Effects of Perioperative Glycemic Management Protocol on Glycemic Outcomes of Type 2 Diabetic Patients Undergoing Major Abdominal Surgery: A Prospective Cohort Study.

PURPOSE: This study aimed to reveal the effects of a glycemic control protocol directed by nurses during the perioperative period on glycemic outcomes in diabetic patients undergoing major abdominal surgery. DESIGN: This was a prospective cohort study METHODS: The study was conducted at the Department of General Surgery of a research and training hospital in Turkey. The study included 47 patients with type 2 diabetes mellitus who underwent elective major abdominal surgery between September 2017 and December 2018. The number of patients in the intervention and the control groups was 22 and 25, respectively. Routine clinical glycemic control was implemented in the control group, whereas a glycemic management protocol developed by a multidisciplinary team was implemented in the intervention group. We collected data on the control group first, followed by the introduction of the glycemic management protocol to clinical staff and glycemia data collection using the new protocol. Blood glucose (BG) levels in patients and the factors that may affect BG were measured in the preoperative, intraoperative, and postoperative periods. Data on glycemic control was also collected. Furthermore, we measured the satisfaction of the nurses implementing the glycemic management protocol. FINDINGS: The rate of hyperglycemia in intensive care unit was 21% in the intervention group and 59% in the control group (P < .05). Time spent in the target BG range during insulin infusion was 76% in the intervention group and 35% in the control group (P < .05). The time required to achieve target BG range during insulin infusion was 6 hours for the intervention group and 15 hours for the control group, indicating that less time was required to achieve the target BG range in the intervention group (P < .05). Moreover, the insulin consumption rate in the intensive care unit was lower in the intervention group (P < .05). The satisfaction levels of the nurses that used the glycemic management protocol was 92.61 ± 7.93%. CONCLUSIONS: Results of this study showed that the implementation of a glycemic management protocol by nurses for patients undergoing major abdominal surgery decreases the rate of hyperglycemia, insulin consumption rate, and the time required to achieve the targeted BG range during the perioperative period. Therefore, it is recommended to use a glycemia management protocol to control glycemia in patients during the surgical process.

The Clinical Characteristics and Outcomes of COVID-19 Patients with Pre-Existing Thyroid Dysfunction: A Nationwide Study.

To which extent the pre-existing hypothyroidism or hyperthyroidism has an impact on coronavirus infection 2019 (COVID-19) outcomes remains unclear. The objective of this study was to evaluate COVID-19 morbidity and mortality in patients with pre-existing thyroid dysfunction. A retrospective cohort of patients with a polymerase chain reaction (PCR)-confirmed COVID-19 infection (n=14 966) from March 11 to May 30, 2020, was established using the database of the Turkish Ministry of Health. We compared the morbidity and mortality rates of COVID-19 patients with pre-existing hypothyroidism (n=8813) and hyperthyroidism (n=1822) to those patients with normal thyroid function (n=4331). Univariate and multivariate regression analyses were performed to identify the factors associated with mortality. Mortality rates were higher in patients with hyperthyroidism (7.7%) and hypothyroidism (4.4%) than those with normal thyroid function (3.4%) (p<0.001 and p=0.008, respectively). Pre-existing hyperthyroidism was significantly associated with an increased risk of mortality (OR 1.54; 95% CI, 1.02-2.33; p=0.042) along with advanced age, male gender, lymphopenia and chronic kidney disease (p<0.001 for all). Although a potential trend was noted, the association between pre-existing hypothyroidism and mortality was not significant (OR 1.36; 95% CI, 0.99-1.86; p=0.055). In conclusion, this study showed an association between pre-existing hyperthyroidism with higher COVID-19 mortality. A potential trend towards increased mortality was also observed for hypothyroidism. The risk was more pronounced in patients with hyperthyroidism.

No association of Gaucher disease with COVID-19-related outcomes: a nationwide cohort study.

BACKGROUND: It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature. AIM: To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease. METHODS: Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality. RESULTS: The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231). CONCLUSION: According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population.

Atherosclerosis Development and Progression: The Role of Atherogenic Small, Dense LDL.

