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Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HR Q4vsQ1 = 0.95, 95% CI: 0.73-1.23; P trend = .97; and HR per doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73–1.23; Ptrend =.97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84–1.19; P =.98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73–1.23; Ptrend =.97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84–1.19; P =.98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

BackgroundSepsis mortality has remained unchanged for greater than a decade, and early recognition continues to be the most important factor in mortality outcome. Plasma resistin concentration is increased in sepsis, but its mechanism and clinical relevance is unclear. As one function, resistin interacts with toll-like receptor 4 in competition with lipopolysaccharide, a main component of the gram-negative bacterial cell wall. It is not known if the type of infection leading to sepsis influences resistin production. The objective of this study was to investigate whether 1) early plasma resistin concentration can predict mortality, 2) elevated plasma resistin concentration is associated with clinical disease severity scores, such as SOFA, mSOFA and APACHE II, and 3) plasma resistin concentrations differ between gram negative versus other etiologies of sepsis.MethodsThis was an exploratory study in the framework of a prospective observational design. Peripheral venous blood samples were obtained from subjects admitted to the intensive care unit at clinical recognition of sepsis (0 hour) and at 6 and 24 hours. Vasopressor utilization was not a requirement for inclusion. Plasma was analyzed for resistin concentration by ELISA. Cytokine concentrations including IL-6, IL-8, and IL-10 were determined by cytokine bead array. Cytokine data were evaluated against publicly available sepsis RNA expression datasets to compare protein versus RNA expression levels in predicting clinical disease state. Clinical data were collected from electronic health records for clinical severity index calculations and context for interpretation of resistin and cytokine concentrations. Subjects were followed up to 60 days, or until death, whichever came first. Statistical analysis was completed with R package and SPSS software.ResultsResistin levels were elevated in subjects admitted to the intensive care unit with sepsis. Four-hundred subjects were screened with 45 subjects included in the fina

AimsResistin is a circulating inflammatory biomarker that is associated with cardiovascular disease. We investigated the associations of resistin and incident heart failure (HF) and its subtypes, as well as specific measures of subclinical HF (myocardial fibrosis and relevant biomarkers).MethodsWe analysed data from 1968 participants in the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels at clinic visits from 2002 to 2005. Participants were subsequently followed for a median of 10.5 years for HF events. The associations between resistin levels and incident HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF) were examined using multivariable Cox proportional hazards models. Linear regression models assessed the associations between resistin levels and myocardial fibrosis from cardiac magnetic resonance imaging, as well as hs-cTnT and NT-proBNP.ResultsThe mean age of the cohort was 64.7 years, and 50.0% were female. Seventy-four participants (4%) developed incident HF during follow-up. In a Cox proportional hazards model adjusted for age, gender, education level, race/ethnicity, and traditional risk factors, higher resistin levels were significantly associated with incident HF (HR 1.44, CI 1.18-1.75, P = 0.001) and HFrEF (HR 1.47, CI 1.07-2.02, P = 0.016), but not with HFpEF (HR 1.25, CI 0.89-1.75, P = 0.195). Resistin levels showed no significant associations with myocardial fibrosis, NT-proBNP, or hs-cTnT levels.ConclusionsIn a multi-ethnic cohort free of cardiovascular disease at baseline, elevated resistin levels were associated with incident HF, more prominently with incident HFrEF than HFpEF, but not with subclinical myocardial fibrosis or biomarkers of HF.

BackgroundSepsis mortality has remained unchanged for greater than a decade, and early recognition continues to be the most important factor in mortality outcome. Plasma resistin concentration is increased in sepsis, but its mechanism and clinical relevance is unclear. As one function, resistin interacts with toll-like receptor 4 in competition with lipopolysaccharide, a main component of the gram-negative bacterial cell wall. It is not known if the type of infection leading to sepsis influences resistin production. The objective of this study was to investigate whether 1) early plasma resistin concentration can predict mortality, 2) elevated plasma resistin concentration is associated with clinical disease severity scores, such as SOFA, mSOFA and APACHE II, and 3) plasma resistin concentrations differ between gram negative versus other etiologies of sepsis.MethodsThis was an exploratory study in the framework of a prospective observational design. Peripheral venous blood samples were obtained from subjects admitted to the intensive care unit at clinical recognition of sepsis (0 hour) and at 6 and 24 hours. Vasopressor utilization was not a requirement for inclusion. Plasma was analyzed for resistin concentration by ELISA. Cytokine concentrations including IL-6, IL-8, and IL-10 were determined by cytokine bead array. Cytokine data were evaluated against publicly available sepsis RNA expression datasets to compare protein versus RNA expression levels in predicting clinical disease state. Clinical data were collected from electronic health records for clinical severity index calculations and context for interpretation of resistin and cytokine concentrations. Subjects were followed up to 60 days, or until death, whichever came first. Statistical analysis was completed with R package and SPSS software.ResultsResistin levels were elevated in subjects admitted to the intensive care unit with sepsis. Four-hundred subjects were screened with 45 subjects included in the fina

AimsResistin is a circulating inflammatory biomarker that is associated with cardiovascular disease. We investigated the associations of resistin and incident heart failure (HF) and its subtypes, as well as specific measures of subclinical HF (myocardial fibrosis and relevant biomarkers).MethodsWe analysed data from 1968 participants in the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels at clinic visits from 2002 to 2005. Participants were subsequently followed for a median of 10.5 years for HF events. The associations between resistin levels and incident HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF) were examined using multivariable Cox proportional hazards models. Linear regression models assessed the associations between resistin levels and myocardial fibrosis from cardiac magnetic resonance imaging, as well as hs-cTnT and NT-proBNP.ResultsThe mean age of the cohort was 64.7 years, and 50.0% were female. Seventy-four participants (4%) developed incident HF during follow-up. In a Cox proportional hazards model adjusted for age, gender, education level, race/ethnicity, and traditional risk factors, higher resistin levels were significantly associated with incident HF (HR 1.44, CI 1.18-1.75, P = 0.001) and HFrEF (HR 1.47, CI 1.07-2.02, P = 0.016), but not with HFpEF (HR 1.25, CI 0.89-1.75, P = 0.195). Resistin levels showed no significant associations with myocardial fibrosis, NT-proBNP, or hs-cTnT levels.ConclusionsIn a multi-ethnic cohort free of cardiovascular disease at baseline, elevated resistin levels were associated with incident HF, more prominently with incident HFrEF than HFpEF, but not with subclinical myocardial fibrosis or biomarkers of HF.

Background: Multiparity is a risk factor for cardiovascular disease (CVD). However, the mechanisms of this relationship are unknown. Adipokines may predispose multiparous women to certain cardiometabolic complications that can increase their risk of future CVD. Materials and Methods: We studied 973 female participants of the Multi-Ethnic Study of Atherosclerosis free of CVD, who had complete data on parity and adipokines measured at Examination 2 or 3 (randomly assigned). Parity was categorized as nulliparity, 1-2, 3-4, and ≥5 live births. Multivariable linear regression was used to evaluate the association of parity with leptin, resistin, and adiponectin levels. Results: The women had mean age of 65 ± 9 years. After adjustment for age, race/ethnicity, study site, education, menopause status, smoking, physical activity, use of hormone therapy, and waist circumference, a history of grand multiparity (≥5 live births) was associated with 11% higher resistin levels (95% confidence interval [CI] 0-23) and 3-4 live births was associated with 23% higher leptin levels (95% CI 7-42), compared with nulliparity. After adjustment for computed tomography-measured visceral fat, the association of 3-4 live births with leptin remained significant. There were no significant associations of parity with adipokines after further adjustment for additional CVD risk factors. Multigravidity (but not parity) was inversely associated with adiponectin levels. Conclusions: In a multiethnic cohort of women, greater parity was associated with resistin and leptin; however, this association was attenuated after accounting for CVD risk factors. Dysregulation of adipokines could contribute to the excess CVD risk associated with multiparity. Further studies are needed to determine whether adipokines independently mediate the relationship between multiparity and CVD. Clinical trials registration: The MESA cohort is registered at NCT00005487.

Aim: Hypertension, obesity, insulin resistance and lipid levels are risk factors for cardiovascular disease. The association of cardiovascular risk with C-reactive protein and homocysteine has been debated for decades. Resistin and microalbuminuria are presumed to be associated with diabetes mellitus, insulin resistance and cardiovascular disease. The objective of our study was to investigate the relationship of microalbuminuria with antropometric and metabolic parameters, C-reactive protein, homocyteine and resistin in non-diabetic hypertensive females. Methods: We conducted a randomized study including 37 female non-diabetic hypertensives without microalbuminuria and 47 female non-diabetic hypertensive patients with microalbuminuria. We made comparisons of anthropometric and metabolic parameters, C-reactive protein, homocysteine, insulin resistance index and resistin between the groups. Results: C-reactive protein, homocysteine, resistin, insulin levels and homeostasis model assessment of insulin resistance were higher in hypertensives with microalbuminuria than in hypertensives without microalbuminuria (all p0.05). Conclusion: We found that microalbuminuria may have an influence on C-reactive protein, homocysteine and resistin levels in non-diabetic hypertensives. We also think that insulin and insulin resistance may also be related with microalbuminuria in nondiabetic hypertensive female patients.

