Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2020

01-12-2020 | Echocardiography | Original investigation

Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study

Authors: Mei-Zhen Wu, Chi-Ho Lee, Yan Chen, Shuk-Yin Yu, Yu-Juan Yu, Qing-Wen Ren, Ho-Yi Carol Fong, Pui-Fai Wong, Hung-Fat Tse, Siu-Ling Karen Lam, Kai-Hang Yiu

Published in: Cardiovascular Diabetology | Issue 1/2020

Login to get access

Abstract

Background

The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM.

Methods

Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively.

Results

The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e′ (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (β = 0.89, P < 0.01) and worsening of average E/e′ (β = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16–6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease.

Conclusion

Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.
Appendix
Available only for authorised users
Literature
1.
Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972;30(6):595–602. PubMedCrossRef
2.
Eguchi K, Boden-Albala B, Jin Z, Rundek T, Sacco RL, Homma S, et al. Association between diabetes mellitus and left ventricular hypertrophy in a multiethnic population. Am J Cardiol. 2008;101(12):1787–91. PubMedPubMedCentralCrossRef
3.
Jørgensen PG, Jensen MT, Mogelvang R, Fritz-Hansen T, Galatius S, Biering-Sørensen T, et al. Impact of type 2 diabetes and duration of type 2 diabetes on cardiac structure and function. Int J Cardiol. 2016;221:114–21. PubMedCrossRef
4.
Ernande L, Audureau E, Jellis CL, Bergerot C, Henegar C, Sawaki D, et al. Clinical Implications of Echocardiographic Phenotypes of Patients With Diabetes Mellitus. J Am Coll Cardiol. 2017;70(14):1704–16. PubMedCrossRef
5.
Zhang HW, Jin JL, Cao YX, Liu HH, Zhang Y, Guo YL, et al. Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study. Cardiovasc Diabetol. 2020;19(1):15. PubMedPubMedCentralCrossRef
6.
Nguyen HC, Qadura M, Singh KK. Role of the fatty acid binding proteins in cardiovascular diseases: a systematic review. J Clin Med. 2020;9(11):3390. CrossRefPubMedCentral
7.
Xu A, Wang Y, Xu JY, Stejskal D, Tam S, Zhang J, et al. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem. 2006;52(3):405–13. PubMedCrossRef
8.
Xu A, Tso AW, Cheung BM, Wang Y, Wat NM, Fong CH, et al. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation. 2007;115(12):1537–43. PubMedCrossRef
9.
Lorenzo-Almorós A, Hang T, Peiró C, Soriano-Guillén L, Egido J, Tuñón J, et al. Predictive and diagnostic biomarkers for gestational diabetes and its associated metabolic and cardiovascular diseases. Cardiovasc Diabetol. 2019;18(1):140. PubMedPubMedCentralCrossRef
10.
Tso AW, Xu A, Sham PC, Wat NM, Wang Y, Fong CH, et al. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort. Diabetes Care. 2007;30(10):2667–72. PubMedCrossRef
11.
Furuhashi M, Yuda S, Muranaka A, Kawamukai M, Matsumoto M, Tanaka M, et al. Circulating fatty acid-binding protein 4 concentration predicts the progression of carotid atherosclerosis in a general population without medication. Circ J. 2018;82(4):1121–9. PubMedCrossRef
12.
Chow WS, Tso AW, Xu A, Yuen MM, Fong CH, Lam TH, et al. Elevated circulating adipocyte-fatty acid binding protein levels predict incident cardiovascular events in a community-based cohort: a 12-year prospective study. J Am Heart Assoc. 2013;2(1):e004176. PubMedPubMedCentralCrossRef
13.
Wong YK, Cheung CYY, Tang CS, Au KW, Hai JSH, Lee CH, et al. Age-biomarkers-clinical risk factors for prediction of cardiovascular events in patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2018;38(10):2519–27. PubMedCrossRef
