Plasma Carboxy-Terminal Provasopressin (Copeptin): A Novel Marker of Insulin Resistance and Metabolic Syndrome

Context: Stress-mediated hypothalamic-pituitary-adrenal axis activation, regulated by arginine vasopressin (AVP), may have a role in the pathophysiology of metabolic syndrome (MetSyn). Objective: The objective of the study was to investigate whether plasma C-terminal provasopressin fragment (copeptin), a surrogate for circulating AVP, was associated with measures of insulin resistance and presence of MetSyn. Design, Setting, and Participants: This was a multicenter, community-based study, investigating novel biomarkers for vascular disease. Participants included 1293 African-Americans (AA) (64 ± 9 yr) and 1197 non-Hispanic whites (NHW) (59 ± 10 yr) belonging to hypertensive sibships. Main Outcome Measures: Plasma copeptin levels were measured by an immunoluminometric assay. MetSyn was defined per Adult Treatment Panel III criteria. Generalized estimating equations were used to assess whether plasma copeptin was associated with measures of insulin resistance and MetSyn. Results: The prevalence of MetSyn was 50% in AA and 49% in NHW. In each group, after adjustment for age and sex, plasma copeptin levels significantly correlated with body mass index, fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance, triglycerides, and (inversely) high-density lipoprotein cholesterol (P < 0.05 for each variable). In multivariable logistic regression models that adjusted for age, sex, smoking, statin use, serum creatinine, education, physical activity, and diuretic use, plasma copeptin levels in the highest quartile were associated with an increased odds ratio of having MetSyn compared with bottom quartile: odds ratio (95% confidence interval) in AA, 2.07 (1.45–2.95); in NHW, 1.74 (1.21–2.5). Conclusions: Our findings indicate a novel cross-sectional association between plasma copeptin and measures of insulin resistance and MetSyn.

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Associations of resistin with inflammatory and fibrinolytic markers, insulin resistance, and metabolic syndrome in middle-aged and older Chinese

Acta Endocrinologica ◽

10.1530/eje-08-0427 ◽

2008 ◽

Vol 159 (5) ◽

pp. 585-593 ◽

Cited By ~ 37

Author(s):

Qibin Qi ◽

Jing Wang ◽

Huaixing Li ◽

Zhijie Yu ◽

Xingwang Ye ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Plasminogen Activator Inhibitor ◽

Population Based ◽

Model Assessment ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Factor Α

ObjectiveResistin increases insulin resistance (IR) in mice. However, the role of resistin in human disease remains controversial. We aimed to assess plasma resistin levels and their associations with inflammatory and fibrinolytic markers, IR and metabolic syndrome (MetS) among Chinese.Design and methodsPlasma resistin was measured in a population-based cross-sectional survey of 3193 Chinese aged from 50 to 70 years in Beijing and Shanghai.ResultsThe median resistin concentration was 8.60 ng/ml (interquartile range, 5.78–14.00) among all participants, and it was higher in women than in men (P=0.008). Resistin was correlated weakly with body mass index, waist circumference, high-density lipoprotein (HDL) cholesterol (negatively), homeostatic model assessment of IR and tumor necrosis factor-α receptor 2 (TNFR2; r=0.04, 0.07, –0.09 and 0.06 respectively, all P<0.05), and more highly with C-reactive protein (CRP), interleukin (IL)6 and plasminogen activator inhibitor (PAI)1 (r=0.12, 0.12 and 0.21 respectively, all P<0.001), but only HDL cholesterol, CRP, IL6, TNFR2, and PAI1 remained significantly associated with resistin in multiple regression analysis (all P<0.05). Furthermore, elevated resistin levels were associated with the higher prevalence of IR and MetS. However, the significant relationships disappeared after adjustment for inflammatory and fibrinolytic markers especially PAI1.ConclusionsThis study suggests that resistin is more strongly associated with inflammatory and fibrinolytic markers than with obesity or IR status. The associations of resistin with IR and MetS could largely be explained by inflammatory and fibrinolytic markers especially PAI1 levels.

