Betatrophin Levels Are Related to the Early Histological Findings in Nonalcoholic Fatty Liver Disease.

Betatrophin, a liver hormone, regulates glucose and lipid metabolism. We investigated the betatrophin levels in nonalcoholic fatty liver disease (NAFLD) and searched for any relationship with histological severity and metabolic parameters. Fifty males with NAFLD [Nonalcoholic Steatohepatitis (NASH) (n = 32); non-NASH (n = 18)] and 30 healthy controls were included. Plasma betatrophin was measured by ELISA method. Insulin sensitivity was assessed by HOMA-IR index. Histological features were scored by the semi quantitative classification and combined as the NAFLD activity score (NAS). Betatrophin levels in the non-NASH group were significantly higher than the controls. Betatrophin was positively correlated to the age, waist circumference, total cholesterol, triglycerides, LDL cholesterol, glucose, insulin, HOMA-IR index and gamma glutamyl transpeptidase levels, and negatively correlated to the steatosis and NAS. In the stepwise linear regression analysis, the triglyceride (ß = 0.457, p < 0.001), glucose (ß = 0.281, p = 0.02) and NAS (ß = -0.260, p = 0.03) were the independent determinants of betatrophin. Betatrophin levels are higher in the early stages of NAFLD and tend to decrease when the disease progresses. This could be an important preliminary mechanistic finding to explain the increased frequency of glucose intolerance during the course of NAFLD.

Elevated plasma asymmetric dimethylarginine levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction.

OBJECTIVES: Beta-thalassemia major is associated with the increased risk of cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) has been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. In this study, we aimed to investigate circulating ADMA concentrations in children with beta-thalassemia major. METHODS: Thirty-one beta-thalassemia major children aged between 4 and 16 year old and age, gender-matched 36 healthy controls were enrolled in the study. Plasma ADMA was measured along with the soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), P-selectin, and Pentraxin-3. RESULTS: Age, gender and body mass index were similar in two groups. Plasma ADMA, sVCAM-1, and sICAM-1 measurements were significantly higher in beta-thalassemia major patients than the control group (p < 0.004 for ICAM-1, p < 0.001 for other parameters). There were positive significant correlations between ADMA, sVCAM-1 and sICAM-1 (r = 0.437, p < 0.001; r = 0.544, p < 0.001; r = 0.405, p < 0.001, respectively) in the whole group. DISCUSSION: The findings of the current study show us that increased plasma ADMA levels in children with beta-thalassemia major may be an early marker for endothelial dysfunction and may play a role in the development of premature atherosclerosis in beta-thalassemia major patients.

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.

Assessment of the role of serum ischemia-modified albumin in obstructive sleep apnea in comparison with interleukin-6.

OBJECTIVES: There is limited and contradictory information regarding the role of serum ischemia-modified albumin (IMA) in obstructive sleep apnea (OSA). In this study we examine the effects of OSA and obesity on IMA and interleukin-6 (IL-6), and detect whether IMA and IL-6 may be potential biomarkers in OSA. METHODS: Fifty-one males who underwent all night polysomnography test were included into the study. Body-mass index (BMI) and apnea-hypopnea index (AHI) of all patients were determined. Serum IMA and IL-6 levels, erythrocyte sedimentation rate (ESR), complete blood count, routine blood biochemistry and thyroid function tests were performed. RESULTS: Mean IMA [0.36 (± 0.04) U/ml, 0.89 (± 0.15) U/ml], mean IL-6 [1.01 (± 0.19) pg/ml, 2.02 (± 1.19) pg/ml] and mean ESR [4.14 (± 2.5) mm/h, 14.35 (± 13.7) mm/h] levels showed significant difference between non-OSA and OSA groups (P = 0.005, P < 0.001, P < 0.001, respectively). Sensitivity of IMA in distinction of non-OSA/OSA was equal to IL-6 and higher than ESR. IMA was also a stronger predictive factor than IL-6 and ESR in the evaluation of OSA groups (severe/mild/moderate OSA and non-OSA). IMA was the sole distinctive biomarker in assessment of obese and non-obese cases. IMA correlated with IL-6, AHI and ESR. CONCLUSION: Serum IMA may be a valuable oxidative stress indicator for OSA and could act as a better biomarker than IL-6 for reflecting the presence and the severity of OSA.

The role of urinary nerve growth factor for the diagnosis and assessment of the biofeedback success in children with dysfunctional voiding.