Aim: Hypertension, obesity, insulin resistance and lipid levels are risk factors for cardiovascular disease. The association of cardiovascular risk with C-reactive protein and homocysteine has been debated for decades. Resistin and microalbuminuria are presumed to be associated with diabetes mellitus, insulin resistance and cardiovascular disease. The objective of our study was to investigate the relationship of microalbuminuria with antropometric and metabolic parameters, C-reactive protein, homocyteine and resistin in non-diabetic hypertensive females. Methods: We conducted a randomized study including 37 female non-diabetic hypertensives without microalbuminuria and 47 female non-diabetic hypertensive patients with microalbuminuria. We made comparisons of anthropometric and metabolic parameters, C-reactive protein, homocysteine, insulin resistance index and resistin between the groups. Results: C-reactive protein, homocysteine, resistin, insulin levels and homeostasis model assessment of insulin resistance were higher in hypertensives with microalbuminuria than in hypertensives without microalbuminuria (all p0.05). Conclusion: We found that microalbuminuria may have an influence on C-reactive protein, homocysteine and resistin levels in non-diabetic hypertensives. We also think that insulin and insulin resistance may also be related with microalbuminuria in nondiabetic hypertensive female patients.

Producción Científica, Background:The single nucleotide polymorphism (SNP) (rs10401670) of theRETNgene has been associated with metabolic disorder in obese subjects andhas scarcely been evaluated after dietary interventions. The present studyaimed to analyse the effects of thers10401670 RETNgene polymorphismon metabolic changes secondary to weight loss and secondary to a high‐fathypocaloric diet with a Mediterranean dietary pattern.Methods:A Caucasian population comprising 284 obese patients withoutdiabetes mellitus was analysed. Before and after 3 months of a high‐fathypocaloric diet with a Mediterranean pattern, an anthropometric evaluation,an assessment of nutritional intake and a biochemical analysis were per-formed. A statistical analysis was conducted for the combinedCTandTTas agroup and for wild‐typeCCas a second group.Results:Decreases in weight, body mass index (BMI), fat mass, systolic bloodpressure and waist circumference were similar in both genotypes groups. InTallele carriers, insulin, homeostatic model assessment for insulin resistance(HOMA‐IR), triglycerides and C‐reactive protein levels were decreased.The decrease in these parameters was statistically significant for triglycerides(−22.3 ± 9.3 mg dl–1:p= 0.03), C‐reactive protein (−2.8 ± 0.5 mg dl–1:p= 0.03), insulin (−7.4 ± 2.9 mUI L–1:p= 0.03) and HOMA‐IR (−2.4 ± 1.0:p= 0.02). Leptin levels were decreased in both genotypes groups after thehypocaloric diet, as well as the anthropometric parameters BMI, weight, waistcircumference and fat mass. Resistin and adiponectin levels remained un-changed in both groups.Conclusions:In the present study, we have detected a significant associationbetween theTallele of this SNP and a better response of insulin resistance,triglycerides and C‐reactive protein compared to nonTallele carriers afterweight loss with a high‐fat hypocaloric diet and a Mediterranean diet.

Background/Purpose: Metabolic syndrome (MetS) is a chronic pro-inflammatory and pro-thrombotic state associated with increased atherosclerosis, cardiovascular events and type 2 diabetes. It is diagnosed in the presence of at least 3 of 5 metabolic risk factors (obesity, hypertension, hypertriglyceridemia, low high-density lipoproteins (HDL) and insulin resistance [1]). The pathophysiology of MetS remains incompletely understood, but may share mechanisms with inflammatory states such as SLE. Visceral adiposity is known as a source of pro-inflammatory cytokines by adipocytes, the so-called adipokines. The contribution of glucocorticoids to the development of MetS in SLE is not clear, even though their use is associated with cardiovascular comorbidities [2]. We aim to characterize the prevalence and associations of MetS, including serum levels of adipokines, in a multi-ethnic cohort of patients with SLE. Method(s): Using a standardised protocol, baseline demographics, per visit disease activity (SLEDAI2K) and treatment data, and annual recording of organ damage accrual (SLICC damage index (SDI)) were prospectively captured on SLE patients from a single tertiary centre. The presence of MetS,defined using the updated joint consensus criteria [1], was assessed retrospectively at the last recorded visit. Serum levels of adipokines (resistin, lipocalin-2, TNF, MCP-1) and insulin were measured by Quantibody. Result(s): 116 patients (median (IQR) age at enrolment 39.5 (31.4-51.1) years, median disease duration 6.1 (1.4-12) years) were followed for a median of 6.7 (4.1-8.1) years. 80% of patients were exposed to glucocorticoids (median time-adjusted mean dose 3.7 (0.5-7.0) mg/day and 50% accrued organ damage during follow-up. The prevalence of MetS in this cohort was 29%. The prevalence of the components of MetS included: hypertension (59%), low-HDL (51%), hypertriglyceridemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with base

Background/Purpose: Metabolic syndrome (MetS) is a chronic pro-inflammatory and pro-thrombotic state associated with increased atherosclerosis, cardiovascular events and type 2 diabetes. It is diagnosed in the presence of at least 3 of 5 metabolic risk factors (obesity, hypertension, hypertriglyceridemia, low high-density lipoproteins (HDL) and insulin resistance [1]). The pathophysiology of MetS remains incompletely understood, but may share mechanisms with inflammatory states such as SLE. Visceral adiposity is known as a source of pro-inflammatory cytokines by adipocytes, the so-called adipokines. The contribution of glucocorticoids to the development of MetS in SLE is not clear, even though their use is associated with cardiovascular comorbidities [2]. We aim to characterize the prevalence and associations of MetS, including serum levels of adipokines, in a multi-ethnic cohort of patients with SLE. Method(s): Using a standardised protocol, baseline demographics, per visit disease activity (SLEDAI2K) and treatment data, and annual recording of organ damage accrual (SLICC damage index (SDI)) were prospectively captured on SLE patients from a single tertiary centre. The presence of MetS,defined using the updated joint consensus criteria [1], was assessed retrospectively at the last recorded visit. Serum levels of adipokines (resistin, lipocalin-2, TNF, MCP-1) and insulin were measured by Quantibody. Result(s): 116 patients (median (IQR) age at enrolment 39.5 (31.4-51.1) years, median disease duration 6.1 (1.4-12) years) were followed for a median of 6.7 (4.1-8.1) years. 80% of patients were exposed to glucocorticoids (median time-adjusted mean dose 3.7 (0.5-7.0) mg/day and 50% accrued organ damage during follow-up. The prevalence of MetS in this cohort was 29%. The prevalence of the components of MetS included: hypertension (59%), low-HDL (51%), hypertriglyceridemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with base

Producción Científica, Background:The single nucleotide polymorphism (SNP) (rs10401670) of theRETNgene has been associated with metabolic disorder in obese subjects andhas scarcely been evaluated after dietary interventions. The present studyaimed to analyse the effects of thers10401670 RETNgene polymorphismon metabolic changes secondary to weight loss and secondary to a high‐fathypocaloric diet with a Mediterranean dietary pattern.Methods:A Caucasian population comprising 284 obese patients withoutdiabetes mellitus was analysed. Before and after 3 months of a high‐fathypocaloric diet with a Mediterranean pattern, an anthropometric evaluation,an assessment of nutritional intake and a biochemical analysis were per-formed. A statistical analysis was conducted for the combinedCTandTTas agroup and for wild‐typeCCas a second group.Results:Decreases in weight, body mass index (BMI), fat mass, systolic bloodpressure and waist circumference were similar in both genotypes groups. InTallele carriers, insulin, homeostatic model assessment for insulin resistance(HOMA‐IR), triglycerides and C‐reactive protein levels were decreased.The decrease in these parameters was statistically significant for triglycerides(−22.3 ± 9.3 mg dl–1:p= 0.03), C‐reactive protein (−2.8 ± 0.5 mg dl–1:p= 0.03), insulin (−7.4 ± 2.9 mUI L–1:p= 0.03) and HOMA‐IR (−2.4 ± 1.0:p= 0.02). Leptin levels were decreased in both genotypes groups after thehypocaloric diet, as well as the anthropometric parameters BMI, weight, waistcircumference and fat mass. Resistin and adiponectin levels remained un-changed in both groups.Conclusions:In the present study, we have detected a significant associationbetween theTallele of this SNP and a better response of insulin resistance,triglycerides and C‐reactive protein compared to nonTallele carriers afterweight loss with a high‐fat hypocaloric diet and a Mediterranean diet.

