measured. RESULTS: The patients had higher Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), insulin, HOMA-IR and ADMA levels (p < 0.001 for all) and lower High Density Lipoprotein Cholesterol (HDL-C) and total testosterone levels (p=0.002 and p<0.001, respectively), compared to the healthy controls. Total testosterone levels were significantly negatively correlated to ADMA (r = - 0.479, p < 0,001), hs-CRP (r = -0.291, p = 0.034) and positively correlated to HDL-C (r = 0.429, p = 0.001) levels. The multivariate analysis has shown that total testosterone (ß = -0.412, p = 0.001) and TG (ß = 0.332, p = 0.009) levels were the significant independent determinants of the plasma ADMA levels. CONCLUSION: The results of the present study show that endothelial dysfunction and insulin resistance are prevalent even in the very young subjects with KS, who have no metabolic or cardiac problems at present. Also, hypogonadism seems to play an important role for increased cardiometabolic risk in patients with KS.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism

ABSTRACT Background Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. Subjects and methods A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. Results The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = −0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = −0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. Conclusions The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism.

BACKGROUND: Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. SUBJECTS AND METHODS: A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. RESULTS: The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = -0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = -0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. CONCLUSIONS: The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Effect of testosterone replacement therapy on vitamin D and FGF-23 levels in congenital hypogonadism.

INTRODUCTION: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. MATERIAL AND METHODS: Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. RESULTS: After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p<0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006). CONCLUSIONS: The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.

Add on Exenatide Treatment is Beneficial in Poorly Controlled Obese Type 2 Diabetics under Intensive Insulin Regimens.

Background: Intensive insulin treatment is bothersome in obese patients with type 2 diabetes mellitus. High insulin dosages further increase weight gain and the risk of hypoglycemia. Glucagon like peptide-1 receptor agonists decrease the insulin need, cause weight loss and reduce the risk of hypoglycemia. There is limited data about the effect of exenatide on obese diabetics under intensive insulin regimens. Methods: This retrospective case series report the clinical outcomes of 23 obese (13 morbidly obese) patients with uncontrolled type 2 diabetes mellitus (Age=59±10.44 years, body mass index 41.1±6.8 kg/m2, HbA1c 9.9±1.5%), under high dose (94.1±39.6 unit) intensive insulin. Exenatide twice daily was added for a mean follow-up period of 11.22±7.01 (3-30) months. Intensive insulin regimens were continued in 7 patients while the others were switched to basal insulin during the follow-up. Results: During the follow-up, mean HbA1c levels of the patients significantly improved (p=0.019), along with the significant decrease in body mass index and the total insulin need (p<0.001 for both). Baseline insulin dosages were significantly higher in the intensive regimen group (p=0.013) while other demographical and clinical characteristics were similar. No significant difference was present between the groups regarding the alterations of HbA1c, body mass index and the reduction in total insulin dosages. Conclusion: Add on exenatide appears to be a rational treatment modality in uncontrolled obese patients with type 2 diabetes mellitus despite intensive insulin regimens. Further prospective randomized studies with longer follow-up periods are recommended.

Endothelial dysfunction, insulin resistance and inflammation in congenital hypogonadism, and the effect of testosterone replacement.

Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p<0.001 for all) and lower TWEAK levels (p<0.001), compared to the healthy controls. After 5.56 ± 2.04 months of TRT, the patients had significantly elevated systolic blood pressures (p=0.01), body mass indexes and WC (p<0.001 and p=0.001 respectively) and decreased total and HDL cholesterol levels (p=0.032 and p<0.001 respectively). ADMA levels significantly increased (p=0.003), while the alterations in TWEAK, hsCRP and HOMA-IR were not significant. The results of the present study show that endothelial dysfunction, inflammation and insulin resistance are prevalent even in the very young subjects with CHH, who have no metabolic or cardiac problems at present. This increased cardiometabolic risk however, do not improve but even get worse after six months of TRT. Long term follow-up studies are warranted to investigate the unfavorable cardiometabolic effects of TRT.

Effects of androgen replacement therapy on cornea and tear function in men with idiopathic hypogonadotropic hypogonadism.