Atherosclerosis is responsible for large cardiovascular mortality in many countries globally. It has been shown over the last decades that the reduction of atherosclerotic progression is a critical factor for preventing future cardiovascular events. Low-density lipoproteins (LDL) have been successfully targeted, and their reduction is one of the key preventing measures in patients with atherosclerotic disease. LDL particles are pivotal for the formation and progression of atherosclerotic plaques; yet, they are quite heterogeneous, and smaller, denser LDL species are the most atherogenic. These particles have greater arterial entry and retention, higher susceptibility to oxidation, as well as reduced affinity for the LDL receptor. Increased proportion of small, dense LDL particles is an integral part of the atherogenic lipoprotein phenotype, the most common form of dyslipidemia associated with insulin resistance. Recent data suggest that both genetic and epigenetic factors might induce expression of this specific lipid pattern. In addition, a typical finding of increased small, dense LDL particles was confirmed in different categories of patients with elevated cardiovascular risk. Small, dense LDL is an independent risk factor for cardiovascular diseases, which emphasizes the clinical importance of both the quality and the quantity of LDL. An effective management of atherosclerotic disease should take into account the presence of small, dense LDL in order to prevent cardiovascular complications.

The clinical outcomes of COVID-19 infection in patients with a history of thyroid cancer: A nationwide study.

BACKGROUND: There are scarce published data in differentiated thyroid cancer patients about new coronavirus disease 2019 (COVID-19) disease outcomes and mortality. Here, we evaluated COVID-19 infection outcomes and mortality in thyroid cancer patients with COVID-19 infection. DESIGN AND METHODS: We included a cohort of patients with thyroid cancer with PCR-confirmed COVID-19 disease from 11 March to 30 May 2020 from the Turkish Ministry of Health database in our nationwide, retrospective study. We compared the mortality and morbidity of COVID patients with or without thyroid cancer. Univariate and multivariate analyses were used to assess the independent factors for mortality, length of hospital stay and intensive care unit (ICU) admission and mechanical ventilation. We also analysed the effect of radioiodine treatment on severity and death rate of COVID-19 disease. RESULTS: We evaluated 388 COVID-19 patients with thyroid cancer [median age: 54 years, interquartile range (IQR) 18 years, males: 23%] and age and gender-matched 388 COVID-19 patients without thyroid cancer. Patients with thyroid cancer had a similar mortality ratio compared with the non-cancer group. Among patients with thyroid cancer, age, presence of diabetes mellitus, asthma/COPD, heart failure, chronic kidney disease, prior coronary artery disease, RAS blocker usage and low lymphocyte count were associated with mortality. Radioactive iodine (RAI) treatment and cumulative radioactive iodine dosage did not negatively affect the severity and mortality of COVID-19 disease in our patient group. CONCLUSIONS: Our study indicated that history of thyroid cancer did not have an increased risk of mortality or morbidity in COVID-19 disease. Besides, RAI therapy history and doses of radioactive iodine did not affect mortality or outcome.

The Evolving Role of Fetuin-A in Nonalcoholic Fatty Liver Disease: An Overview from Liver to the Heart.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated to the features of metabolic syndrome which can progress to cirrhosis, liver failure and hepatocellular carcinoma. However, the most common cause of mortality in people with NAFLD is not liver-related but stems from atherosclerotic cardiovascular disease (CVD). The prevalence of NAFLD is on the rise, mainly as a consequence of its close association with two major worldwide epidemics, obesity and type 2 diabetes (T2D). The exact pathogenesis of NAFLD and especially the mechanisms leading to disease progression and CVD have not been completely elucidated. Human fetuin-A (alpha-2-Heremans Schmid glycoprotein), a glycoprotein produced by the liver and abundantly secreted into the circulation appears to play a role in insulin resistance, metabolic syndrome and inflammation. This review discusses the links between NAFLD and CVD by specifically focusing on fetuin-A's function in the pathogenesis of NAFLD and atherosclerotic CVD.