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Elevated Retinol-Binding Protein 4 Levels Are Associated with Metabolic Syndrome in Chinese People

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1219 ◽

2007 ◽

Vol 92 (12) ◽

pp. 4827-4834 ◽

Cited By ~ 145

Author(s):

Qibin Qi ◽

Zhijie Yu ◽

Xingwang Ye ◽

Feng Zhao ◽

Ping Huang ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Odds Ratio ◽

Large Scale ◽

Density Lipoprotein ◽

Retinol Binding Protein ◽

Model Assessment ◽

Retinol Binding Protein 4 ◽

Homeostatic Model Assessment ◽

Homeostatic Model

Abstract Context: High retinol-binding protein 4 (RBP4) is thought to be associated with insulin resistance in humans. However, evidence from large-scale populations about the relationship between RBP4 and metabolic diseases is scarce. Objective: We evaluated plasma RBP4 distribution and its association with metabolic syndrome (MetS) among middle-aged and older Chinese. Research Design and Methods: We evaluated plasma RBP4 in a cross-sectional sample of 3289 Chinese aged from 50 to 70 yr in Beijing and Shanghai by using an in-house developed and validated sandwich ELISA. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. Results: RBP4 levels were higher in male and Beijing residents, compared with female and Shanghai participants (both P < 0.001). RBP4 levels were associated positively with body mass index, waist circumference, triglycerides, total and low-density lipoprotein cholesterol, blood pressure, fasting insulin, and homeostatic model assessment of insulin resistance and negatively with high-density lipoprotein cholesterol and adiponectin (all P < 0.001). In the highest RBP4 quartile, the MetS risk was significantly higher (odds ratio 2.58; 95% confidence interval 2.08–3.20) than in the lowest quartile after adjustment for potential confounders. This association remained strong (odds ratio 2.25; 95% confidence interval 1.72–2.94) after further controlling for C-reactive protein, adiponectin, homeostatic model assessment of insulin resistance, and body mass index. Conclusions: This first large-scale population study shows that elevated RBP4 levels are strongly and independently associated with MetS. Prospective studies are needed to establish the role of RBP4 in the development of MetS and related diseases.

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Insulin Resistance and Its Association with Metabolic Syndrome in Korean Children

BioMed Research International ◽

10.1155/2017/8728017 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Jinkyung Cho ◽

Haeryun Hong ◽

Soohyun Park ◽

Shinuk Kim ◽

Hyunsik Kang

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Fat ◽

Density Lipoprotein ◽

Cross Sectional Study ◽

Healthy Children ◽

Model Assessment ◽

Fat Percentage ◽

Cross Sectional ◽

Korean Children

Background. This study investigated the association between insulin resistance (IR) and metabolic syndrome (MetS) in children. Methods. A cross-sectional study involving 1036 healthy children aged between 7 and 13 years was conducted. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an index of IR. Participants were classified according to the HOMA-IR quartiles. Results. Incremental, linear trends were found in age (p<0.001), body mass index (BMI) (p<0.001), body fat (p<0.001), waist circumference (p<0.001), resting blood pressures (BP) (p<0.001), triglycerides (TG) (p<0.001), total cholesterol (TC) (p<0.001), high density lipoprotein-cholesterol (HDL-C) (p<0.001), FBG (p<0.001), and insulin (<0.001) according to incremental HOMA-IR categories (from the 1st to 4th quartile). Compared with children in the 1st HOMA-IR quartile, children in the 4th HOMA-IR quartile had significantly higher odd ratios (ORs) of abnormalities in systolic (p=0.051) and diastolic BP (p=0.005), FBG (p<0.001), TG (p<0.001), TC (p=0.016), and HDL-C (p=0.006) even after adjustments for age, gender, BMI, and body fat percentage. Children in the 3rd HOMA-IR quartile had significant abnormalities in FBG (p<0.001), TG (p=0.001), and HDL-C (p=0.010) even after adjustments for the covariates. Conclusion. The current findings suggest that IR is significantly associated with the clustering of MetS risk factors in children in Korea.

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SAT-656 Both Neutrophil and Monocyte Ratios to High Density Lipoprotein Cholesterol Are Superior Biomarkers of Metabolic Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.277 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Neeraj Ramakrishnan ◽

