AS132 - A prospective study of genetic and biochemical predictors of type 2 diabetes mellitus

Investigator Names and Contact Information

Simin Liu (simin.liu@uci.edu)

Introduction/Intent

The major aim of the current proposal is to investigate genetic and biochemical markers of inflammation and endothelial dysfunction as determinants of type 2 diabetes mellitus (DM) among a large and ethnically diverse cohort of postmenopausal women with archived blood specimens. This proposal focuses on women in the observational study (OS) component of the Women’s Health Initiative (WHI) in which a total of 93,726 women will be followed for an average of 9 years. WHI is a National Institutes of Health (NIH)-sponsored study that focuses on the causes and treatments of health problems in postmenopausal women. WHI includes both a clinical trial (CT) and an observational study (OS) and will follow almost 162,000 women ages 50 to 79 for 15 years, making it the largest study in women ever undertaken in the United States. The large prospective database of diverse ethnic populations provides a unique opportunity to evaluate these novel and promising biomarkers and variations in related candidate genes as predictors of Type 2 DM, especially among minority groups. This proposal seeks funds only for the costs of managing and assaying these novel markers of endothelial dysfunction and inflammation in blood samples already collected at baseline and for the data analyses outlined below. Because the large costs associated with cohort assembly, follow-up, blood collection, storage, and endpoint validation are already funded as part of the WHI (N01-WH-2-2110), the current proposal also represents an exceptionally cost-effective means to study the etiology of type 2 DM. The specific aims of the present proposal are the followings:

Aims

  1. To examine inflammatory and endothelial biomarkers as risk factors of type 2 DM, we hypothesize that:

  2. To evaluate promising candidate genes that are related to insulin resistance, particularly, endothelial dysfunction and inflammation as predictors of type 2 DM; specifically, we propose to:

Each of the proposed biomarkers can be readily measured in the WHI-OS archived specimens. We will first assess the independent and joint contributions of these novel inflammatory cytokines, acute-phase reactant, and activated endothelial markers in the development of Type 2 DM in a large and ethnically diverse cohort of postmenopausal women. Second, we will focus on specific candidate genes that are both physiological relevant and that some contributions of these genes to predicting type 2 DM risk have been suspected but not yet confirmed. These will include genes that directly affect endothelial dysfunction (including TNF-a, NOS3, PPARg ), obesity and insulin resistance (TNF-a, PPARg, UCP2, CAPN10, and aP2). We also propose to conduct a comprehensive and yet focused evaluation of polymorphisms within several promising candidate genes of type 2 DM susceptibility. Furthermore, most genetic studies of type 2 DM have come from Caucasian or American-Indian populations and little data are available from other ethnic populations. Because previous studies have demonstrated that the susceptibility genes may vary significantly across different populations, comparison of data from different ethnic groups will certainly improve our understanding of the genetic contributions in the etiology of type 2 DM. Findings from this series of comprehensive and focused analyses among ethnically diverse groups of women could shed new light on the etiology of Type 2 DM and may suggest new intervention strategies to reduce the incidence of type 2 DM, especially in minority populations.

Results/Findings

Some of the publications related to this ancillary study are:

Ms369 - Liu S, Tinker L, Song Y, Rifai N, Bonds DE, Cook NR, Heiss G, Howard BV, Hotamisligil GS, Hu FB, Kuller LH, Manson JE. A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. Arch Intern Med. 2007 Aug 13-27;167(15):1676-85.

Ms376 - Song Y, Manson JE, Tinker L, Rifai N, Cook NR, Hu FB, Hotamisligil GS, Ridker PM, Rodriguez BL, Margolis KL, Oberman A, Liu S. Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women. Diabetes. 2007 Jul;56(7):1898-904. Epub 2007 Mar 27.

Ms486 - Song Y, Manson JE, Tinker L, Howard BV, Kuller LH, Nathan L, Rifai N, Liu S. Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: The Women's Health Initiative Observational Study. Diabetes Care. 2007 Jul;30(7):1747-52. Epub 2007 Apr 27.