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) is an endocrine disorder defined with the presence of typical clinical signs and symptoms plus laboratory confirmation of serum testosterone (T) levels lower than 300 ng/dl. Androgen replacement therapy (ART) is the first-step treatment of male IHH. To date, no clinical trial, which investigates the changes on corneal structure and tear function, of systemic ART in men have been published. The objective of this study was to investigate the effects of ART on cornea and tear function in patients with IHH. MATERIALS AND METHODS: This prospective, interventional study was conducted at the Gulhane Military Medical Academy, Ankara, Turkey, a tertiary referral military hospital. Thirty-four eyes of 17 men with IHH patients were evaluated with Schirmer I test, ultrasound pachymeter, applanation tonometer and confocal microscopy. A Testosterone compound (Sustanon® 250 mg) was administered by intramuscular injection in the course of a 3-week period to induce puberty, and human chorionic gonadotropin (Pregnyl® 5000 IU) was administered twice weekly for 3 months to induce fertility. The patients were re-evaluated at the third month of the treatment. Main Outcome Measures were Schirmer score, central corneal thickness (CCT), intraocular pressure (IOP), endothelial cell density, coefficient of variation and cell shape. RESULTS: Schirmer scores showed similar results after the treatment compared to pre-treatment levels (p = 0.14). There was no statistically significant difference in CCT and IOP compared to baseline data (p = 0.96, p = 0.73, respectively), and no significant differences were found in corneal endothelial cell density, percentage of cell size variability or hexagonality (p = 0.83, p = 0.58, p = 0.64, respectively). CONCLUSIONS: This is the first study that investigates the effects of ART on corneal structure and tear function in men. ART seems to have no short-term effects on corneal structure and tear function. Further publications of larger, long-term and controlled studies are needed.

[Multiplex ligation dependent probe amplification analysis of KAL1, GNRH1, GNRHR, PROK2 and PROKR2 in male patients with idiopathic hypogonadotropic hypogonadism].

INTRODUCTION: The purpose of this study was to determine the prevalence of KAL1, GNRH1, GNRHR, PROK2, and PROKR2 copy numbervariations in patients with idiopathic hypogonadotropic hypogonadism (IHH). MATERIAL AND METHODS: 86 hypogonadal males (76 diagnosed with normosmic idiopathic hypogonadotropic hypogonadism [nIHH] andten with Kallmann syndrome [KS]) and 95 healthy control individuals were studied for the presence of aforementioned genomic rearrangements,using multiplex ligation dependent probe amplification (MLPA). RESULTS: We detected that of the 86 patients, three with KS had a deletion of the KAL1 gene in exon 9, one of whom also carried a duplicationin exon 11; and three with nIHH had a duplication of the PROK2 gene in exon 3; a deletion of the GNRHR gene in exon 1; anda duplication of the same gene in exon 2, respectively. No abnormalities were found in the patient group for the PROKR2 and GNRH1genes. In addition, no genomic rearrangements were identified in the healthy control individuals for the described genes. CONCLUSIONS: Defining the genetic basis of disease is essential to improve our understanding of this complex disorder, and could be usefulfor genetic counselling and for directing therapy. In addition, discovering the association between genetic mutations and disease isimportant for our better understanding of normal reproductive functions.

Increased frequency of anxiety, depression, quality of life and sexual life in young hypogonadotropic hypogonadal males and impacts of testosterone replacement therapy on these conditions.

Hypogonadotropic hypogonadism is defined as the failure in production of gonadal hormones, thus resulting in lower amounts of testosterone. Depression, anxiety and decreased quality of life are the most common psychopathological conditions in young hypogonadal men. The aim of the present study was to assess the still debated relationship with testosterone levels and psychological symptoms in young male patients with congenital hypogonadotropic hypogonadism (CHH). Thirty-nine young male patients with CHH and 40 age-matched healthy males were enrolled in the present study. The impact of testosterone replacement treatment (TRT) on the patients' anxiety and depression levels, sexual function and quality of life were assessed before and after 6 months of treatment using valid and reliable scales, including the Short Form-36 (SF-36), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Arizona Sexual Experiences (ASEX). Patients with CHH had significantly higher scores for BDI, BAI, and ASEX than the control subjects at baseline (p=0.011, p=0.036, p<0.001, respectively). The ASEX and BDI scores significantly improved after the TRT (p<0.001 for both), while the improvement in the BAI score was not statistically significant (p=0.135). When compared to the control group, treatment naïve hypogonadal patients had more severe symptoms of sexual dysfunction, anxiety, depression, and worse quality of life. After 6 months of TRT, we observed improvements in the above parameters, suggesting that low endogenous levels of testosterone might be related to the increased incidence of psychological symptoms.

High plasma level of long Pentraxin 3 is associated with insulin resistance in women with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS. MATERIALS AND METHODS: Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. RESULTS: Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p = 0.021, p = 0.002 and p = 0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist-to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p < 0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p < 0.05, for all). CONCLUSION: PTX3 level is increased in patients with PCOS in concordance with insulin resistance.

The relationship between ghrelin levels and insulin resistance in men with idiopathic hypogonadotrophic hypogonadism at diagnosis and after therapy.