Utilization of statins and LDL-cholesterol target attainment in Turkish patients with type 2 diabetes - a nationwide cross-sectional study (TEMD dyslipidemia study).

BACKGROUND: Attaining acceptable levels of LDL Cholesterol (LDL-C) significantly improves cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM). The LDL-C target attainment and the characteristics of patients attaining these targets were investigated in this study. Furthermore, the reasons for not choosing statins and the physicians' attitudes on the treatment of diabetic dyslipidemia were also examined. METHODS: A nationwide, cross-sectional survey was conducted in tertiary centers for diabetes management. Adult patients with T2DM, who were under follow-up for at least a year in outpatient clinics, were consecutively enrolled for the study. LDL-C goals were defined as below 70 mg/dL for patients with macrovascular complications or diabetic nephropathy, and below 100 mg/dL for other patients. Data about lipid-lowering medications were self-reported. RESULTS: A total of 4504 patients (female: 58.6%) were enrolled for the study. The mean HbA1c and diabetes duration was 7.73 ± 1.74% and 10.9 ± 7.5 years, respectively. The need for statin treatment was 94.9% (n = 4262); however, only 42.4% (n = 1807) of these patients were under treatment, and only 24.8% (n = 448) of these patients achieved LDL-C targets. The main reason for statin discontinuation was negative media coverage (87.5%), while only a minority of patients (12.5%) mentioned side effects. Physicians initiated lipid-lowering therapy in only 20.3% of patients with high LDL-C levels. It was observed that the female gender was a significant independent predictor of not attaining LDL-C goals (OR: 0.70, 95% CI: 0.59-0.83). CONCLUSIONS: Less than 50 % of patients with T2DM who need statins were under treatment, and only a quarter of them attained their LDL-C targets. There exists a significant gap between the guideline recommendations and the real-world evidence in the treatment of dyslipidemia in T2DM.

The role of plasma triglyceride/high-density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) risk is substantially increased in subjects with chronic kidney disease (CKD). The Triglycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C) ratio is an indirect measure of insulin resistance and an independent predictor of cardiovascular risk. No study to date has been performed to evaluate whether the TG/HDL-C ratio predicts CVD risk in patients with CKD. METHODS: A total of 197 patients (age 53±12 years) with CKD Stages 1 to 5, were enrolled in this longitudinal, observational, retrospective study. TG/HDL-C ratio, HOMA-IR indexes, serum asymmetric dimethyl arginine (ADMA), high sensitivity C-reactive protein (CRP), parathyroid hormone (PTH), calcium, phosphorous, estimated glomerular filtration rate (eGFR), and albumin levels were measured. Flow mediated vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasonography. RESULTS: A total of 11 cardiovascular (CV) deaths and 43 nonfatal CV events were registered in a mean follow-up period of 30 (range 9 to 35) months. Subjects with TG/HDL-C ratios above the median values (>3.29) had significantly higher plasma ADMA, PTH, and phosphorous levels (p=0.04, p=0.02, p=0.01 respectively) and lower eGFR and FMD values (p=0.03, p<0.001 respectively). The TG/HDL-C ratio was an independent determinant of FMD (ß=-0.25 p=0.02) along with TG, HDL-C, hsCRP, serum albumin, phosphate levels, systolic blood pressure, PTH, eGFR and the presence of diabetes mellitus. The TG/HDL-C ratio was also a significant independent determinant of cardiovascular outcomes [HR: 1.36 (1.11-1.67) (p=0.003)] along with plasma ADMA levels [HR: 1.31 (1.13-1.52) (p<0.001)] and a history of diabetes mellitus [HR: 4.82 (2.80-8.37) (p<0.001)]. CONCLUSION: This study demonstrates that the elevated TG/HDL-C ratio predicts poor CVD outcome in subjects with CKD. Being a simple, inexpensive, and reproducible marker of CVD risk, the TG/HDL-C ratio may emerge as a novel and reliable indicator among the many well-established markers of CVD risk in CKD. SYSTEMATIC REVIEW REGISTRATION: Clinical trial registration number and date: NCT02113462 / 10-04-2014.

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.

Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events.