Ms550 - Song Y, You NC, Hsu YH, Sul J, Wang L, Tinker L, Eaton CB, Liu S. Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal women. Hum Mol Genet. 2007 Dec 1;16(23):2960-71. Epub 2007 Sep 12.

Ms554 - Hsu Y, Niu T, Song Y, Tinker L, Kuller LH, Liu S. Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study. Diabetes. 2008 Apr;57(4):1101-7. Epub 2008 Jan 25.

Ms555 - Chan KH, Niu T, Ma Y, You NC, Song Y, Sobel EM, Hsu YH, Balasubramanian R, Qiao Y, Tinker L, Liu S. Common genetic variants in Peroxisome Proliferator-Activated Receptor-γ (PPARG) and Type 2 Diabetes risk among Women's Health Initiative postmenopausal women. J Clin Endocrinol Metab. 2013 Mar;98(3):E600-4. doi: 10.1210/jc.2012-3644. Epub 2013 Feb 5

Ms572 - Chan KH, Song Y, Hsu YH, You NC, F Tinker L, Liu S. Common genetic variants in Fatty Acid-Binding Protein-4 (FABP4) and clinical diabetes risk in the Women's Health Initiative Observational Study. Obesity (Silver Spring). 2010 Jan 28. [Epub ahead of print]

Ms582 - Chao C, Song Y, Cook N, Tseng CH, Manson JE, Eaton C, Margolis KL, Rodriguez B, Phillips LS, Tinker LF, Liu S. The lack of utility of circulating biomarkers of inflammation and endothelial dysfunction for Type 2 diabetes risk prediction among postmenopausal women: The Women's Health Initiative Observational Study. Arch Intern Med. 2010 Sep 27;170(17):1557-65

Ms594 - Ma Y, Hébert JR, Li W, Bertone-Johnson ER, Olendzki B, Pagoto SL, Tinker L, Rosal MC, Ockene IS, Ockene JK, Griffith JA, Liu S. Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study. Nutrition. 2008 Oct;24(10):941-9. Epub 2008 Jun 18.

Ms660 - Lee CC, You NC, Song Y, Hsu YH, Manson J, Nathan L, Tinker L, Liu S. Relation of genetic variation in the gene coding for c-reactive protein with its plasma protein concentrations: Findings from the Women's Health Initiative Observational Cohort. Clin Chem. 2009 Feb;55(2):351-60. Epub 2008 Dec 18

Ms664 - Song Y, You NC, Hsu YH, Howard BV, Langer RD, Manson JE, Nathan L, Niu T, F Tinker L, Liu S. FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women. Obesity (Silver Spring). 2008 Nov;16(11):2472-80. Epub 2008 Sep 11.

Ms688 - Chacko SA, Song Y, Nathan L, Tinker L, de Boer IH, Tylavsky F, Wallace R, Liu S. Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care. 2010 Feb;33(2):304-10. Epub 2009 Nov 10

Ms719 - Ma Y, Balasubramanian R, Pagoto SL, Schneider KL, Culver AL, Olendzki B, Tinker L, Liu S, Safford M, Sepavich DM, Rosal MC, Ockene JK, Carnethon M, Zorn M, Hébert JR. Elevated depressive symptoms, antidepressant use, and diabetes in a large multiethnic national sample of postmenopausal women. Diabetes Care. 2011 Sep 12. [Epub ahead of print]

Ms1148 - Chan KH, Brennan K, You NC, Lu X, Song Y, Hsu YH, Chaudhuri G, Nathan L, Tinker L, Liu S. Common variations in the genes encoding c-reactive protein, tumor necrosis factor, and interleukin-6, and the risk of clinical diabetes in the Women’s Health Initiative Observational Study. Clin Chem. 2010 Dec 13. [Epub ahead of print]

For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.