Producción Científica, Background:The single nucleotide polymorphism (SNP) (rs10401670) of theRETNgene has been associated with metabolic disorder in obese subjects andhas scarcely been evaluated after dietary interventions. The present studyaimed to analyse the effects of thers10401670 RETNgene polymorphismon metabolic changes secondary to weight loss and secondary to a high‐fathypocaloric diet with a Mediterranean dietary pattern.Methods:A Caucasian population comprising 284 obese patients withoutdiabetes mellitus was analysed. Before and after 3 months of a high‐fathypocaloric diet with a Mediterranean pattern, an anthropometric evaluation,an assessment of nutritional intake and a biochemical analysis were per-formed. A statistical analysis was conducted for the combinedCTandTTas agroup and for wild‐typeCCas a second group.Results:Decreases in weight, body mass index (BMI), fat mass, systolic bloodpressure and waist circumference were similar in both genotypes groups. InTallele carriers, insulin, homeostatic model assessment for insulin resistance(HOMA‐IR), triglycerides and C‐reactive protein levels were decreased.The decrease in these parameters was statistically significant for triglycerides(−22.3 ± 9.3 mg dl–1:p= 0.03), C‐reactive protein (−2.8 ± 0.5 mg dl–1:p= 0.03), insulin (−7.4 ± 2.9 mUI L–1:p= 0.03) and HOMA‐IR (−2.4 ± 1.0:p= 0.02). Leptin levels were decreased in both genotypes groups after thehypocaloric diet, as well as the anthropometric parameters BMI, weight, waistcircumference and fat mass. Resistin and adiponectin levels remained un-changed in both groups.Conclusions:In the present study, we have detected a significant associationbetween theTallele of this SNP and a better response of insulin resistance,triglycerides and C‐reactive protein compared to nonTallele carriers afterweight loss with a high‐fat hypocaloric diet and a Mediterranean diet.

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross‐sectional study, we aimed to investigate the potential mediating role of T‐EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA‐IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower‐weight subgroups. Linear regression analysis revealed that an elevated HOMA‐IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist‐to‐hip ratio on HOMA‐IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Producción Científica, Background:The single nucleotide polymorphism (SNP) (rs10401670) of theRETNgene has been associated with metabolic disorder in obese subjects andhas scarcely been evaluated after dietary interventions. The present studyaimed to analyse the effects of thers10401670 RETNgene polymorphismon metabolic changes secondary to weight loss and secondary to a high‐fathypocaloric diet with a Mediterranean dietary pattern.Methods:A Caucasian population comprising 284 obese patients withoutdiabetes mellitus was analysed. Before and after 3 months of a high‐fathypocaloric diet with a Mediterranean pattern, an anthropometric evaluation,an assessment of nutritional intake and a biochemical analysis were per-formed. A statistical analysis was conducted for the combinedCTandTTas agroup and for wild‐typeCCas a second group.Results:Decreases in weight, body mass index (BMI), fat mass, systolic bloodpressure and waist circumference were similar in both genotypes groups. InTallele carriers, insulin, homeostatic model assessment for insulin resistance(HOMA‐IR), triglycerides and C‐reactive protein levels were decreased.The decrease in these parameters was statistically significant for triglycerides(−22.3 ± 9.3 mg dl–1:p= 0.03), C‐reactive protein (−2.8 ± 0.5 mg dl–1:p= 0.03), insulin (−7.4 ± 2.9 mUI L–1:p= 0.03) and HOMA‐IR (−2.4 ± 1.0:p= 0.02). Leptin levels were decreased in both genotypes groups after thehypocaloric diet, as well as the anthropometric parameters BMI, weight, waistcircumference and fat mass. Resistin and adiponectin levels remained un-changed in both groups.Conclusions:In the present study, we have detected a significant associationbetween theTallele of this SNP and a better response of insulin resistance,triglycerides and C‐reactive protein compared to nonTallele carriers afterweight loss with a high‐fat hypocaloric diet and a Mediterranean diet.

Cardiovascular (CV) diseases are the number one cause of mortality worldwide, causing nearly 19 million deaths in 2019. Estimating the individual CV risk is essential for targeting the preventative interventions more effectively. Currently, international guidelines recommend using standardized risk calculators for estimating the patient’s future risk of a CV event. In “borderline” risk individuals, these guidelines further recommend using additional clinical tests, such as coronary artery calcium score, for refining the risk estimation and guiding the clinical treatment decisions. Relatively little is known about much simpler and safer clinical tests in CV risk assessment. The aim of the current study was to explore whether plasma resistin concentration, carotid or femoral bruits, or ultrasonographically assessed carotid intima-media thickness (IMT) and abdominal aorta plaques could provide additional prognostic information beyond traditional CV risk factors in individual risk assessment. The study population consisted of middle-aged and elderly Finnish subjects participating in the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) project. Our results show that increasing plasma resistin concentration is associated with significantly increased risk of all-cause mortality in elderly Finnish participants. Similarly, our results show that an audible bruit from either carotid or femoral arteries is a strong predictor of fatal CV events in a middle-aged population. Ultrasonographically assessed carotid IMT is a controversial surrogate marker of subclinical atherosclerosis, and our results indicate that it does not predict CV events after adjusting for other CV risk factors. On the other hand, our results show that ultrasonographically measured abdominal aorta plaque length is a strong predictor of future CV events and provides prognostic information in addition to traditional CV risk factors during a follow-up period of over 20 years. In conclusion, this, Tiivistelmä Sydän- ja verisuonisairaudet (SV) ovat maailman yleisin kuolleisuuden syy aiheuttaen lähes 19 miljoonaa kuolemaa vuonna 2019. Yksilöllinen SV-sairauksien riskinarvio on ensiarvoisen tärkeää ennaltaehkäisevien toimenpiteiden tehokkaassa kohdentamisessa. Kansainväliset suositukset suosittelevat riskilaskureiden käyttöä potilaan tulevan SV-tapahtuman riskinarviossa. Samat suositukset kehottavat käyttämään tarkentavia kliinisiä tutkimuksia, kuten sepelvaltimoiden kalsifikaatioiden pisteytystä, riskinarvion ja kliinisten hoitopäätösten tukena yksilöillä, joiden SV-tapahtuman riski on ”rajaviivalla”. Verrattain vähän tiedetään paljon yksinkertaisemmista kliinisistä testeistä SV-tapahtumien riskinarviossa. Tämän tutkimuksen tarkoitus oli selvittää tuovatko plasman resistiinipitoisuus, kaula- tai reisivaltimosta kuullut suhinat tai ultraäänellä määritetty kaulavaltimon intima-media paksuus (IMT) ja vatsa-aortan plakkien pituus prognostista informaatiota tavanomaisten SV-sairauksien riskitekijöiden lisäksi yksilöllisessä riskinarviossa. Tutkimuksen aineisto koostuu keski-ikäisistä ja iäkkäistä suomalaisista, jotka osallistuivat Oulu Project Elucidating Risk of Atherosclerosis (OPERA) -projektiin. Tuloksemme osoittavat, että kohonnut plasman resistiinipitoisuus on yhteydessä merkittävästi kohonneeseen kuolleisuuteen iäkkäillä henkilöillä. Vastaavasti tuloksemme osoittavat, että joko kaula- tai reisivaltimosta auskultoiden kuultu suhina on voimakas fataalien SV-tapahtumien ennustaja keski-ikäisillä henkilöillä. Ultraäänellä määritetty kaulavaltimon IMT on kiistanalainen subkliinisen ateroskleroosin mitta, ja tuloksemme näyttivät, ettei se ennustanut tulevia SV-tapahtumia, kun riskimalli vakioitiin tavanomaisilla riskitekijöillä. Sen sijaan tuloksemme näyttivät, että ultraäänellä määritetty vatsa-aortan plakkien pituus on voimakas tulevien SV-tapahtumien ennustaja ja plakkien pituus antaa prognostista informaatiota tavanomaisten SV-riskitekijöiden lisäksi yli 20 vuo