OBJECTIVES: Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. METHODS: We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. RESULTS: Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis. CONCLUSION: Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients.

Ramipril lowers plasma FGF-23 in patients with diabetic nephropathy.

BACKGROUND/AIMS: Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition. METHODS: In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32). RESULTS: Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage. CONCLUSION: Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)).

Expert Opinion on the Utility of Telemedicine in Obesity Care: Recommendations on a Hybrid Multidisciplinary Integrated Care Follow-Up Algorithm.

PURPOSE OF REVIEW: The proposed expert opinion was prepared by a panel of obesity and law specialists from Turkey to review the utility of telemedicine in obesity care and to provide a guidance document with recommendations on a hybrid multidisciplinary integrated care follow-up algorithm and the legislation governing telemedicine practice to assist obesity specialists in practicing the telemedicine. RECENT FINDINGS: The efficacy and feasibility of telemedicine interventions in supporting obesity management programs even during pandemics confirm that obesity is a particularly well-suited field for telemedicine, emphasizing the strong likelihood of continued utilization of telemedicine in obesity management, beyond the pandemic period. Telemedicine has great potential to address several barriers to ongoing weight-management care, such as challenges of access to specialized care, cost, and time limitations as well as patient adherence to treatment. However, telemedicine practice should complement rather than replace the in-person visits which are unique in building rapport and offering social support. Accordingly, the participating experts recommend the use of a hybrid integrated care model in the management of obesity, with the use of telemedicine, as an adjunct to in-person visits, to enable the provision of suggested intensive obesity management via frequent visits by a multidisciplinary team of obesity specialists. Further research addressing the utility of telemedicine in terms of optimal modality and duration for successful long-term obesity management outcomes is necessary to develop specific guidelines on telemedicine practice. In addition, the legislation governing the norms and protocols on confidentiality, privacy, access, and liability needs to be improved.

Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3-year experience.

INTRODUCTION: The aim of this study was to demonstrate the influences of three different treatment strategies on biochemical parameters and testicular volume (TV) in patients with idiopathic hypogonadotropic hypogonadism (IHH). SUBJECTS DESIGN AND METHODS: Seventy-seven never-treated patients with IHH and age and body mass index (BMI)-matched 42 healthy controls were analysed in a retrospective design. Twenty-eight patients were treated with testosterone esters (TE), 25 patients were treated with human chorionic gonadotropin (hCG) and 24 patients were treated with testosterone gel (TG). Biochemical parameters, tanner stages (TS) and TV were evaluated before and after 6 months of treatment. RESULTS: Pretreatment TV, TS and biochemical test results were similar among the three treatment subgroup. In the TE-treated group, BMI, haemoglobin, haematocrit, creatinine, triglyceride, total testosterone (TT), TS and TV increased, but HDL-cholesterol (C) and urea level decreased significantly. In the hCG-treated group, triglyceride level decreased, and luteinizing hormone level, TS and TV increased significantly. BMI, TT, TS and TV increased, and leucocyte count, total-C, HDL-C levels decreased significantly in the TG-treated patients. No treatment type resulted in any changes in insulin resistance markers. CONCLUSION: hCG treatment resulted in favourable effects particularly on TV and lipid parameters. When TV improvement is considered less important, TG treatment may be a better option for older patients with IHH because of its easy use, neutral effects on triglyceride, haemoglobin and haematocrit, and its beneficial effects on total cholesterol level.

Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin-A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin-A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD. METHODS: The consecutive 115 patients with NAFLD and age-matched 74 healthy subjects were enrolled. Plasma levels of fetuin-A and markers of endothelial dysfunction [asymmetric dimethyl arginine (ADMA) and adiponectin] were measured by ELISA method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Carotid artery intima-media thickness (cIMT) was assessed by high-resolution ultrasonography. RESULTS: Fetuin-A and ADMA were higher and, adiponectin was lower in NAFLD group than the control group (P = 0·004, P < 0·001 and P < 0·001, respectively). In addition, NAFLD group had greater cIMT measurements than the controls (P < 0·001). However, no difference was found for fetuin-A, ADMA, adiponectin and cIMT between two groups when the findings were adjusted according to the glucose, lipids and HOMA-IR index. In correlation analysis, fetuin-A was found to be positively correlated with triglyceride (r = 0·23, P = 0·001), HOMA-IR (r = 0·29, P < 0·001), ADMA (r = 0·24, P = 0·001), cIMT (r = 0·3, P = 0·003) and, negatively correlated with HDL-C (r = -0·17, P = 0·02) and adiponectin (r = -0·19, P = 0·01) levels. Multiple linear regression analysis showed that fetuin-A was independently associated with ADMA and cIMT levels. CONCLUSION: This study demonstrated for the first time that circulating fetuin-A in NAFLD is independently associated with endothelial dysfunction and subclinical atherosclerosis.

Soluble TWEAK plasma levels increase after renal transplantation and associate with the improvement of endothelial function.

BACKGROUND: Soluble TWEAK (sTWEAK) and asymmetric dimethyl arginine (ADMA) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). We tested the hypothesis that the improvement in endothelial function observed after renal transplantation is directly linked to the normalization of both sTWEAK and ADMA. MATERIALS AND METHODS: One hundred and seventy-five kidney transplant recipients (71% men; 31·6 ± 9·4 years) were studied immediately before and on the 180th day post-transplantation. At each visit, blood samples were taken to assess circulating levels of sTWEAK and ADMA. Brachial artery endothelium-dependent vasodilatation (FMD) assessments were also performed. RESULTS: Renal transplantation was followed by an improvement in FMD. This improvement was paralleled by an increase in sTWEAK and a reduction in ADMA after transplantation (P < 0·001 for all). Cross-sectionally, both molecules associated with FMD before as well as after transplantation (P < 0·001 for all). Longitudinally, the changes observed in sTWEAK (ß = 0·26, P < 0·001) and ADMA (ß = -0·44, P < 0·001) levels were independently associated with the improvement of FMD (r(2)  = 0·30). CONCLUSIONS: Renal transplantation is followed by an improvement of FMD that is independently associated with the normalization of both sTWEAK and ADMA concentrations. We identify two surrogate biomarkers of endothelial function with potential as therapeutic targets.

Longitudinal analysis of vascular function and biomarkers of metabolic bone disorders before and after renal transplantation.

BACKGROUND/AIMS: The role of chronic kidney disease-mineral bone disorder (CKD-MBD) reversibility in the amelioration of vascular function and in the reduction of the risk for cardiovascular events after renal transplantation is still unknown. METHODS: We investigated the longitudinal relationship between the main biomarkers of CKD-MBD and the evolution of vascular function [flow-mediated dilatation (FMD)] after transplantation in a series of 161 patients with kidney failure maintained on chronic dialysis (5D-CKD). RESULTS: Before transplantation, FMD in patients was markedly lower (-40%, p < 0.001) than in well-matched healthy subjects and increased by 27% after transplantation (p = 0.001). Fibroblast growth factor 23 (FGF23), 25-hydroxy-vitamin D (25OHVD) and serum phosphate (p < 0.01) were independently associated with simultaneous changes in FMD. Changes in classical risk factors and in risk factors related to CKD like the glomerular filtration rate, serum albumin, C-reactive protein and insulin resistance failed to independently explain the variability in FMD changes after transplantation. CONCLUSION: Endothelium-dependent vasodilatation improves after kidney transplantation, which is parallel to the dramatic fall in FGF23, the reduction in serum phosphorus and the increase in 25OHVD levels. If these associations are causal, a part of decline in cardiovascular risk after transplantation is related to partial resolution of CKD-MBD.

Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease.