Data Dictionaries and Study Documentation

This section displays all study-related data dictionaries and study-related files. The investigators for this study will upload the datasets, data dictionaries, and other study-related files. Study-related files will be made available to the public one year after the completion of the ancillary study, with the exception of the datasets, which will only be available to those with a Data Distribution Agreement. Those will be available to those with permission to download and will appear as a download link next to the data dictionary

Data Dictionaries

Name
Description
No results found

Study Documents

Name
Description
NameAS132Matching Summary.pdfDescription
NameAS132Matching SummaryPart2.pdfDescription

Related Papers

Shared molecular pathways and gene networks for cardiovascular disease and type 2 diabetes mellitus in women across diverse ethnicities

Kei-Hang Katie Chan et al., 2014/11 PubMed #25371518 MSID: 1024
Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors, potential molecular mechanisms that may also be shared for these 2 disorders remain unknown.Using an integrative pathway and network analysis, we performed genome-wide association studies in 8155 blacks, 3494 Hispanic American, and 3697 Caucasian American women who participated in the national Women's Health Initiative single-nucleotide polymorphism (SNP) Health Association Resource and the G...
Keywords: Diabetes Mellitus; Gwas; Gene-Gene; Gene-Environment Interaction; Phenotypes; Integrated Approach; Gene-Set Enrichment Analysis
Related Studies: 132, M5

Association between endophenotypic targets of Metformin and type 2 diabetes risk using mendelian randomization approach

Approved Proposal, Chan, Kei-Hang Katie et al., 2015/8 MSID: 2742
Keywords: Genes; Metformin; Biochemical Markers; T2d; Mendelian Randomization
Related Studies: 129, 132, 238

Mendelian randomization analysis of type 2 diabetes and sex hormone-binding globulin and leukocyte telomere length in women

Approved Proposal, Gong, Jungho et al., 2019/6 MSID: 3926
Keywords: Sex-Hormone Binding Globulin; Leukocyte Telomere Length; Inflammatory And Endothelial Markers; Diabetes; Obesity
Related Studies: 132, 238, 254

Biomarkers of inflammation, pregnancy loss, and cardiovascular disease risk

Approved Proposal, Wright, Catherine et al., 2021/1 MSID: 4354
Keywords: Inflammation; Biomarkers; Reproductive History; Miscarriage; Cardiovascular Disease

The portfolio diet and incident type 2 diabetes: Findings from the Women's Health Initiative prospective cohort study

Andrea Glenn et al., 2022/9 PubMed #36162007 MSID: 3669
Objective: A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes. Research design and methods: This analysis included 145,299 postmenopausal women free of diabetes at baseline in the Women's Health Initiative (WHI) Clinical Trials and Observational Study from 1993 to 2021. Adherence to the diet was assessed with a score bas...
Keywords: Portfolio Diet; Cardiovascular Disease; Prospective Cohort; Nutritional Epidemiology; Dietary Patterns
Related Studies: 132, 238, 254

Assessing the effects of multiple continuous mediators on a dichotomous outcome

Approved Manuscript, Shih, Stephanie et al., 2017/5 MSID: 3357
Related Studies: 132, 238, 254

Identifying the effects of multiple dichotomous mediators on a dichotomous outcome

Approved Manuscript, Shih, Stephanie et al., 2017/5 MSID: 3358
Related Studies: 132, 238, 254

Insulin level and risk of non-Hodgkin lymphoma among postmenopausal women in The Women’s Health Initiative

Approved Proposal, Peila, Rita et al., 2016/11 MSID: 3202
Keywords: Insulin; Type 2 Diabetes; Inflammation; C-Reactive Protein; Non-Hodgkin Lymphoma

Mediation analysis with multiple mediators

Approved Proposal, Shih, Stephanie et al., 2016/9 MSID: 3170
Keywords: Type 2 Diabetes; Mediation Analysis; Sex-Hormone Binding Globulin; Sex-Steroids; Telomere Length; Inflammatory Markers; Endothelial Markers And Glucose And Insulin; Low Birthweight; Insulin Sensitivity
Related Studies: 132, 238, 254

Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study

Yi-Hsiang Hsu et al., 2008/1 PubMed #18223008 MSID: 554
Mitochondrial uncoupling proteins (UCPs) are involved in body weight regulation and glucose homeostasis. Genetic variants in the UCP2-UCP3 gene cluster, located on chromosome 11q13, may play a significant role in the development of type 2 diabetes.We conducted a comprehensive assessment of common single nucleotide polymorphisms (SNPs) at the 70-kb UCP2-UCP3 gene cluster in relation to type 2 diabetes risk in a prospective, case-control study nested in the Women's Health Initiative Observational ...
Keywords: Ucp2; Type 2 Diabetes; The Women’S Health Initiative –Observational Study (Whi-Os); Haplotype
Related Studies: 132

Common genetic variants in Peroxisome Proliferator-Activated Receptor-? (PPARG) and Type 2 Diabetes risk among Women's Health Initiative postmenopausal women

Kei-Hang Katie Chan et al., 2013/2 PubMed #23386649 MSID: 555
Peroxisome proliferator-activated receptor-? (PPARG) plays a pivotal role in adipogenesis and glucose homeostasis.We investigated whether PPARG gene variants were associated with type 2 diabetes (T2D) risk in the multiethnic Women's Health Initiative (WHI).We assessed PPARG single-nucleotide polymorphisms (SNPs) in a case-control study nested in the prospective WHI observational study (WHI-OS) (1543 T2D cases and 2170 matched controls). After identifying 24 tagSNPs, we used multivariable logisti...
Keywords: Ppar Gamma; Type 2 Diabetes Mellitus; Genotype; Haplotype; Association Studies
Related Studies: 132

Sex hormone-binding globulin levels and telomere length in postmenopausal diabetic women

Approved Proposal, Gately, Kaitlin et al., 2018/4 MSID: 3550
Keywords: Sex-Hormones; Sex-Hormone-Binding Globulin; Leukocyte Telomeres; Diabetes; Postmenopausal Women
Related Studies: 132, 238, 254

Common genetic variants in Fatty Acid-Binding Protein-4 (FABP4) and clinical diabetes risk in the Women's Health Initiative Observational Study

Kei-Hang Katie Chan et al., 2010/1 PubMed #20111020 MSID: 572
Adipocypte fatty acid-binding protein-4 (FABP4/adipocyte P2) may play a central role in energy metabolism and inflammation. In animal models, defects of the aP2 gene (aP2(-/-)) partially protected against the development of obesity-related insulin resistance, dyslipidemia, and atherosclerosis. However, it is unclear whether common genetic variation in FABP4 gene contributes to risk of type 2 diabetes (T2D) or diabetes-related metabolic traits in humans. We comprehensively assess the genetic asso...
Keywords: Fabp4; Ap2; Type 2 Diabetes; The Women’S Health Initiative –Observational Study (Whi-Os); Haplotype; Polymorphism; And Variant
Related Studies: 132

Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: The Women's Health Initiative Observational Study

Yiqing Song et al., 2007/7 PubMed #17468352 MSID: 486
The homeostasis model assessment (HOMA), based on plasma levels of fasting glucose and insulin, has been widely validated and applied for quantifying insulin resistance and beta-cell function. However, prospective data regarding its relation to diabetes risk in ethnically diverse populations are limited.Among 82,069 women who were aged 50-79 years, free of cardiovascular disease or diabetes, and participating in the Women's Health Initiative Observational Study, we conducted a nested case-contro...
Keywords: Type 2 Diabetes Mellitus (Type 2 Dm); Fasting Insulin Levels; Glucose Levels; Insulin Resistance; Insulin Secretion; The Homeostasis Model Assessment (Homa)
Related Studies: 132

FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women

Yiqing Song et al., 2008/9 PubMed #18787525 MSID: 664
The FTO gene was recently identified as a susceptibility locus for both obesity and type 2 diabetes by whole-genome association analyses of several European populations. We tested for an association between FTO risk alleles and obesity and diabetes in a well-characterized multiethnic cohort of postmenopausal women in the United States. We genotyped two most significantly associated single-nucleotide polymorphisms (SNPs) (rs9939609 and rs8050136) in intron 1 of FTO gene in a nested case-control s...
Keywords: Fto Gene; Variant; Snp; Body Mass Index; Obesity; Adiposity; Diabetes Mellitus; Ethnicity
Related Studies: 132

Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women

Sara Chacko et al., 2009/11 PubMed #19903755 MSID: 688
Although magnesium may favorably affect metabolic outcomes, few studies have investigated the role of magnesium intake in systemic inflammation and endothelial dysfunction in humans.Among 3,713 postmenopausal women aged 50-79 years in the Women's Health Initiative Observational Study and free of cardiovascular disease, cancer, and diabetes at baseline, we measured plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), turnor necrosis factor-alpha receptor 2 ...
Keywords: Vitamin D; Calcium; Magnesium; High Sensitivity C-Reactive Protein; Interleukin-6; Tumor Necrosis Factor Alpha; Inflammatory Cytokines
Related Studies: 132

The utility of circulating biomarkers of inflammation and endothelial dysfunction for risk prediction and stratification of clinical diabetes in postmenopausal women – The Women’s Health Initiative Observational Study

Chun Chao et al., 2010/9 PubMed #20876407 MSID: 582
Recent studies have linked plasma markers of inflammation and endothelial dysfunction to type 2 diabetes mellitus (DM) development. However, the utility of these novel biomarkers for type 2 DM risk prediction remains uncertain.The Women's Health Initiative Observational Study (WHIOS), a prospective cohort, and a nested case-control study within the WHIOS of 1584 incident type 2 DM cases and 2198 matched controls were used to evaluate the utility of plasma markers of inflammation and endothelial ...
Keywords: Type 2 Diabetes Mellitus; C-Reactive Protein; Interleukin-6; Tumor Necrosis Factor-A; Inflammation; E-Selectin; Intercellular Adhension Molecule-1; Vascular Cell Adhesion Molecule-1; Endothelial Adhesion Molecules; Risk Prediction; Risk Score
Related Studies: 132

Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study

Yunsheng Ma et al., 2008/6 PubMed #18562168 MSID: 594
Systemic inflammation may play an important role in the development of atherosclerosis, type 2 diabetes, and some cancers. Few studies have comprehensively assessed the direct relations between dietary fiber and inflammatory cytokines, especially in minority populations. Using baseline data from 1958 postmenopausal women enrolled in the Women's Health Initiative Observational Study, we examined cross-sectional associations between dietary fiber intake and markers of systemic inflammation (includ...
Keywords: Dietary Fiber; C-Reactive Protein; Epidemiology; Cardiovascular Disease; Nutrition
Related Studies: 132

Common variations in the genes encoding c-reactive protein, tumor necrosis factor, and interleukin-6, and the risk of clinical diabetes in the Women’s Health Initiative Observational Study

Kei-Hang Katie Chan et al., 2010/12 PubMed #21149504 MSID: 1148
Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes.To examine the roles of genetic variation in the genes encoding CRP, TNF- a, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diab...
Keywords: C-Reactive Protein; Crp; Diabetes; Interleukin-6; Il-6; Tumor Necrosis Factor Alpha; Tnf-A
Related Studies: 132

Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and Hispanic American women

Kei-Hang Katie Chan et al., 2015/3 PubMed #25733456 MSID: 1050
BACKGROUND: Prospective studies consistently link low magnesium intake to higher type 2 diabetes (T2D) risk. OBJECTIVE: We examined the association of common genetic variants [single nucleotide polymorphisms (SNPs)] in genes related to magnesium homeostasis with T2D risk and potential interactions with magnesium intake. METHODS: Using the Women's Health Initiative-SNP Health Association Resource (WHI-SHARe) study, we identified 17 magnesium-related ion channel genes (583 SNPs) and examined their...
Keywords: Transient Receptor Potential Membrane Melastatin 6 And 7 (Trpm6 And Trpm7); Polymorphism; Magnesium; Systemic Inflammation; High Sensitivity C-Reactive Protein (Hs-Crp); Interleukin-6 (Il-6); Tumor Necrosis Factor Alpha (Tnf-A); Type 2 Diabetes
Related Studies: 132, M5