Aims: a) To analyze the relationship of known and emerging biomarkers/indicators for early risk identification of cardiometabolic health risk; b) to identify early risk markers to be used in both clinical and nonclinical settings; and c) to propose a definition of early risk identification in terms of pre-metabolic syndrome (PreMetSyn). Data synthesis: Pubmed/Medline, Web of Science, Embase, and Cochrane were searched for Systematic Reviews and Meta-analysis. Selected studies were evaluated, and relevant data were extracted and synthesized. Conclusions: Serum uric acid is a good predictive biomarker of metabolic syndrome (MetSyn) and has been associated with non-alcoholic liver fat disease (NAFLD) and type 2 diabetes. NAFLD emerges as an early risk indicator of PreMetSyn by itself. Muscle strength should also be included as an early risk marker of cardiometabolic health. High serum triglycerides and waist circumference confirm their predictive value regarding MetSyn. Indicators related to an inflammatory/proinflammatory status usually linked to MetSyn showed limited evidence as robust biomarkers for PreMetSyn. Authors suggest defining PreMetSyn related to cardiometabolic risk. It is also necessary to determine how close people are to the cut-off point of MetSyn components, including emerging indicators proposed by our review. Some biomarkers could be used as indicators of PreMetSyn, before any of the MetSyn components appear, allowing early health interventions to prevent its development. Defining a PreMetSyn status might consider both emerging indicators and those variables already included in the definition of MetSyn. New indicators should be considered to create a new risk score specifically meant for PreMetSyn. (c) 2021 The Authors. Published by Elsevier B.V. on beh

BackgroundAdipokines have inflammatory and fibrotic properties that may be critical in interstitial lung disease (ILD). We examined associations of serum adipokine levels with CT imaging-based measures of subclinical ILD and lung function among community-dwelling adults.MethodsA subset of the original Multi-Ethnic Study of Atherosclerosis cohort (n = 1,968) had adiponectin, leptin, and resistin measured during follow-up visits (2002-2005). We used regression models to examine associations of adiponectin, leptin, and resistin levels with (1) high-attenuation areas (HAAs) from CT scans (2004-2005, n = 1,144), (2) interstitial lung abnormalities (ILAs) from CT scans (2010-2012, n = 872), and (3) FVC from spirometry (2004-2006, n = 1,446). We used -(1/HAA2), which we denoted with H, to model HAA as our outcome to meet model assumptions.ResultsHigher adiponectin was associated with lower HAA on CT imaging among adults with a BMI ≥ 25 kg/m2 (P for BMI interaction = .07). Leptin was more strongly associated with ILA among never smokers compared with ever smokers (P for smoking interaction = .004). For every 1-SD increment of log-transformed leptin, the percent predicted FVC was 3.8% lower (95% CI, -5.0 to -2.5). Higher serum resistin levels were associated with greater HAA on CT in a fully adjusted model. For every 1-SD increment of log-transformed resistin there was an increase in H of 14.8 (95% CI, 3.4-26.3).ConclusionsHigher adiponectin levels were associated with lower HAA on CT imaging among adults with a higher BMI. Higher leptin and resistin levels were associated with lower FVC and greater HAA, respectively.

Background and aims: Pediatric obesity associates with both low-grade inflammation and cardiometabolic risk on the population level. Yet on an individual patient level, overweight/obesity does not always equal increased cardiometabolic risk. In this study, we examine whether low-grade inflammation associates with cardiometabolic risk in Danish children, independent of degree of adiposity. We further assess the value of integrating multiple inflammation markers to identify children with very-high cardiometabolic risk profiles.Method and results: We studied 2192 children and adolescents aged 6-18 years from an obesity clinic cohort and a population-based cohort, in a cross-sectional study design. Anthropometry, blood pressure, pubertal stage and body composition by dual-energy X-ray absorptiometry were assessed, and biomarkers including fasting serum high sensitivity C-reactive protein (hsCRP), white blood cells (WBC), resistin, lipid profile and glucose metabolism were measured. Adjusted correlation analysis and odds ratios were calculated. We found that, independent of degree of adiposity, having high-normal inflammation marker concentrations associated with increased cardiometabolic risk: for girls, hsCRP >0.57-9.98 mg/L (mid/upper tertile) associated with similar to 2-fold higher odds of dyslipidemia and hepatic steatosis (vs. lower tertile). For both sexes, WBC >7.0-12.4 10(9) /L (upper tertile) associated with 2.5-fold higher odds of insulin resistance. Lastly, children with multiple inflammation markers in the high-normal range exhibited the most severe cardiometabolic risk profile.Conclusion: Low-grade inflammation associates with cardiometabolic risk in children independent of degree of adiposity. The associations vary with sex and inflammation marker measured. Finally, integrating multiple low-grade inflammation markers identifies a very-high-risk subgroup of children with overweight/obesity and may have clinical value. (C) 2020 The It

Background and aims: Pediatric obesity associates with both low-grade inflammation and cardiometabolic risk on the population level. Yet on an individual patient level, overweight/obesity does not always equal increased cardiometabolic risk. In this study, we examine whether low-grade inflammation associates with cardiometabolic risk in Danish children, independent of degree of adiposity. We further assess the value of integrating multiple inflammation markers to identify children with very-high cardiometabolic risk profiles.Method and results: We studied 2192 children and adolescents aged 6-18 years from an obesity clinic cohort and a population-based cohort, in a cross-sectional study design. Anthropometry, blood pressure, pubertal stage and body composition by dual-energy X-ray absorptiometry were assessed, and biomarkers including fasting serum high sensitivity C-reactive protein (hsCRP), white blood cells (WBC), resistin, lipid profile and glucose metabolism were measured. Adjusted correlation analysis and odds ratios were calculated. We found that, independent of degree of adiposity, having high-normal inflammation marker concentrations associated with increased cardiometabolic risk: for girls, hsCRP >0.57-9.98 mg/L (mid/upper tertile) associated with similar to 2-fold higher odds of dyslipidemia and hepatic steatosis (vs. lower tertile). For both sexes, WBC >7.0-12.4 10(9) /L (upper tertile) associated with 2.5-fold higher odds of insulin resistance. Lastly, children with multiple inflammation markers in the high-normal range exhibited the most severe cardiometabolic risk profile.Conclusion: Low-grade inflammation associates with cardiometabolic risk in children independent of degree of adiposity. The associations vary with sex and inflammation marker measured. Finally, integrating multiple low-grade inflammation markers identifies a very-high-risk subgroup of children with overweight/obesity and may have clinical value. (C) 2020 The It

Background: Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Methods: Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin’s concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Results: Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = − 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Conclusions: Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin’s secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.

Objectives To assess the variability and predictability of adiponectin, leptin, resistin and their ratios in non-obese and obese women with anovulatory polycystic ovary syndrome (aPCOS). Results A total of 52 ovulatory controls (mean age = 31.63 ± 4.88 years, BMI = 25.33 ± 2.68 kg/m2); 54 non-obese (mean age = 32.11 ± 4.25 years, BMI = 25.72 ± 2.95 kg/m2) and 50 obese women with aPCOS (mean age = 33.64 ± 4.14 years, BMI = 39.19 ± 2.99 kg/m2) were recruited. The aPCOS group had lower adiponectin [13.0 (10.49–16.59) vs 18.42 (15.72–19.92) µg/ml, p < 0.0001], adiponectin: leptin ratio (A:L) [0.60 (0.35–0.88) vs 1.19 (0.92–1.37), p < 0.0001], and adiponectin: resistin ratio (A:R) [0.30 (0.21–0.43) vs 0.42 (0.32–0.62), p < 0.0001] but a higher leptin [20.02 (14.54–26.80) vs 16.17 (14.51–18.36) ng/ml, p < 0.0001] and leptin: resistin ratio (L:R) [0.53 (0.37–0.82) vs 0.40 (0.27–0.48), p < 0.0001] compared to the controls. The obese aPCOS group had lower adiponectin [11.04 (5.66–13.25) vs 14.18 (11.04–18.02), p < 0.0001 and 18.42 (15.72–19.92) µg/ml, p < 0.0001], A:L [0.36 (0.27–0.44) vs 0.78 (0.61–1.16), p < 0.0001 and 1.19 (0.92–1.37), p < 0.0001], and A:R [0.24 (0.17–0.38) vs 0.40 (0.23–0.58), p < 0.0001 and 0.42 (0.32–0.62), p < 0.0001] but a higher leptin [26.80 (14.28–32.09) vs 17.95 (14.86–21.26), p < 0.05 and 16.17 (14.51–18.36) ng/ml, p < 0.0001] and L:R [0.63 (0.46–1.03) vs 0.41 (0.30–0.61), p < 0.0001 and 0.40 (0.27–0.48), p < 0.0001] compared to the non-obese aPCOS and control group, respectively. A:L showed the best discriminatory power in predicting aPCOS (AUC = 0.83), followed by adiponectin alone (AUC = 0.79), L:R and leptin alone (both AUC = 0.69). Resistin alone had the poorest discriminatory power (AUC = 0.48).

ObjectiveResistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD.MethodsThere were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause.ResultsPatients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by FMD, was significantly lower with increasing resistin quartile (I, 9.1% ± 3.3%; II, 7.1% ± 3.5%; III, 5.8% ± 4.0%; IV, 5.6% ± 3.5%; P = .002). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, -2.26 [95% conf

Objectives To assess the variability and predictability of adiponectin, leptin, resistin and their ratios in non-obese and obese women with anovulatory polycystic ovary syndrome (aPCOS). Results A total of 52 ovulatory controls (mean age = 31.63 ± 4.88 years, BMI = 25.33 ± 2.68 kg/m2); 54 non-obese (mean age = 32.11 ± 4.25 years, BMI = 25.72 ± 2.95 kg/m2) and 50 obese women with aPCOS (mean age = 33.64 ± 4.14 years, BMI = 39.19 ± 2.99 kg/m2) were recruited. The aPCOS group had lower adiponectin [13.0 (10.49–16.59) vs 18.42 (15.72–19.92) µg/ml, p < 0.0001], adiponectin: leptin ratio (A:L) [0.60 (0.35–0.88) vs 1.19 (0.92–1.37), p < 0.0001], and adiponectin: resistin ratio (A:R) [0.30 (0.21–0.43) vs 0.42 (0.32–0.62), p < 0.0001] but a higher leptin [20.02 (14.54–26.80) vs 16.17 (14.51–18.36) ng/ml, p < 0.0001] and leptin: resistin ratio (L:R) [0.53 (0.37–0.82) vs 0.40 (0.27–0.48), p < 0.0001] compared to the controls. The obese aPCOS group had lower adiponectin [11.04 (5.66–13.25) vs 14.18 (11.04–18.02), p < 0.0001 and 18.42 (15.72–19.92) µg/ml, p < 0.0001], A:L [0.36 (0.27–0.44) vs 0.78 (0.61–1.16), p < 0.0001 and 1.19 (0.92–1.37), p < 0.0001], and A:R [0.24 (0.17–0.38) vs 0.40 (0.23–0.58), p < 0.0001 and 0.42 (0.32–0.62), p < 0.0001] but a higher leptin [26.80 (14.28–32.09) vs 17.95 (14.86–21.26), p < 0.05 and 16.17 (14.51–18.36) ng/ml, p < 0.0001] and L:R [0.63 (0.46–1.03) vs 0.41 (0.30–0.61), p < 0.0001 and 0.40 (0.27–0.48), p < 0.0001] compared to the non-obese aPCOS and control group, respectively. A:L showed the best discriminatory power in predicting aPCOS (AUC = 0.83), followed by adiponectin alone (AUC = 0.79), L:R and leptin alone (both AUC = 0.69). Resistin alone had the poorest discriminatory power (AUC = 0.48).

Introduction: Psoriasis is a chronic inflammatory skin disease that is increasingly being recognized as a complex disorder affecting multiple systems. Systemic inflammation is considered the pathogenic link between psoriasis and its comorbid conditions that include arthritis, metabolic disorders, depression, and cardiovascular diseases. The presence of comorbid conditions modifies both its clinical management and the therapeutic approach in psoriatic patients. Areas covered: This review describes the clinical, epidemiological, and pathogenic link between psoriasis and obesity. Furthermore, data related to the effects of synthetic antipsoriatic drugs on obesity are collated. Expert opinion: Obesity is one of the most common comorbid conditions that is relevant both for a patient’s overall health and the clinical outcomes of antipsoriatic therapies. Indeed, some treatments of psoriasis might be impaired by adiposity. Moreover, obesity’s association with dyslipidemia, hypertension, and increased liver enzymes could further be worsened by acitretin, cyclosporine and methotrexate, respectively. Therefore, the identification of therapeutic targets whose blockade could have positive effects on both psoriasis and mechanisms regulating body weight homeostasis may be of great relevance to the treatment of patients with psoriasis.

Ishemijska bolest srca (IBS) danas predstavlja jedan od glavnih uzroka smrtnosti u svetu. U osnovi ove bolesti se nalazi ateroskleroza koja predstavlja multifaktorsko, hronično inflamatorno oboljenje indukovano ćelijskim i imunološkim odgovorom vaskularnog zida na metaboličku povredu. Humani rezistin je proinflamatorni protein, koji može imati značajnu ulogu u razvoju ateroskleroze i IBS. Ipak, kliničke studije izvedene do sada došle su do oprečnih zaključaka vezane za ulogu ovog proteina u IBS. Kako bi se doprinelo boljem razumevanju uloge rezistina u ishemijskoj bolesti srca, ciljevi ovog istraživanja su bili određivanje nivoa iRNK rezistina i njegovog receptora CAP1 u mononuklearnim ćelijama periferne krvi i koncentracija rezistina u krvi pacijenata sa IBS i zdravih ispitanika, koji su činili kontrolnu grupu (KG), ispitivanje njihove međusobne povezanosti, povezanosti sa genskom ekspresijom IL-6 i CD36 i povezanosti sa lipidnim i nelipidnim faktorima rizika za razvoj ateroskleroze. U ovu studiju uključeno je 95 pacijenata sa indikacijama za koronarnu angiografiju i 33 ZI. Nivoi iRNK ispitivanih parametara su određeni metodom qPCR-a, koncentracije rezistina ELISA metodom, a subklase lipoproteinskih čestica elektroforezom na gradijentu nedenaturišućeg poliakrilamidnog gela. Koncentracije rezistina, nivoi iRNK CAP1 i CD36 su bili značajno viši kod svih grupa pacijenata sa IBS u odnosu na KG (p<0,001; p<0,001; p<0,001, redom). Pacijenti sa akutnim koronarnim sindromom su imali značajno više koncentracije rezistina u odnosu na druge grupe pacijenata (pstabilna angina pektoris=0,028; pbez anginoznih tegoba i značajne stenoze=0,003). Nivoi iRNK rezistina se nisu značajno razlikovali između ispitivanih grupa. Pacijenti sa sadržajem malih gustih LDL (mgLDL) čestica ≥50% su imali značajno više koncentracije rezistina (p=0,031) i nivoe iRNK rezistina (p=0,004) u odnosu na pacijente sa sadržajem mgLDL čestica <50%. Nezavisni prediktori koncentracija rezistina su bili kreatin, Ischemic heart disease (IHD) is one of the major causes of morbidity and loss of quality of life across the globe. The pathogenesis of IHD lays in the development of dyslipidemia, increased proinflammatory processes and consequently atherosclerosis evolvement and progression. Human resistin is a proinflammatory cytokine, with a potential role in atherosclerosis and IHD development. However, clinical studies conducted so far have been inconsistent regarding resistin’s role in IHD. The aims of this study were to determine resistin mRNA levels and mRNA levels of resistin receptor, CAP1, in peripheral blood mononuclear cells (PBMC) and circulating resistin concentrations in IHD patients and healthy subjects (HS), to evaluate their interconnection and association with gene expression levels of IL-6 and CD36, as well as their association with lipid and non-lipid atherosclerosis risk factors. This study included 95 patients requiring coronary angiography and 33 HS. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by qPCR. LDL and HDL subclasses were determined by gradient gel electrophoresis. Plasma resistin, CAP1 and CD36 mRNA were significantly higher in all groups of IHD patients compared to HS (P<0.001; P<0.001; P<0.001, respectively). Acute coronary syndrome patients had significantly higher plasma resistin compared to other groups of patients (P=0.028; P=0.003). Resistin mRNA levels were not significantly different between any of the investigated groups. Plasma resistin (P=0.031) and resistin mRNA (P=0.004) were significantly higher in patients with the proportion of sdLDL particles ≥50%, compared to the group with the relative proportion of sdLDL particles <50%. Multiple linear regression analysis identified creatinine and total cholesterol as independent predictors of plasma resistin (adjR2=0.289); LDL particle diameter and CD36 mRNA levels of resistin mRNA (adjR2=0.192); TG and CD36 mRNA of CAP1 mRNA (adjR2=0.376); hsCRP, creatinine an