BACKGROUND: Increased inflammation is common in patients with chronic kidney disease (CKD) and is associated with increased adverse cardiovascular events (CVE). Neutrophil-to-lymphocyte ratio (NLR) was used to predict survival in patients with acute coronary syndrome. We aimed to evaluate predictive ability of NLR in CKD patients. METHODS: 225 subjects with stage 3-5 CKD were followed for a mean of 39 months. Fatal and nonfatal CVE were recorded during this period. NLR at baseline was determined from complete blood count differential. Endothelial dysfunction (flow-mediated dilation, FMD), hsCRP and insulin resistance were determined. We investigated if NLR could predict development of fatal and nonfatal CVE. We also looked at how NLR and its individual components change across CKD stages and whether NLR is related to CRP, insulin resistance and endothelial dysfunction. RESULTS: There were 70, 74 and 81 patients in groups of CKD stage-3, stage-4 and stage-5, respectively. Median NLR was 2.81. NLR showed a significant increase from stage 3 to stage 5. NLR was inversely associated with FMD independent of hsCRP. 14 fatal and 52 nonfatal CVE occurred during follow-up period. NLR could predict composite CVE independent of insulin resistance and hsCRP. Increased NLR over 2.81 was related to a significantly decreased survival time (log-rank Chi-square = 14.833, P < 0.0001). A cutoff value for NLR ≥3.76 could predict development of composite CVE with 80.3 % sensitivity and 91.8 % specificity. CONCLUSIONS: NLR is independently related to endothelial dysfunction and could predict composite cardiovascular endpoints independent of traditional confounding factors in patients with moderate to severe CKD.

Increase in subcutaneous adipose tissue and fat free mass in women with polycystic ovary syndrome is related to impaired insulin sensitivity.

OBJECTIVES: The present study was performed to search whether subcutaneous and whole body adipose tissue increase and they relate to measures of insulin sensitivity in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: 52 women with PCOS and 53 healthy controls, all with similar age and body mass index participated in the study. A skinfold caliper device was used to measure biceps, triceps, subscapular and suprailiac skinfold thickness (SFT). Mid-upper arm circumference (MUAC) was measured using a tape measure. Body fat distributions were determined by bioelectrical impedance analysis. Insulin resistance score was computed with the HOMA formula. Plasma adiponectin was measured by EIA. RESULTS: SFT in all defined areas, MUAC, total body and trunk fat free mass, and HOMA score were higher in women with PCOS compared with healthy women, while adiponectin level was significantly lower. SFT values correlated positively with HOMA score, and negatively with blood adiponectin level. Regression analysis indicated, SFT in triceps and supscapular areas, trunk fat mass, trunk fat ratio, fat free mass and trunk fat free mass values as the most powerful predictors of HOMA score. CONCLUSIONS: The present study showed that SFT in different body regions and fat-free tissue mass are increased in women with PCOS, with a significant relation to impaired insulin sensitivity.

Triglyceride-glucose index levels in patients with Klinefelter syndrome and its relationship with endothelial dysfunction and insulin resistance: a cross-sectional observational study.

Objective: This study aimed to investigate the triglyceride-glucose (TyG) index, which is a simple surrogate marker of insulin resistance that is associated with various cardiometabolic diseases, in patients with Klinefelter syndrome (KS). Subjects and methods: A total of 30 patients with KS (mean age: 21.53 ± 1.66 years) and 32 healthy controls (mean age: 22.07 ± 1.01 years) were included in the study. The clinical and laboratory parameters, TyG index, asymmetric dimethylarginine (ADMA) level, homeostatic model assessment of insulin resistance (HOMA-IR) score, and high-sensitivity C-reactive protein level were measured in patients with KS and healthy subjects. Results: Patients with KS had higher HOMA-IR score (p = 0.043), ADMA levels (p < 0.001), and TyG index (p = 0.031) and lower high-density lipoprotein cholesterol levels (p < 0.001) than healthy subjects. TyG index was positively correlated with plasma ADMA (r = 0.48, p < 0.001) and HOMA-IR (r = 0.36, p = 0.011). Multivariate analyses showed that total testosterone level (ß = -0.44, p = 0.001) and TyG index (ß = 0.29, p = 0.045) were independent determinants of plasma ADMA levels. Conclusion: Patients with KS had higher TyG indices than healthy subjects. Moreover, TyG index was independently associated with endothelial dysfunction in patients. TyG index may be a practical and useful measure to show the increased endothelial dysfunction in patients with KS.