Ganesh Jialal ◽

Ishwarlal Jialal

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

High Density Lipoprotein ◽

Density Lipoprotein ◽

High Density ◽

Model Assessment ◽

Roc Curve Analysis ◽

Cross Sectional ◽

Effective Measure ◽

Anti Inflammatory

Abstract Metabolic Syndrome (MetS) continues to be a significant problem globally, affecting nearly 35% of adults in the USA. Whilst there is no ideal biomarker that captures this disorder high sensitivity C-reactive protein (hsCRP) is the most widely accepted measure.We examined the ratios between the phagocytes, neutrophils(PMN)and monocytes, to high density lipoprotein (HDL) and adiponectin, two anti-inflammatory proteins, in patients with nascent MetS without the confounding of T2DM, ASCVD, smoking or lipid therapy to determine if they were valid biomarkers of MetS. Patients with nascent MetS(n=58) and matched controls(n=44) were recruited from Sacramento County. Patients with diabetes, cardiovascular diseases, inflammation (hsCRP >10mg/L or leukocytosis), smoking, anti-inflammatory and hypolipidemic drug therapies were excluded. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipid profile, insulin adiponectin, leptin and chemerin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin levels. Ratios of PMN and monocytes to HDL-C and Adiponectin were calculated and compared statistically. PMN: HDL-C and Monocyte: HDL-C, increased in patients with MetS compared to controls (p<0.0001 and p=0.001 respectively).Also the PMN: Adiponectin and monocyte: Adiponectin ratios were significantly increased in MetS (p=0.006 and 0.02 respectively). All ratios increased with increasing severity of MetS (p=0.01). Receiver Operating Characteristic (ROC) curve analysis showed that both the PMN/HDL-C and monocyte: HDL-C area under the curve(AUC)(0.85 and 0.84 respectively) significantly added to the CRP AUC(0.75), p=0.01 for both. Neither leukocyte: Adiponectin AUC was significant compared to hsCRP. Also both ratios to HDL-C correlated with cardio-metabolic features of MetS, hsCRP and insulin resistance(HOMA-IR) (p<0.05). Whilst the PMN:HDL-C ratio correlated with leptin, and chemerin the monocyte: HDL-C ratio correlated significantly with chemerin only (p<0.05) Our cross-sectional study indicates that ratios of neutrophils and monocytes to HDL-C are significantly increased in patients with nascent MetS, increase with severity of MetS, correlate positively with inflammation and insulin resistance and both ratios appear to be better predictors of MetS than hsCRP. In conclusion, they provide a cost-effective measure of Metabolic Syndrome and should be confirmed in larger data bases and prospective studies.

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Investigating the relationship between insulin resistance and adipose tissue in a randomized Tehrani population

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2020-0084 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Jalaledin Mirzay Razzaz ◽

Hossein Moameri ◽

Zahra Akbarzadeh ◽

Mohammad Ariya ◽

Seyed ali Hosseini ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Body Fat ◽

Odds Ratio ◽

Cross Sectional Study ◽

Model Assessment ◽

Fasting Insulin ◽

Cross Sectional ◽

Body Fat Percent ◽

The Relationship

Abstract Objectives Insulin resistance is the most common metabolic change associated with obesity. The present study aimed to investigate the relationship between insulin resistance and body composition especially adipose tissue in a randomized Tehrani population. Methods This study used data of 2,160 individuals registered in a cross-sectional study on were randomly selected from among subjects who were referred to nutrition counseling clinic in Tehran, from April 2016 to September 2017. Insulin resistance was calculated by homeostasis model assessment formula. The odds ratio (95% CI) was calculated using logistic regression models. Results The mean age of the men was 39 (±10) and women were 41 (±11) (the age ranged from 20 to 50 years). The risk of increased HOMA-IR was 1.03 (95% CI: 1.01–1.04) for an increase in one percent of Body fat, and 1.03 (95% CI: 1.00–1.05) for an increase in one percent of Trunk fat. Moreover, the odds ratio of FBS for an increase in one unit of Body fat percent and Trunk fat percent increased by 1.05 (adjusted odds ratio [95% CI: 1.03, 1.06]) and 1.05 (95% CI: 1.02, 1.08). Also, the risk of increased Fasting Insulin was 1.05 (95% CI: 1.03–1.07) for an increase in one unit of Body fat percent, and 1.05 (95% CI: 1.02–1.08) for an increase in one unit of Trunk fat percent. Conclusions The findings of the present study showed that there was a significant relationship between HOMA-IR, Fasting blood sugar, Fasting Insulin, and 2 h Insulin with percent of Body fat, percent of Trunk fat.

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Insulin resistance in PLHIV on HAART and HAART naïve PLHIV: A Cross-sectional Study

10.36106/ijar/3506686 ◽

2020 ◽

pp. 1-3

Author(s):