The article presents the modern literature data about the prevalence, etiology, pathogenesis of non-alcoholic fatty liver disease in type 2 diabetes mellitus, approaches to the diagnosis and therapy of these patients. The analysis of literature on the risk factors for cardiovascular diseases and cognitive impairment in patients with type 2 diabetes mellitus in non-alcoholic fatty liver disease has been carried out. The role of invasive, minimally invasive and non-invasive methods for assessing the degree of liver fibrosis is shown. The results of own researches, namely determining the features of melatonin excretion in urine and its correlation with the degree of liver fibrosis in patients with type 2 diabetes mellitus in the presence of non-alcoholic fatty liver disease, are given. The results of studying the level of adiponectin in these patients and the role of nutrient therapy to reduce the risk of cardiovascular disorders are presented., В статье представлены данные современной литературы о распространенности, этиологии и патогенезе неалкогольной жировой болезни печени (НАЖБП) при сахарном диабете (СД) 2-го типа, направлениях диагностики и терапии этих больных. Проведен анализ литературы о факторах риска сердечно-сосудистых заболеваний и когнитивных нарушений у больных СД 2-го типа при НАЖБП. Показана роль инвазивных, малоинвазивных и неинвазивных методов оценки степени фиброза печени. Приведены результаты собственных исследований, а именно определение особенностей экскреции мелатонина с мочой и ее связи со степенью фиброза печени у больных СД 2-го типа при НАЖБП. Описаны результаты изу­чения уровня адипонектина у данной категории больных и роли нутриентной терапии для снижения риска кардиоваскулярных нарушений., У роботі наведено дані сучасної літератури щодо поширеності, етіології і патогенезу неалкогольної жирової хвороби печінки (НАЖХП) за наявності цукрового діабету (ЦД) 2-го типу, напрямків діагностики і терапії цих хворих. Проведено аналіз літератури щодо чинників ризику серцево-судинних захворювань та когнітивних порушень у хворих на ЦД 2-го типу за наявності НАЖХП. Показано роль інвазивних, малоінвазивних та неінвазивних методів оцінки ступеня фіброзу печінки. Наведено результати власних досліджень, а саме визначення особливостей екскреції мелатоніну із сечею та її зв’язку із ступенем фіброзу печінки у хворих на ЦД 2-го типу за наявності НАЖХП. Описано результати вивчення рівня адипонектину у даної категорії хворих та ролі нутрієнтної терапії для зниження ризику кардіоваскулярних порушень.

ObjectiveThis study examined the associations between abdominal IMAT area and density with inflammatory markers associated with cardiometabolic disease.Methods1897 participants enrolled in the Multi-Ethnic Study of Atherosclerosis underwent computed tomography to quantify body composition and measurements of adiponectin, leptin, interleukin-6 (IL-6), C-reactive protein (CRP), and resistin.ResultsThe mean age and body mass index of participants was 65years and 28kg/m2, respectively, and 50% were female. After adjustment for age, sex, and race/ethnicity, as IMAT area increased and density decreased from the first to fourth quartile, markers of inflammation increased linearly (p<0.01). Using linear regression, and with adjustment for demographics, cardiovascular disease risk factors, and abdominal muscle area and density, a 1-standard deviation (SD) increase in total abdominal IMAT area was associated with a 21%, 36% and 20% higher IL-6, leptin, and CRP, respectively, and 19% lower adiponectin (p<0.001). With similar adjustment, a 1-SD decrease in total abdominal IMAT density was associated with a 14%, 32%, and 15% higher IL-6, leptin, and CRP, respectively, and 22% lower adiponectin (p<0.001). These associations were attenuated with the addition of visceral fat (p>0.05).ConclusionsAbdominal IMAT area and density are associated with inflammatory markers, with these associations attenuated by central adiposity.

Role of resistin in insulin sensitivity and metabolic syndrome (MetS) is controversial till date. Increased serum resistin levels are associated with MetS and insulin resistance. The aim of this study was to investigate the relationship between serum resistin levels with markers of the MetS in females. In a cross-sectional study, a total of 170 healthy female subjects were selected for the study. Out of which 71 (age 31.59 ± 4.88 years) were with MetS and 99 (age 31.75 ± 6.34 years) were without MetS. Different parameters of MetS and serum resistin level were measured according to the standard protocols as given in NCEP ATP III 2001 guideline. Serum resistin levels were significantly higher in subjects with MetS when compared with subjects without MetS [13.54 ± 4.14 ng/ml (n = 71) vs. 7.42 ± 2.31 ng/ml (n = 99); P ≤ 0.001]. Resistin levels were positively associated with waist circumference, systolic and diastolic blood pressure, plasma glucose, waist/hip ratio, serum triglycerides, serum cholesterol, serum VLDL, plasma insulin, and insulin resistance, while it was negatively associated with highdensity lipoprotein. This study demonstrates a positive correlation between resistin and factors of MetS except high-density lipoprotein which was found to be negatively correlated in Indian female subjects.

Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor of IDD, is now increasingly being recognized as a systemic inflammatory state with adipokines being postulated as likely inflammatory mediators. The aim of this review was to summarize the current literature regarding the inflammatory role of adipokines in the pathophysiology of IDD. A systematic literature search was performed using the OVID Medline, EMBASE and PubMed databases to identify all studies assessing IDD and adipokines. Fifteen studies were included in the present review. Leptin was the most commonly assessed adipokine. Ten of 15 studies were conducted in humans; three in rats and two in both humans and rats. Studies focused on a variety of topics ranging from receptor identification, pathway analysis, genetic associations, and proteonomics. Currently, data from both human and animal experiments demonstrate significant effects of leptin and adiponectin on the internal milieu of intervertebral discs. However, future studies are needed to determine the molecular pathway relationships between adipokines in the pathophysiology of IDD as avenues for future therapeutic targets.

Resistin-like molecules (RELM), a family of mammalian-conserved secreted proteins, have immunoregulatory effects in helminth infection, acting as a negative feedback loop to limit excess inflammation at the expense of increased parasite burden. This is through downregulation of the Th2 cytokines, IL-4 and IL-13, that are essential for alternative activation of macrophages and clearance of helminths. However, it is unclear how the human RELM proteins regulate immunity to helminth infections and inflammation. In this thesis, we have combine data from human studies and a transgenic mouse model, where human resistin and its regulatory region was inserted in mice (hRetnTg+). Human patients infected with filarial nematodes or soil-transmitted helminths had higher levels of circulating hResistin, and hResistin was associated with higher parasite burden. To assess whether hResistin directly increases helminth infection, we infected hRetnTg+ mice with the murine hookworm, Nippostrongylus brasiliensis (Nb), which revealed that hResistin is upregulated by macrophages and we identified IL-4/STAT6 signaling as a novel pathway for hResistin expression. Human resistin expression during helminth infection contributes to increased parasite burden and prolonged infection. RNA-seq of whole lung RNA demonstrated that hRetnTg+ mice had increase proinflammatory cytokines and toll-like receptor (TLR) signaling. In human patients infected with helminths, hResistin is correlated with proinflammatory cytokines, suggesting that hResistin contributes to increased helminth infection through the upregulation of Th1 cytokines. Structural interaction predictions revealed that hResistin binds to TLR4 in the same binding pocket as MD-2, the adaptor protein that mediates lipopolysaccharide(LPS)-TLR4 interaction. Given that LPS-TLR4 interaction initiates septic shock, we hypothesized that hResistin may protect the host from endotoxic shock by outcompeting LPS binding to TLR4 and blocking subsequent pr

Background: Polycystic ovary syndrome (PCOS) is associated with features linked to metabolic syndrome including visceral obesity, dyslipidemia and impaired glucose homeostasis. Recent studies suggest that these metabolic effects are linked to a low-grade chronic inflammation with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle. Adipose tissue produces immunomodulatory adipocytokines which contribute to regulation of insulin sensitivity, reproduction and cardiovascular function. Limited evidence is available on the role of adipocytokines in PCOS. Aim(s): This study investigated the relationships between PCOS status, adipocytokines and aetiological features of PCOS. Method(s): In an observational study of community recruited PCOS and controls, we measured serum HMW-adiponectin, omentin, resistin, interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), plasminogen activator inhibotir-1(PAI-1), high sensitivity CRP (hs-CRP), androgens, SHBG, fasting glucose and insulin levels. Result(s): Forty-nine women with PCOS (age 29.8 +/- 5.9 years, BMI: 29.0 +/- 5.4 kg/m2) and 25 healthy controls (age 37.6 +/- 7.8 years, BMI: 28.9 +/- 4.0 kg/m2) were recruited. Homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.006), free androgen index (FAI) (P = 0.01) and Ferriman-Galway score (P < 0.001) were higher in PCOS. For adipocytokines, women with PCOS had lower omentin [median (IQR): 68.76(67.17) vs 112.45(67.42)] (P = 0.01) and higher hs-CRP [median (IQR): 2.15 (3.4) vs 1.00 (2.1)] (P = 0.03) after adjustment for age and BMI. On assessment of non-obese and obese subgroups, HMWadiponectin and omentin were lower in obese women with PCOS compared to obese controls (P = 0.022 and P = 0.034 respectively) and nonobese PCOS (P = 0.028 and P = 0.016 respectively). Among women with PCOS, HMW-adiponectin was negatively correlated with HOMA-IR and FAI, however only the correlation between HMW-adiponectin and FAI