INTRODUCTION: Dysfunctional voiding (DV) occurs in neurologically normal children who are not able to establish brain control on detrusor muscle contractions (DMCs). It is also reported to be the result of incorrect voiding habits during toilet training. Children contract pelvic floor muscles (PFMs) to suppress DMC and DV begins. Urinary nerve growth factor (uNGF) is necessary for the synthesis and regulation of neurotransmitters, development of dorsal root ganglia (sensory neurons), and development of sympathetic cells during embryonic and post-natal life. uNGF has also a role in the intracellular signal transduction in nerve cells towards the target organ. To our knowledge, no study has investigated the association between uNGF, biofeedback treatment and DV in children. OBJECTIVES: The aim was to examine the potential effect of uNGF in the assessment of the effectiveness of biofeedback success in children with lower urinary tract disorders. STUDY DESIGN: Fifty-two children with the suspicion of DV and 48 children from a primary school reporting no urinary complaints were enrolled in this study from October 2010 to April 2013 in the Urology Department. uNGF levels were compared. RESULTS: The mean uNGF/creatinine (Cr) level was 0.23 ± 0.26 in the control group and 0.96 ± 0.88 in the DV group (p < 0.001). The mean uNGF/Cr levels in the DV group at baseline and at the end of biofeedback therapy at 6 and 12 months were 0.90 ± 0.78, 0.26 ± 0.32, and 0.40 ± 0.50, respectively (p < 0.001) (Figure). DISCUSSION: To our knowledge this study is the first to show the correlations between uNGF levels and biofeedback therapy in children with DV. Tissue NGF in 12 patients with overactive bladder (OAB)/detrusor overactivity and 15 healthy women was previously compared and it was suggested that there was no correlation between bladder tissue NGF and OAB. uNGF levels in the bladder in patients with interstitial cystitis and idiopathic sensorial urgency were evaluated previously, and uNGF levels reported. Similar to these reports, most of the previous studies handled uNGF in patients with diseases such as interstitial cystitis, OAB, urinary tract infections, urolithiasis, spinal cord injury, and prostate cancer, and found significantly higher uNGF levels. These studies were generally in adults. A previous study about uNGF comprised 40 children with OAB, in contrast to other studies. According to this study, 40 children diagnosed with OAB were administered anti-muscarinic therapy (oxybutynin 0.3-0.5 mg/kg/day). It was reported that uNGF/Cr levels of the OAB group were higher than control group. In the current study, we evaluated the uNGF difference in DV and the effect of biofeedback treatment on uNGF levels. CONCLUSIONS: uNGF levels were higher in children with DV and decreased after biofeedback therapy. uNGF levels could be used for the diagnosis and the assessment of biofeedback success in these children.

Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey.

OBJECTIVE: Transfusion of platelet suspensions is an essential part of patient care for certain clinical indications. In this pioneering study in Turkey, we aimed to assess the in vitro hemostatic functions of platelets after cryopreservation. MATERIALS AND METHODS: Seven units of platelet concentrates were obtained by apheresis. Each apheresis platelet concentrate (APC) was divided into 2 equal volumes and frozen with 6% dimethyl sulfoxide (DMSO). The 14 frozen units of APCs were kept at -80 °C for 1 day. APCs were thawed at 37 °C and diluted either with autologous plasma or 0.9% NaCl. The volume and residual numbers of leukocytes and platelets were tested in both before-freezing and post-thawing periods. Aggregation and thrombin generation tests were used to analyze the in vitro hemostatic functions of platelets. Flow-cytometric analysis was used to assess the presence of frozen treated platelets and their viability. RESULTS: The residual number of leukocytes in both dilution groups was <1x106. The mean platelet recovery rate in the plasma-diluted group (88.1±9.5%) was higher than that in the 0.9% NaCl-diluted group (63±10%). These results were compatible with the European Directorate for the Quality of Medicines quality criteria. Expectedly, there was no aggregation response to platelet aggregation test. The mean thrombin generation potential of post-thaw APCs was higher in the plasma-diluted group (2411 nmol/L per minute) when compared to both the 0.9% NaCl-diluted group (1913 nmol/L per minute) and the before-freezing period (1681 nmol/L per minute). The flow-cytometric analysis results for the viability of APCs after cryopreservation were 94.9% and 96.6% in the plasma and 0.9% NaCl groups, respectively. CONCLUSION: Cryopreservation of platelets with 6% DMSO and storage at -80 °C increases their shelf life from 7 days to 2 years. Besides the increase in hemostatic functions of platelets, the cryopreservation process also does not affect their viability rates.

In vitro efficacy of frozen erythrocytes: implementation of new strategic blood stores to alleviate resource shortage (issue revisited).

