ArticleArteriosclerosis, thrombosis, and vascular biology2016
Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study.
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Circulating retinol binding protein 4 levels in coronary artery disease: a systematic review and meta-analysis.Lipids in health and disease · 2021Pooled it
- Comprehensive Evaluation of Predictive Significance of FABP4 for Long-term Clinical Outcomes After Ischemic Stroke.Translational stroke research · 2026Trial
- Randomized controlled trial of landiolol, a short-acting beta-1 adrenergic receptor blocker, illustrating changes in high-molecular weight adiponectin levels after elective percutaneous coronary intervention.Heart and vessels · 2020Trial
- Adipose tissue as a humoral-neuronal hub in metabolic regulation.Nature reviews. Endocrinology · 2026Review
- Retinol-binding Protein 4 as a Predictor of Cardiovascular Events after Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction.Journal of atherosclerosis and thrombosis · 2026Article
- Circulating organokines in coronary artery disease and metabolic syndrome: FABP4, adiponectin, irisin, FSTL1.Biomolecules & biomedicine · 2025Article
- The Effects of FABP4 on Cardiovascular Disease in the Aging Population.Current atherosclerosis reports · 2024Review
- Inter-organ crosstalk during development and progression of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2024Review
- Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2023Article
- Proteomics, dietary intake, and changes in cardiometabolic health within a behavioral weight-loss intervention: A pilot study.Obesity (Silver Spring, Md.) · 2022Article
- Retinol and Retinol Binding Protein 4 Levels and Cardiometabolic Disease Risk.Circulation research · 2022Article
- Interplay of retinol binding protein 4 with obesity and associated chronic alterations (Review).Molecular medicine reports · 2022Review
- Interplay between Fatty Acid Binding Protein 4, Fetuin-A, Retinol Binding Protein 4 and Thyroid Function in Metabolic Dysregulation.Metabolites · 2022Review
- High Serum FABP4 Levels are Negatively Associated with the Reversion from Prediabetes to Normal Glucose Tolerance: A 2-Year Retrospective Cohort Community Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Cushing's syndrome is associated with altered adipokine profile.Frontiers in endocrinology · 2022Article
- Sexual Dimorphism in the Association of Serum Retinol-Binding Protein-4 With Long-Term Dynamic Metabolic Profiles in Non-Diabetes.Frontiers in endocrinology · 2022Article
- The Effects of RBP4 and Vitamin D on the Proliferation and Migration of Vascular Smooth Muscle Cells via the JAK2/STAT3 Signaling Pathway.Oxidative medicine and cellular longevity · 2022Article
- Essential Fatty Acids as Biomedicines in Cardiac Health.Biomedicines · 2021Review
- A-FABP in Metabolic Diseases and the Therapeutic Implications: An Update.International journal of molecular sciences · 2021Review
- Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study.Scientific reports · 2021Article
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Authors and funding
8 authors.
Gang LiuFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
Ming DingFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
Stephanie E ChiuveFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
Eric B RimmFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
Paul W FranksFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
James B MeigsFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
Frank B HuFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.).
Qi SunFrom the Department of Nutrition (G.L., M.D., S.E.C., E.B.R., P.W.F., F.B.H., Q.S.) and Department of Epidemiology (E.B.R., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Preventive Medicine (S.E.C.) and Channing Division of Network Medicine (E.B.R., F.B.H., Q.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden (P.W.F.); Skåne University Hospital Malmö, Sweden (P.W.F.); Department of Public Health and Clinical Medicine, Faculty of Medicine, Umeå University, Sweden (P.W.F.); Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.B.M.); and Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (J.B.M.). qisun@hsph.harvard.edu.
Funding
Cancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0MDietary Etiology of Heart DiseaseR01HL035464 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ERIC B RIMM, Qi Sun · 1986 to 2026
$13.6MCancer Epidemiology Cohort in Male Health ProfessionalsUM1CA167552 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2012 to 2016
$11.5MBIOCHEMICAL AND GENETIC MARKERS OF TYPE 2 DIABETES RISKR01DK058845 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI HU, FRANK B · 2001 to 2013
$7.8MEnvironmental Obesogens and Weight Change in the POUNDS LOST TrialR01ES022981 · NIEHS · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI SUN, QI · 2014 to 2024
$4.7MRare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6MPollutant-related diabetes in the Nurses' Health Study IIR01ES021372 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI GRANDJEAN, PHILIPPE ADAM, SUN, QI · 2013 to 2017
$2.9MEpidemiology of Precursors to Type 2 DiabetesK24DK080140 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2007 to 2016
$1.9MNovel Adipokines and Coronary Heart Disease in U.S. Men and Women with DiabetesR00HL098459 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SUN, QI · 2012 to 2014
$729kNCI NIH HHS U01 CA167552NCI NIH HHS UM1 CA167552NHLBI NIH HHS R00 HL098459NHLBI NIH HHS R01 HL035464NIDDK NIH HHS K24 DK080140NIDDK NIH HHS R01 DK058845NIDDK NIH HHS U01 DK078616NIEHS NIH HHS R01 ES021372NIEHS NIH HHS R01 ES022981
Abstract
objectiveTo examine select adipokines, including fatty acid-binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus. APPROACH AND
resultsPlasma levels of fatty acid-binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993-2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid-binding protein 4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22-2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the hazard ratio (95% confidence interval) was 2.07 (1.42-3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50-1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance.
conclusionsThese data suggest that higher levels of fatty acid-binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus.
Indexed as
AdiponectinAdultAgedBiomarkersCardiovascular DiseasesCause of DeathChi-Square DistributionDiabetes Mellitus, Type 2Fatty Acid-Binding ProteinsGenetic Predisposition to DiseaseHumansLinear ModelsMaleMendelian Randomization AnalysisMiddle AgedMolecular WeightAdiponectinADIPOQ protein, humanBiomarkersFABP4 protein, humanFatty Acid-Binding ProteinsRBP4 protein, humanRetinol-Binding Proteins, Plasmaadipokinesadiponectincardiovascular diseasefatty acid–binding proteinsheart failure
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