Background: Polycystic ovary syndrome (PCOS) is associated with features linked to metabolic syndrome including visceral obesity, dyslipidemia and impaired glucose homeostasis. Recent studies suggest that these metabolic effects are linked to a low-grade chronic inflammation with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle. Adipose tissue produces immunomodulatory adipocytokines which contribute to regulation of insulin sensitivity, reproduction and cardiovascular function. Limited evidence is available on the role of adipocytokines in PCOS. Aim(s): This study investigated the relationships between PCOS status, adipocytokines and aetiological features of PCOS. Method(s): In an observational study of community recruited PCOS and controls, we measured serum HMW-adiponectin, omentin, resistin, interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), plasminogen activator inhibotir-1(PAI-1), high sensitivity CRP (hs-CRP), androgens, SHBG, fasting glucose and insulin levels. Result(s): Forty-nine women with PCOS (age 29.8 +/- 5.9 years, BMI: 29.0 +/- 5.4 kg/m2) and 25 healthy controls (age 37.6 +/- 7.8 years, BMI: 28.9 +/- 4.0 kg/m2) were recruited. Homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.006), free androgen index (FAI) (P = 0.01) and Ferriman-Galway score (P < 0.001) were higher in PCOS. For adipocytokines, women with PCOS had lower omentin [median (IQR): 68.76(67.17) vs 112.45(67.42)] (P = 0.01) and higher hs-CRP [median (IQR): 2.15 (3.4) vs 1.00 (2.1)] (P = 0.03) after adjustment for age and BMI. On assessment of non-obese and obese subgroups, HMWadiponectin and omentin were lower in obese women with PCOS compared to obese controls (P = 0.022 and P = 0.034 respectively) and nonobese PCOS (P = 0.028 and P = 0.016 respectively). Among women with PCOS, HMW-adiponectin was negatively correlated with HOMA-IR and FAI, however only the correlation between HMW-adiponectin and FAI

BackgroundAdenylate cyclase-associated protein 1 (CAP1) is a recently identified receptor for human resistin. As resistin has been related to CAD development and progression and CAP1 has never been evaluated in CAD, the aim of this study was to determine its peripheral blood mononuclear cells (PBMCs) mRNA in patients with CAD, and resistin plasma concentration, PBMCs resistin and CD36 mRNA, considering resistis ability to stimulate CD36 expression invitro. Materials and methodsThis case-controlled study included 27 healthy subjects (CG) and 66 patients requiring coronary angiography. Of the latter, 42 had nonsignificant CAD whereas 24 had significant CAD. Circulating resistin was measured by ELISA; PBMCs CAP1, resistin and CD36 mRNA were determined by real-time PCR. ResultsPatients with significant as well as patients with nonsignificant CAD had significantly higher resistin concentrations compared to the CG (P lt 0 lt bold> lt /bold>001; P=0 lt bold> lt /bold>003). Resistin mRNA did not show significant difference between the investigated groups. CAP1 and CD36 mRNA were significantly higher in significant CAD (P lt 0 lt bold> lt /bold>001; P lt 0 lt bold> lt /bold>001, respectively) and nonsignificant CAD (P lt 0 lt bold> lt /bold>001; P lt 0 lt bold> lt /bold>001, respectively) compared to the CG; significant CAD showed significantly higher CD36 mRNA (P=0 lt bold> lt /bold>040) compared to the nonsignificant CAD group. Multiple linear regression analysis identified Tg and CD36 mRNA as independent predictors of CAP1 (R-2=0 lt bold> lt /bold>402; adjR(2)=0 lt bold> lt /bold>376). ConclusionSignificant up-regulation of PBMCs CAP1, CD36 mRNA and plasma resistin found in significant CAD, as well as in nonsignificant CAD compared to CG, indicates that resistin could be able to exert its effects stronger on cells with up-regulated CAP1 mRNA thus contributing atherosclerosis development.

Resistin-like molecules (RELM), a family of mammalian-conserved secreted proteins, have immunoregulatory effects in helminth infection, acting as a negative feedback loop to limit excess inflammation at the expense of increased parasite burden. This is through downregulation of the Th2 cytokines, IL-4 and IL-13, that are essential for alternative activation of macrophages and clearance of helminths. However, it is unclear how the human RELM proteins regulate immunity to helminth infections and inflammation. In this thesis, we have combine data from human studies and a transgenic mouse model, where human resistin and its regulatory region was inserted in mice (hRetnTg+). Human patients infected with filarial nematodes or soil-transmitted helminths had higher levels of circulating hResistin, and hResistin was associated with higher parasite burden. To assess whether hResistin directly increases helminth infection, we infected hRetnTg+ mice with the murine hookworm, Nippostrongylus brasiliensis (Nb), which revealed that hResistin is upregulated by macrophages and we identified IL-4/STAT6 signaling as a novel pathway for hResistin expression. Human resistin expression during helminth infection contributes to increased parasite burden and prolonged infection. RNA-seq of whole lung RNA demonstrated that hRetnTg+ mice had increase proinflammatory cytokines and toll-like receptor (TLR) signaling. In human patients infected with helminths, hResistin is correlated with proinflammatory cytokines, suggesting that hResistin contributes to increased helminth infection through the upregulation of Th1 cytokines. Structural interaction predictions revealed that hResistin binds to TLR4 in the same binding pocket as MD-2, the adaptor protein that mediates lipopolysaccharide(LPS)-TLR4 interaction. Given that LPS-TLR4 interaction initiates septic shock, we hypothesized that hResistin may protect the host from endotoxic shock by outcompeting LPS binding to TLR4 and blocking subsequent pr

Helminths trigger multiple immunomodulatory pathways that can protect from sepsis. Human resistin (hRetn) is an immune cell-derived protein that is highly elevated in helminth infection and sepsis. However, the function of hRetn in sepsis, or whether hRetn influences helminth protection against sepsis, is unknown. Employing hRetn-expressing transgenic mice (hRETNTg+) and recombinant hRetn, we identify a therapeutic function for hRetn in lipopolysaccharide (LPS)-induced septic shock. hRetn promoted helminth-induced immunomodulation, with increased survival of Nippostrongylus brasiliensis (Nb)-infected hRETNTg+ mice after a fatal LPS dose compared with naive mice or Nb-infected hRETNTg- mice. Employing immunoprecipitation assays, hRETNTg+Tlr4-/- mice, and human immune cell culture, we demonstrate that hRetn binds the LPS receptor Toll-like receptor 4 (TLR4) through its N terminal and modulates STAT3 and TBK1 signaling, triggering a switch from proinflammatory to anti-inflammatory responses. Further, we generate hRetn N-terminal peptides that are able to block LPS proinflammatory function. Together, our studies identify a critical role for hRetn in blocking LPS function with important clinical significance in helminth-induced immunomodulation and sepsis.

In the last two decades, perceptions about the role of body fat have changed. Adipocytes modulate endocrine and immune homeostasis by synthesizing hundreds of hormones, known as adipocytokines. Many studies have been investigating the influences and effects of these adipocytokines and suggest that they are modulated by the nutritional and immunologic milieu. Kidney transplant recipients (KTRs) are a unique and relevant population in which the function of adipocytokines can be examined, given their altered nutritional and immune status and subsequent dysregulation of adipocytokine metabolism. In this review, we summarize the recent findings about four specific adipocytokines and their respective roles in KTRs. We decided to evaluate the most widely described adipocytokines, including leptin, adiponectin, visfatin and resistin. Increasing evidence suggests that these adipocytokines may lead to cardiovascular events and metabolic changes in the general population and may also increase mortality and graft loss rate in KTRs. In addition, we present findings on the interrelationship between serum adipocytokine levels and nutritional and immunologic status, and mechanisms by which adipocytokines modulate morbidity and outcomes in KTRs.

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.

The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin.

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.

In the last two decades, perceptions about the role of body fat have changed. Adipocytes modulate endocrine and immune homeostasis by synthesizing hundreds of hormones, known as adipocytokines. Many studies have been investigating the influences and effects of these adipocytokines and suggest that they are modulated by the nutritional and immunologic milieu. Kidney transplant recipients (KTRs) are a unique and relevant population in which the function of adipocytokines can be examined, given their altered nutritional and immune status and subsequent dysregulation of adipocytokine metabolism. In this review, we summarize the recent findings about four specific adipocytokines and their respective roles in KTRs. We decided to evaluate the most widely described adipocytokines, including leptin, adiponectin, visfatin and resistin. Increasing evidence suggests that these adipocytokines may lead to cardiovascular events and metabolic changes in the general population and may also increase mortality and graft loss rate in KTRs. In addition, we present findings on the interrelationship between serum adipocytokine levels and nutritional and immunologic status, and mechanisms by which adipocytokines modulate morbidity and outcomes in KTRs.