Prabir Kumar Ganguly ◽

Niladri Das

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Antiretroviral Therapy ◽

Cross Sectional Study ◽

Metabolic Effects ◽

People Living With Hiv ◽

Model Assessment ◽

Sectional Study ◽

Cross Sectional ◽

Group I

ABSTRACT HAART (Highly active antiretroviral therapy) has transformed a fatal disease to a chronic, manageable disease. But long term toxicities are emerging after prolonged exposure to antiretroviral therapy(ART). Adverse metabolic effects like dyslipidemia, increased blood pressure, and insulin resistance(IR) have been attributed to HAART. Therefore, the use of HAART raises concerns regarding metabolic disorders and cardiovascular risk in HIV(Human immunodeficiency virus) infected patients. Objective: To determine the prevalence of insulin resistance in a cohort of HIV infected patients on HAART as compared to HAART naïve PLHIV(People living with HIV) Methods: A cross sectional study includes 53 subjects, out of which 26 were PLHIV on ART –Group I, 27 were ART naïve PLHIV-Group II was conducted. Insulin resistance was determined by homeostasis model assessment (HOMA-IR) mathematical model. Statistical analysis was performed to assess the association between demographic, clinical characteristics, laboratory results and insulin resistance. Results: 69.5 % PLHIV on HAART showed IR, as compared to 37 % of ART naïve PLHIV (p= 0.01). MetS(Metabolic Syndrome) was found in 53.8% among PLHIV on ART , compared to 11.1% among ART naïve PLHIV(p= 0.001) .In the multivariate analysis, presence of metabolic syndrome was found to be directly associated with insulin resistance.

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Parental PM2.5 Exposure-Promoted Development of Metabolic Syndrome in Offspring Is Associated With the Changes of Immune Microenvironment

Toxicological Sciences ◽

10.1093/toxsci/kfz109 ◽

2019 ◽

Vol 170 (2) ◽

pp. 415-426 ◽

Cited By ~ 2

Author(s):

Jia Zhang ◽

Xuejiao Zeng ◽

Xihao Du ◽

Kun Pan ◽

Liying Song ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Fine Particulate Matter ◽

Density Lipoprotein ◽

Model Assessment ◽

Immune Microenvironment ◽

Male And Female ◽

Female Mice ◽

Parental Exposure ◽

Pm2.5 Exposure

Abstract Parental exposure to ambient fine particulate matter (PM2.5) has been associated with some of adverse health outcomes in offspring. The association between parental PM2.5 exposure and the development of metabolic syndrome (MetS) in offspring, and the effects of parental PM2.5 exposure on the susceptibility of offspring mice to PM2.5, has not been evaluated. The C57BL/6 parental mice (male and female mice) were exposed to filtered air (FA) or concentrated PM2.5 (PM) using Shanghai-METAS for a total of 16 weeks. At week 12 during the exposure, we allowed the parental male and female mice to breed offspring mice. The male offspring mice were divided into 4 groups and exposed to PM and FA again. The results showed that whether the parental mice were exposed to PM2.5 or not, the offspring mice exposure to PM2.5 appeared the elevation of blood pressure, insulin resistance, impairment of glucose tolerance, and dyslipidemia when compared to the offspring mice exposure to FA. More importantly, no matter what the offspring mice were exposed to, parental PM exposure overwhelmingly impacted the fasting blood insulin, homeostasis model assessment-insulin resistance, serous low-density lipoprotein cholesterol, and total cholesterol, splenic T helper cell 17 (Th17) and Treg cells, serous interleukin (IL)-17A, IL-6, and IL-10 in offspring mice. The results suggested that the parental exposure to air pollution might induce the development of MetS in offspring and might enhance the susceptibility of offspring to environmental hazards. The effects of parental PM exposure on offspring might be related to the changes of immune microenvironment.

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Association between proinsulin, insulin, proinsulin/insulin ratio, and insulin resistance status with the metabolic syndrome

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302007000700016 ◽

2007 ◽

Vol 51 (7) ◽

pp. 1128-1133 ◽

Cited By ~ 9

Author(s):

Ivana Pivatto ◽

Patricia Bustos ◽

Hugo Amigo ◽

Ana Maria Acosta ◽

Antonio Arteaga

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Risk Factor ◽

Resistance Index ◽

Cross Sectional Study ◽

Blood Levels ◽

Model Assessment ◽

Cross Sectional ◽

Predictive Values ◽

The Metabolic Syndrome

The Metabolic Syndrome (MS) constitutes an independent risk factor of cardiovascular disease. There is evidence that proinsulin blood levels and the proinsulin/insulin ratio are associated to the MS. The purpose of this study was to compare proinsulin and insulin, insulin resistance index, and the proinsulin/insulin ratio as predictors of MS. This is a cross-sectional study involving 440 men and 556 women with a mean age of 24 years. Diagnosis of MS was made according to the National Cholesterol Education Program Adult Treatment Panel III. Blood levels of insulin and proinsulin were measured, and the insulin resistance status was estimated using the homeostatic model assessment (HOMA-IR). The prevalence of MS was 10.1%. HOMA-IR was the best MS risk factor for both women and men (OR = 2.04; 95% CI: 1.68-2.48 and 1.09; 95% CI: 1.05-1.13, respectively). HOMA-IR presented the best positive predictive value for MS: 22% and 36% for men and women, respectively, and was the best MS indicator. The proinsulin/insulin ratio did not show significant association with MS. HOMA-IR, proinsulin, and insulin presented good negative predictive values for both genders that could be used to identify an at-risk population.

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The Metabolic Syndrome Is Associated with Reduced Central Serotonergic Responsivity in Healthy Community Volunteers

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-1654 ◽

2006 ◽

Vol 91 (2) ◽

pp. 718-721 ◽

Cited By ~ 71

Author(s):

Matthew F. Muldoon ◽

Rachel H. Mackey ◽

Mary T. Korytkowski ◽

Janine D. Flory ◽

Bruce G. Pollock ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Confidence Interval ◽

Odds Ratio ◽

Serum Prolactin ◽

Model Assessment ◽

Serotonergic Activity ◽

The Metabolic Syndrome ◽

Community Volunteers ◽

Healthy Community

Context: The pathobiology of the metabolic syndrome remains unclear. The central nervous system is likely to be involved via regulation of eating, physical activity, blood pressure, and metabolism. Objective: The objective of this study was to test the hypothesis that low central serotonergic activity is associated with the metabolic syndrome. Design, Setting, Participants: This was a cross-sectional study of 345 healthy community volunteers, aged 30–55 yr, not taking medications for hypertension, lipid disorders, or diabetes. Outcome Measures: Central serotonergic responsivity was assessed with the iv citalopram challenge test. The serum prolactin area under the curve (AUC) over 150 min was calculated, and all analyses were adjusted for age, sex, plasma citalopram concentration, and baseline prolactin. The metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Insulin resistance was estimated by homeostasis model assessment. Results: Compared with other individuals, persons meeting either NCEP or IDF criteria for the metabolic syndrome had lower mean prolactin responses (P < 0.05 for both). Using logistic regression, a decrease in prolactin AUC of 1 sd (−13.6 ng/ml·h) more than doubled the odds of having the metabolic syndrome (NCEP criteria: odds ratio, 2.38; 95% confidence interval, 1.14–4.97; P = 0.02; IDF criteria: odds ratio, 2.80; 95% confidence interval, 1.48–5.30; P = 0.002). Finally, the prolactin AUC was negatively associated with insulin resistance (β = −0.03, P = 0.02). Conclusions: Corroborating previous evidence, the metabolic syndrome was associated with diminished brain serotonergic activity as reflected in a comparative blunting of the prolactin response to a selective serotonergic challenge. This association may have implications for the etiology, prevention, and treatment of the metabolic syndrome.

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Supplementation with a Carob (Ceratonia siliqua L.) Fruit Extract Attenuates the Cardiometabolic Alterations Associated with Metabolic Syndrome in Mice

Antioxidants ◽

10.3390/antiox9040339 ◽

2020 ◽

Vol 9 (4) ◽

pp. 339

Author(s):

María de la Fuente-Fernández ◽

Daniel González-Hedström ◽

Sara Amor ◽

Antonio Tejera-Muñoz ◽

Nuria Fernández ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Ischemia Reperfusion ◽

Cardiac Contractility ◽

Density Lipoprotein ◽

Standard Diet ◽

Mrna Levels ◽

Model Assessment ◽

Fruit Extract ◽

Beneficial Effects

The incidence of metabolic syndrome (MetS) is increasing worldwide which makes necessary the finding of new strategies to treat and/or prevent it. The aim of this study was to analyze the possible beneficial effects of a carob fruit extract (CSAT+®) on the cardiometabolic alterations associated with MetS in mice. 16-week-old C57BL/6J male mice were fed for 26 weeks either with a standard diet (chow) or with a diet rich in fats and sugars (HFHS), supplemented or not with 4.8% of CSAT+®. CSAT+® supplementation reduced blood glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and circulating levels of total cholesterol, low-density lipoprotein (LDL) cholesterol (LDL-c), insulin, and interleukin-6 (IL-6). In adipose tissue and skeletal muscle, CSAT+® prevented MetS-induced insulin resistance, reduced macrophage infiltration and the expression of pro-inflammatory markers, and up-regulated the mRNA levels of antioxidant markers. Supplementation with CSAT+® prevented MetS-induced hypertension and decreased the vascular response of aortic rings to angiotensin II (AngII). Moreover, treatment with CSAT+® attenuated endothelial dysfunction and increased vascular sensitivity to insulin. In the heart, CSAT+® supplementation reduced cardiomyocyte apoptosis and prevented ischemia-reperfusion-induced decrease in cardiac contractility. The beneficial effects at the cardiovascular level were associated with a lower expression of pro-inflammatory and pro-oxidant markers in aortic and cardiac tissues.

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