INTRODUCTION: It has recently been shown that ghrelin affects energy balance and reproductive function, but the role of ghrelin in the pathogenesis of insulin resistance is unclear. Firstly to assess the interaction between insulin resistance and ghrelin levels in hypogonadal men, and then to show the effects of testosterone (T) therapy on insulin and ghrelin. MATERIAL AND METHODS: Twenty-four male patients newly diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) and 20 healthy male subjects were enrolled in this study. Ghrelin, insulin, glucose, total and free testosterone levels, HOMA-IR and QUICKI, and percentage of body fat mass were determined at baseline in all subjects and after therapy in hypogonadal men. RESULTS: When compared with control subjects, hypogonadal men had significantly lower total and free T concentrations, ghrelin levels, and QUICKI whereas they had significantly higher body fat mass and HOMA-IR score. Following T therapy, a significant increase in ghrelin and QUICKI, and a decrease in HOMA-IR score and body fat mass were demonstrated in hypogonadal men. Calculation of the Pearson coefficient showed that ghrelin concentrations in hypogonadal men were positively correlated with free and total testosterone and QUICKI, whereas they were negatively correlated with body fat mass and HOMA-IR. After six months of T therapy, these correlations were still observed. CONCLUSIONS: Our data supports the notion that ghrelin may constitute an important link between the regulation of reproduction and metabolic homeostasis.

A multicentric, hyaline vascular variant of Castleman's disease associated with B cell lymphoma: a case report.

INTRODUCTION: Three histological variants (hyaline vascular, plasma cell, and mixed) and two clinical types (localized and multicentric) of Castleman's disease have been described. The risk of progression to lymphoma is higher in multicentric Castleman's disease and is associated with poorer outcomes and higher mortality rate. Multicentric Castleman's disease often requires systemic therapy. Complete resection of the involved node in localized Castleman's disease is curative, with no reported recurrences. CASE PRESENTATION: We report a case of a 66-year-old female with systemic symptoms and bilateral cervical lymph nodes which were initially diagnosed as the hyaline vascular variant of Castleman's disease and two years later after the initial diagnosis she was confirmed to B cell lymphoma. Following the treatment with radiation therapy to the cervical area and combination chemotherapy complete response was achieved. CONCLUSION: Although it has rarely been reported, the malignant potential of the Castleman's disease must be kept in mind.

A rare initial manifestation of acute lymphocytic leukemia: bilaterally enlarged kidneys and liver.

A case with early presentation of acute lymphocytic leukemia with bilaterally enlarged kidneys and liver is presented. Both hepatic and renal infiltration with leukemic cells is a rare manifestation of acute lymphocytic leukemia.

Clinicopathologic characteristics and therapeutic outcomes of primary gastrointestinal non-Hodgkin's lymphomas: 10 years of experience from a single center in eastern Anatolia.

OBJECTIVE: The objective of this retrospective study was to report the clinicopathological data and the treatment outcomes in patients with primary gastrointestinal non-Hodgkin's lymphoma. PATIENTS AND METHODS: We carried out a retrospective analysis of 41 patients (22 females, 18 males, median age 58 and range 18-90 years) who presented to our department with histopathological diagnosis of primary gastrointestinal non-Hodgkin's lymphoma between 1995 and 2004. RESULTS: The stomach was the most common extranodal site and was seen in 25 of 41 (61%) patients. At presentation 28 (68.3%) patients had gastrointestinal symptoms while 27 (65.9%) had B symptoms. The range of follow-up was 2-84 months with a median of 9 months. The overall survival rate was 3 years for 25 (61.2%) patients. The 3-year overall survival rate was better in patients with early-stage disease (stages I and II(1)) who were treated with surgery plus chemotherapy and/or radiation therapy than in those treated with chemotherapy alone (91.6 vs. 50%, p < 0.05). The disease had a significant impact on both the progression-free survival and overall survival rates. CONCLUSION: Our data showed that surgical resection prior to postoperative chemotherapy was a better option for patients with early-stage disease with better patient survival.

Nodular melanoma presenting with rapid progression and widespread metastases: a case report.

INTRODUCTION: Melanoma is responsible for 1% to 2% of all cancer deaths around the world. Nodular melanoma often carries a poor prognosis because of no prodromal radial growth phase, early distant metastasis and significant tumor volume. CASE PRESENTATION: We present a case of progressive melanoma. A 51-year-old man was admitted to our hospital with dyspnea and skin lesions. These were multiple, dark colored, firm, and nodular and varied in size. He was diagnosed with melanoma. Temozolomide was administered, but he died of respiratory failure within a week after diagnosis. CONCLUSION: Nodular melanoma tends to spread rapidly and eventually metastasize to vital organs. It may be fatal within months of recognition.