The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin.

Background: Aortic stenosis (AS) is considered as an atherosclerotic related process. However, there are uncertainties whether AS in the elderly is associated with the same pathophysiological processes as in younger patients. We hypothesized that the metabolic determinants of the valvular inflammatory and calcifying processes occurring in elderly patients are different from those observed earlier in life. Methods: Among 114 patients operated for a severe AS, a complete plasma lipid blood profile and plasma levels of adipokines (resistin, leptin) were determined. The calcium content of the aortic valve was measured and valvular inflammation was quantified. Results Elderly patients (= 70 years) had significantly lower LDL-C ( p = 0.02), lower LDL-C associated with small size particles (LDL-C < 255 Å) ( p = 0.003), and higher HDL peak particle size than younger patients ( p = 0.03). In addition, elderly patients had increased plasma leptin ( p = 0.04) and resistin ( p = 0.0004) levels compared to the middle-aged group (< 70 years). In the elderly patients, higher plasma resistin blood levels were associated with increased valve calcium content and inflammation. Conclusion: The lipid profile of elderly patients was found less atherogenic than that of middle-aged patients. On the other hand, older patients with AS had higher plasma level of resistin which was associated with the degree of valvular calcification and inflammation. These results suggest that, beyond lipid model of atherosclerosis, age-related processes affecting resistin blood levels may also be involved in the late development of AS.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated imm

To explore the relationship between leptin and resistin content in plasma and parameters of ambulatory blood pressure monitoring (ABPM) in patients with diabetes mellitus (DM) type 2 and arterial hypertension (AH) I and II degree and without hypertension.The study involved 137 patients with type 2 diabetes with hypertension I and II degree and without hypertension (72 women and 65 men). Patients with type 2 DM and AH were 1st group (n=51, mean age=53,32±0,77, BMI=32,14±0,78 kg/m2), and patients with type 2 DM without AH - 2nd group (n=86, mean age=52,79±0,69, BMI=30,31±0,62 kg/m2). Control group consisted of 32 practically healthy individuals, including 16 women and 16 men (mean age=51,00±0,97, BMI=30,77±1,17 kg/m2). The groups were comparable by age and BMI (P>0.05). All patients underwent clinical and laboratory examination and ABPM. The level of leptin in the blood plasma of patients in two groups and the control one was not statistically different (p>0.05). Instead, resistin content was the highest in patients with type 2 DM and AH, the lowest – in the control group (4,51±0,34 υ 2,64±0,20 ng/ml, p=0.0007); also differed significantly in the 1st and 2nd groups of patients (p=0.0009). The distribution of patients depending on the daily profile of AH (Dipper, Non-dipper, Night-peaker) found no significant changes in the contents of leptin in patients with type 2 DM with AH or without AH. Resistin level was significantly higher in all groups of patients with type 2 DM and AH with different types of daily profile as compared to the groups without AH (p<0.05). In the group of patients with type 2 DM and AH changesin levels of resistin differed significantly in non-dipper and night-peaker groups (p=0.01).Relationship between leptin levels in plasma and ABPM parameters in patients with type 2 diabetes were not set. Instead, resistin levels in blood plasma can be considered as a prognostic marker of cardiovascular disease, including hypertension, in patients wit

Introduction: Childhood obesity is related to cardiovascular diseases and diabetes mellitus type 2 in later life. Resistin, an adipokine primarily secreted by monocytes and tissue macrophages in humans, is considered to be associated with these conditions. The Aim: To examine the correlations between resistin concentration and anthropometric parameters, lipid status, inflammatory markers and parameters of insulin resistance in obese children and adolescents. Material and Methods: The study included 66 patients (40 boys, 26 girls), which underwent anthropometric measuring and laboratory testing (glucose level, total cholesterol, high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol), triglycerides, uric acid, high-sensitivity C-reactive protein (hsCRP) and glycosylated hemoglobin (HbA1c). Insulin resistance was estimated with HOMA-IR (homeostasis model assessment of insulin resistance). Results: We determined that 63.3% of our patients had dyslipidemia, while hsCRP and uric acid levels suggested an ongoing inflammation. We established that there was a correlation between resistin concentration and waist to hip ratio (WHR) (r=0.294, p lt 0.05), as well as between resistin concentration and HOMA-IR (r=0.293, p lt 0.05). Also, uric acid levels correlated with obesity parameters. While comparing parameters by gender we found a significant difference in height (p lt 0.01), WHR (p lt 0.001), uric acid levels (p lt 0.01) and HOMA-IR (p lt 0.01). Conclusion: Our results show a link between obesity, inflammation and dyslipidemia in children and adolescents. In the future, resistin could become a significant clinical marker for evaluation of cardiometabolic risk., Uvod: Gojaznost u dečjem uzrastu se povezuje sa razvojem kardiovaskularnih bolesti i tipa 2 dijabetes melitusa u kasnijem dobu. Smatra se da je rezistin, adipokin kojeg u humanom organizumu luče monociti i tkivne makrofage, povezan sa ovim poremećajima. Cilj: Ispitati povezanost koncentracije rezistina kod gojazne dece i adolescenata sa antropometrijskim parametrima gojaznosti, lipidnim statusom, inflamatornim markerima i parametrima insulinske rezistencije. Materijal i metode: U istraživanju je učestvovalo 66 ispitanika (40 dečaka, 26 devojčica) kojima su izvršena antropometrijska merenja i laboratorijska ispitivanja (koncentracije glukoze, ukupnog holesterola, holesterola u česticama lipoproteina visoke gustine (eng. high-density lipoprotein, HDL) i niske gustine (eng. low-density lipoprotein, LDL), triglicerida, mokraćne kiseline, visokoosetljivog C-reaktivnog proteina (high-sensitivity C-reactive protein; hsCRP) i glikoziliranog hemoglobina (HbA1c)). Insulinska rezistencija je procenjena na osnovu modela za izračunavanje indeksa insulinske rezistencije (eng. homeostasis model assessment of insulin resistance; HOMA-IR). Rezultati: Kod 63,3% ispitanika utvrdili smo prisutnu dislipidemiju, a dobijene vrednosti hsCRP i mokraćne kiseline ukazuju na prisustvo inflamacije. Utvrdili smo korelaciju između koncentracije rezistina i odnosa obima struka i kukova (r=0,294, p lt 0,05) i između koncentracije rezistina i HOMA-IR (r=0,293, p lt 0,05). Ustanovili smo povezanost koncentracije mokraćne kiseline i parametara gojaznosti. Upoređivanjem parametara između polova, značajna razlika postoji u telesnoj visini (p lt 0,01), odnosu obima struka i kukova (p lt 0,001), mokraćnoj kiselini (p lt 0,01) i HOMA-IR (p lt 0,01). Zaključak: Naši rezultati ukazuju na povezanost gojaznosti, inflamacije i dislipidemije kod dece i adolescenata. Rezistin bi u budućnosti mogao biti značajan za procenu kardiometaboličkog rizika u ovoj populaciji.

ObjectiveTo describe the relationship between circulating resistin levels and cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort.Methods and resultsWe studied 1913 participants from the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels. Absolute proportions experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and all-cause death were calculated for each quartile of resistin. We used adjusted Cox proportional regression modeling resistin as a continuous variable per standard deviation of log-transformed resistin and secondarily as a categorical variable using resistin quartiles. Results were stratified by sex and race/ethnicity. The mean age of the population was 64.5 ± 10 years with half being female and a median resistin concentration of 15.1 ng/mL (11.9-19.1). Mean follow-up time was 7.2 ± 1.8 years. There was a graded increase in the occurrence of all outcomes across increasing quartiles of resistin. Modeled as a continuous variable, after adjustment for anthropomorphic measures, traditional risk factors, markers of inflammation, and other adipokines, significant associations were noted for HF (HR 1.4, CI 1.0-2.0), hard and all CVD (HR 1.3, 1.1-1.7 and 1.3, 1.1-1.6, respectively), and CHD (HR 1.31, 1.0-1.6), but not for AF or death. Significant interaction terms were noted between resistin and race, with Hispanic race/ethnicity showing the strongest relationship between resistin and outcomes.ConclusionsIn an ethnically diverse population without known CVD at baseline, there was a strong, independent association between higher resistin levels and incident CVD, CHD and HF.