BACKGROUND/AIM: Currently, the provision of blood products largely depends on walking blood banks and limited amounts of stored blood with short shelf lives. We aimed to compare the efficacy of erythrocyte concentrate (ECs) by pre- and postfreezing in vitro tests. MATERIALS AND METHODS: In our study, 10 ECs were glycerolized, frozen, thawed, and then deglycerolized using the Naval Blood Research Laboratory method. In addition to using the standard tests, ATP and 2,3-DPG levels and the viability of erythrocytes were also determined. RESULTS: The prefreezing mean viability rates of erythrocytes changed from 89.7 ± 13.7% to 98.6 ± 1.8% after thawing and deglycerolization. Prefreezing and day 0 ATP levels (1.64 ± 0.15 µmol/g Hb and 1.81 ± 0.14 µmol/g Hb, respectively) were similar. The 2,3-DPG levels decreased from 18.09 ± 4.78 µmol/g Hb measured before the procedure to 10.41 ± 4.58 µmol/g Hb on day 0. The mean hemolysis rates and supernatant Hb levels changed from 0.21 ± 0.11% to 0.36 ± 0.12% and 1 ± 0.5 g/L to 1.5 ± 0.5 g/L, respectively. CONCLUSION: The test results showed the efficacy of the frozen-thawed ECs to be used in humans for a broad spectrum of clinical indications. As a part of a contingency plan, national frozen blood reserves need to be established.

Low- and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiometabolic risk. Although dyslipidemia represents a key factor in this disease, its impact on serum levels of distinct lipoprotein subfractions is largely unknown. OBJECTIVE: To assess the full low-density lipoprotein (LDL) and high-density lipoprotein (HDL) profiles in patients with NAFLD. METHODS: Seven LDL and 10 HDL subfractions were assessed by gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA) in men with biopsy proven NAFLD (simple steatosis [n = 17, age, 34 ± 7 years] and nonalcoholic steatohepatitis [NASH; n = 24, age, 32 ± 6 years]). Exclusion criteria included robust alcohol consumption, infection with hepatitis B or C virus, body mass index ≥ 40 kg/m(2), diabetes mellitus, and hypertension. RESULTS: Compared with simple steatosis, NASH patients had similar body mass index, homeostasis model assessment of insulin resistance index and plasma lipids, with increased levels of both aspartate aminotransferase and alanine transaminase. NASH subjects had lower levels of larger LDL1 (10 ± 4 vs 13 ± 4%, P = .010) and increased smaller LDL3 and LDL4 particles (9 ± 5 vs 5 ± 5%, P = .017 and 3 ± 3 vs 1 ± 2%, P = .012, respectively). No changes were found in the HDL subclass profile. By multiple regression analysis, we found that NASH was associated only with increased levels of LDL3 (P = .0470). CONCLUSIONS: The increased levels of small, dense LDL3 and LDL4 in NASH may help to at least partly explain the increased risk for atherosclerosis and cardiovascular diseases in these patients.

Paraoxonase 1 Activity and Survival in Sepsis Patients.

BACKGROUND: Sepsis is a state of augmented oxidative stress and diminished antioxidant capacity. High density lipoprotein (HDL) particles were shown to possess antioxidant and anti-inflammatory properties, as well as Paraoxonase 1 (PON1), which is an enzyme that is also protective against HDL oxidation. Previous studies suggested a possible role of decreased PON1 activity or HDL levels in sepsis patients. AIMS: The present study was designed to test a hypothesis that higher PON1 activity and HDL-cholesterol levels could predict a better survival in sepsis patients. STUDY DESIGN: Observational study. METHODS: Venous blood samples were collected from sepsis patients for HDL-cholesterol levels, PON1 activity and cytokine assays (TNF-α and IL-6) and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores were calculated in order to weight patients' disease severity on the day of sepsis diagnosis. Patients were followed-up until the 28(th) day for any cause intra-hospital mortality. Data were statistically analyzed for effects of study parameters on patients' survival. RESULTS: In total, 85 patients with sepsis were included in the study. The mean age was 65.2±17.9 years and 48 were male; at the end of the 28-day follow-up period, 46 survived. TNF-α (86.9±10.5 vs 118.6±16.4) and IL-6 levels (906.7±82.7 vs 1323.1±54.3) were significantly higher in non-survivors, while PON1 activity (140.7±42.3 vs 66.7±46.6) and HDL-cholesterol levels (43.6±8.1 vs 34.5±8.9) were significantly higher in survivors (p<0.001 for all). TNF-α (r=-0.763) and IL-6 levels (r=-0.947) showed strong negative correlations, PON1 activity (r=0.644) and HDL-cholesterol levels (r=0.477) showed positive correlations with patient survival (p<0.001 for all). Survival estimates significantly favored TNF-α (Log Rank 59.5, p<0.001) and IL-6 levels (Log Rank 53.2, p<0.001) according to PON1 activity (Log Rank 5.4, p<0.03) and HDL-cholesterol levels (Log Rank 8.3, p<0.005). Regression analyses for relative contributions of parameters to survival showed that higher IL-6 levels (t: -16.489, p<0.001) were the most significant negative factor for survival, and TNF-α levels (t: -4.417, p<0.001), whereas PON1 activity had a positive effect (t:3.210, p<0.003). CONCLUSION: The present study showed that although low PON1 activity and HDL-cholesterol levels were related to mortality, higher levels were not found to be as predictive as cytokine levels for survival.