Common genetic variation in the endothelial nitric oxide synthase (NOS3) gene and type 2 diabetes in an ethnically diverse cohort of women

Approved Proposal, Liu, Simin et al., 2006/8 MSID: 573
Keywords: Nos3; Endothelium; Nitric Oxide (No); Type 2 Diabetes; The Women’S Health Initiative –Observational Study (Whi-Os); Polymorphism; Haplotype
Related Studies: 132

Elevated depressive symptoms, antidepressant use, and diabetes in a large multiethnic national sample of postmenopausal women

Yunsheng Ma et al., 2011/9 PubMed #21911776 MSID: 719
To examine elevated depressive symptoms and antidepressant use in relation to diabetes incidence in the Women's Health Initiative.A total of 161,808 postmenopausal women were followed for over an average of 7.6 years. Hazard ratios (HRs) estimating the effects of elevated depressive symptoms and antidepressant use on newly diagnosed incident diabetes were obtained using Cox proportional hazards models adjusted for known diabetes risk factors.Multivariable-adjusted HRs indicated an increased risk...
Keywords: Depression; Type 2 Diabetes; Epidemiology
Related Studies: 132

Relation of genetic variation in the gene coding for c-reactive protein with its plasma protein levels: Findings from the Women’s Health Initiative observational cohort

Cathy Lee et al., 2008/12 PubMed #19095725 MSID: 660
Although common genetic variants of the CRP gene (C-reactive protein, pentraxin related) have been associated with plasma concentrations of high-sensitivity CRP (hsCRP) in several cohorts of European Americans, relatively few studies have comprehensively assessed this association in well-characterized multiethnic populations.In a case-control study of diabetes nested in the Women's Health Initiative Observational Cohort, we comprehensively evaluated the association of genetic variation in CRP wi...
Keywords: C-Reactive Protein; Interleukin-6; Tumor Necrosis Factor Alpha; Inflammatory Cytokines; Diabetes Mellitus; Polymorphism; Haplotype
Related Studies: 132

Dietary antioxidants, inflammation and diabetes mellitus in a multi-ethnic cohort of postmenopausal women

Approved Proposal, Rodriguez, Rachelle et al., 2007/11 MSID: 668
Keywords: Dietary Antioxidants; Vitamin E; Vitamin C; Beta-Carotene; Alpha-Carotene; Lycopene; Carotenes; Carotenoids; Zinc; Copper; Selenium; Magnesium; Coffee; Inflammation; Tumor Necrosis Factor- A; C-Reactive Protein; Interleukin-6; Type 2 Diabetes
Related Studies: 132

A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women

Simin Liu et al., 2007/8 PubMed #17698692 MSID: 369
Inflammatory cytokines, including tumor necrosis factor alpha, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations.Among 82,069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's He...
Keywords: Type 2 Diabetes Mellitus; Interleukin-6; Tumor Necrosis Factor-A; C-Reactive Protein; Inflammation; Insulin Resistance
Related Studies: 132

Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women

Yiqing Song et al., 2007/7 PubMed #17389327 MSID: 376
Elevated circulating levels of soluble adhesion molecules as markers of endothelial dysfunction have been related to insulin resistance and its associated metabolic abnormalities. However, their associations with type 2 diabetes remain inconclusive. We conducted a prospective nested case-control study to examine the associations between plasma levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) and diabetes risk among 82,069 initially ...
Keywords: Type 2 Diabetes Mellitus; Endothelial Activation; E-Selectin; Intercellular Adhesion Molecule-1; Vascular Adhesion Molecule-1; Insulin Resistance
Related Studies: 132

Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women

Yan Song et al., 2015/1 PubMed #25567102 MSID: 2072
AIMS/HYPOTHESIS: The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk. METHODS: We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were...
Keywords: Birth Weight; Type 2 Diabetes; Insulin Resistance; Telomere; Inflammation; Endothelial Dysfunction; Sex Steroid
Related Studies: 132, 238, 254

Understanding the relation between socioeconomic position and inflammation in post-menopausal women: education, income and occupational prestige

Jolene Masters Pedersen et al., 2017/12 PubMed #29186460 MSID: 1738
BACKGROUND: The role of occupational prestige, a direct measure of the perceived status of job and job holder, in inflammation is unknown. To contribute to understanding the pathways by which socioeconomic position (SEP) is associated with inflammation, we aimed to estimate the direct effects of education, income and occupational prestige on C-reactive protein (CRP) and to describe the relationship between these markers and CRP. METHODS: The study was based on 2026 post-menopausal women enrolled...
Keywords: Occupation; Socioeconomic Position; Low Grade Inflammation
Related Studies: 126, 132

Dietary manganese, plasma markers of inflammation, and the development of Type 2 Diabetes in postmenopausal women: Findings from the Women's Health Initiative

Jungho Gong et al., 2020/4 PubMed #32295807 MSID: 3998
Objective: To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation. Research design and methods: We included 84,285 postmenopausal women without a history of diabetes from the national Women's Health Initiative Observational Study (WHI-OS). Replication analysis was then conducted among 62,338 women who participated in the WHI-Clinical Trial (WHI-CT). Addit...
Keywords: Dietary Manganese; Inflammatory And Endothelial Markers; Diabetes; Obesity
Related Studies: 132

Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal women

Yiqing Song et al., 2007/12 PubMed #17855447 MSID: 550
Calpain-10 (CAPN10) protein may play a role in glucose metabolisms, pancreatic beta-cell insulin secretion and thermogenesis. Emerging evidence has implicated a role of CAPN10 genetic variants in the risk of type 2 diabetes mellitus (T2DM). Previous association studies, however, have focussed only on several variants initially reported and provided inconsistent results. We conducted a large nested case-control study to comprehensively investigate the associations between common variations in CAP...
Keywords: Calpain-10 (Capn10); Haplotype; Type 2 Diabetes; The Women’S Health Initiative Observational Study (Whi-Os)
Related Studies: 132

Genetic interleukin-6 receptor blockade, chronic disease risk and longevity

Approved Manuscript, Haring, Bernhard et al., 2024/12 MSID: 5099
Keywords: Inflammation; Ageing; Longevity; Chronic Disease Risk; Chd; Dementia; Chf
Related Studies: 126, 132

Inflammation, body weight change, CVD and mortality risk. Results from the Women’s Health Initiative

Approved Proposal, Haring, Bernhard et al., 2025/1 MSID: 5257
Keywords: Inflammation; Weight Change; Il-6; Il-6 Inhibition; Hscrp
Related Studies: 126, 132

Manganese intake and the risk of cardiovascular disease in postmenopausal women: findings from the Women’s Health Initiative

Approved Proposal, Lo, Kenneth et al., 2020/3 MSID: 4003
Keywords: Dietary Manganese; Cardiovascular Disease; Hypertension; Inflammatory And Endothelial Markers; Diabetes; Obesity
Related Studies: 132

Association of the portfolio diet with risk of cardiovascular disease in the Women’s Health Initiative: A prospective cohort study

Approved Manuscript, Glenn, Andrea et al., 2020/3 MSID: 3722
Keywords: Portfolio Diet; Cardiovascular Disease; Prospective Cohort; Nutritional Epidemiology; Dietary Patterns
Related Studies: 132, 238, 254

Evaluation of the association between circulating IL-1β and related cytokines and incident atrial fibrillation in a cohort of postmenopausal women

Marco Perez et al., 2023/1 PubMed #36646198 MSID: 2432
Background: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1β, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF. Methods: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, educatio...
Keywords: Atrial Fibrillation; Myocytokines; Il-6; Crp; Biomarkers; Inflammation