Body mass index and ghrelin levels after laparoscopic Nissen fundoplication.

PURPOSE: The study aims to evaluate the changes between body mass index (BMI) and ghrelin levels after laparoscopic Nissen fundoplication (LNF). METHODS: Twenty-four consecutive patients with gastroesophageal reflux disease who were scheduled for LNF consented to participate in the study. The participants' age, sex, preoperative (phase 0), postoperative 1st week (phase 1) and postoperative 4th week (phase 2) dysphagia scores, plasma ghrelin levels, and BMI were recorded. RESULTS: Compared to the preoperative level (phase 0), ghrelin was decreased in both phase 1 and phase 2. A strong correlation in the changes in the ghrelin values and BMI between phase 0 and phase 2 was detected. There was a strong, statistically significant difference in the changes in the BMI values between phase 1 and phase 2. CONCLUSIONS: Total plication of the fundus impairs its ghrelin-secreting functions for up to 4 weeks and is accompanied by weight loss.

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.

The relationship of circulating fetuin-a with liver histology and biomarkers of systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Fetuin-A, a glycoprotein with anti-inflammatory properties, plays an important role in counter-regulating inflammatory responses. It has also been associated with insulin resistance and metabolic syndrome. We aimed to investigate circulating concentrations of fetuin-A and its possible association with hepatic and systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: We included 105 nondiabetic male subjects with NAFLD [nonalcoholic steatohepatitis (NASH, n = 86) and simple steatosis (SS, n = 19)]. Plasma levels of fetuin-A and markers of inflammation [high-sensitive C reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and adiponectin] were measured by enzyme-linked immunosorbent assay method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. RESULTS: Fetuin-A was negatively correlated with age (r = -0.27, P = 0.006), however there was no association between fetuin-A and body mass index, waist circumference (WC), glucose, insulin, HOMA-IR, lipid parameters, and inflammatory markers. In addition, no significant association was observed between fetuin-A and histological findings including liver fibrosis. CONCLUSION: This study demonstrated that plasma fetuin-A levels are not correlated with the hepatic histology and systemic markers of inflammation in nondiabetic subjects with NAFLD. Our data also suggested that age is significantly associated with fetuin-A in this clinically relevant condition.

Insulin Resistance but Not Visceral Adiposity Index Is Associated with Liver Fibrosis in Nondiabetic Subjects with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes mellitus, and dyslipidemia. It is well known that the presence of visceral fat increases the risk for metabolic complications of obesity, especially NAFLD. The visceral adiposity index (VAI), a novel marker of visceral fat dysfunction, shows a strong association with insulin resistance and also cardiovascular and cerebrovascular events. However, there is conflicting data regarding the association between VAI and NAFLD. Our aim was to assess the relationship between VAI, insulin resistance, adipocytokines, and liver histology, in nondiabetic subjects with NAFLD. METHODS: A total of 215 male patients with biopsy-proven NAFLD were included. Among this group, serum levels of adiponectin, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were measured in 101 patients whose blood samples were available. RESULTS: High gamma-glutamyl transferase (GGT), high total cholesterol (TC), high triglycerides (TGs), low high-density lipoprotein cholesterol (HDL-C), and presence of metabolic syndrome were significantly associated with higher VAI, although only higher GGT and TC were independent factors on multiple linear regression analysis. On the other hand, no significant association was found between VAI and adiponectin, TNF-α, IL-6, and hsCRP levels. The multivariate analysis of variables in patients with (n=124) and without (n=91) fibrosis showed that only higher homeostasis model assessment of insulin resistance value was independently associated with liver fibrosis. CONCLUSIONS: Our findings suggest that VAI is not related to the severity of hepatic inflammation or fibrosis in nondiabetic patients with NAFLD. The lack of association between the adipocytokines and VAI also implies that the VAI may not be a significant indictor of the adipocyte functions.

Important details about the red cell distribution width.

In the recent issue of the Journal of Atherosclerosis and Thrombosis, Wang et al. assessed the relationship between the red cell distribution width (RDW) and acute myocardial infarction (AMI). However, assessing all parameters affecting the RDW, determining the optimum RDW cut-off value for predicting the prognosis of coronary artery disease (CAD), excluding metabolic comorbidities affecting the RDW values and identifying the specific range for the WBC count within the exclusion criteria would provide more reliable results and improve the credibility of the entire article in this study population.