14.
Tseng PW, Hou JS, Wu DA, Hsu BG. High serum adipocyte fatty acid binding protein concentration linked with increased aortic arterial stiffness in patients with type 2 diabetes. Clin Chim Acta. 2019;495:35–9. PubMedCrossRef
15.
Lee CH, Cheung CYY, Woo YC, Lui DTW, Yuen MMA, Fong CHY, et al. Circulating adipocyte fatty acid-binding protein concentrations predict multiple mortality outcomes among men and women with diabetes. Clin Chem. 2018;64(10):1496–504. PubMedCrossRef
16.
Liu G, Ding M, Chiuve SE, Rimm EB, Franks PW, Meigs JB, et al. 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. Arterioscler Thromb Vasc Biol. 2016;36(11):2259–67. PubMedPubMedCentralCrossRef
17.
Liu M, Zhou M, Bao Y, Xu Z, Li H, Zhang H, et al. Circulating adipocyte fatty acid-binding protein levels are independently associated with heart failure. Clin Sci (Lond). 2013;124(2):115–22. CrossRef
18.
Djoussé L, Bartz TM, Ix JH, Kochar J, Kizer JR, Gottdiener JS, et al. Fatty acid-binding protein 4 and incident heart failure: the Cardiovascular Health Study. Eur J Heart Fail. 2013;15(4):394–9. PubMedCrossRef
19.
Fuseya T, Furuhashi M, Yuda S, Muranaka A, Kawamukai M, Mita T, et al. Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population. Cardiovasc Diabetol. 2014;13:126. PubMedPubMedCentralCrossRef
20.
Baessler A, Lamounier-Zepter V, Fenk S, Strack C, Lahmann C, Loew T, et al. Adipocyte fatty acid-binding protein levels are associated with left ventricular diastolic dysfunction in morbidly obese subjects. Nutr Diabetes. 2014;4:e106. PubMedPubMedCentralCrossRef
21.
Engeli S, Utz W, Haufe S, Lamounier-Zepter V, Pofahl M, Traber J, et al. Fatty acid binding protein 4 predicts left ventricular mass and longitudinal function in overweight and obese women. Heart. 2013;99(13):944–8. PubMedCrossRef
22.
von Jeinsen B, Short MI, Xanthakis V, Carneiro H, Cheng S, Mitchell GF, et al. Association of circulating adipokines with echocardiographic measures of cardiac structure and function in a community-based cohort. J Am Heart Assoc. 2018;7:13.
23.
von Jeinsen B, Ritzen L, Vietheer J, Unbehaun C, Weferling M, Liebetrau C, et al. The adipokine fatty-acid binding protein 4 and cardiac remodeling. Cardiovasc Diabetol. 2020;19(1):117. CrossRef
24.
Chen Y, Zhao CT, Zhen Z, Wong A, Tse HF, Yiu KH. Association of myocardial dysfunction with vitamin D deficiency in patients with type 2 diabetes mellitus. J Diabetes Complications. 2014;28(3):286–90. PubMedCrossRef
25.
Liu JH, Chen Y, Zhen Z, Ho LM, Tsang A, Yuen M, et al. Relationship of biomarkers of extracellular matrix with myocardial function in Type 2 diabetes mellitus. Biomark Med. 2017;11(7):569–78. PubMedCrossRef
26.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12. PubMedPubMedCentralCrossRef
27.
Ong KL, Rye KA, O’Connell R, Jenkins AJ, Brown C, Xu A, et al. Long-term fenofibrate therapy increases fibroblast growth factor 21 and retinol-binding protein 4 in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2012;97(12):4701–8. PubMedCrossRef
28.
Lee CH, Cheung CYY, Woo YC, Lui DTW, Yuen MMA, Fong CHY, et al. Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes. Diabetologia. 2019;62(1):169–77. PubMedCrossRef
29.
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16(3):233–70. PubMedCrossRef
30.
Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57(6):450–8. PubMedCrossRef
31.
Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016;17(12):1321–60. PubMedCrossRef
32.
Classification and Diagnosis of Diabetes. Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S14-s31.
33.
Balci MM, Arslan U, Firat H, Kocaoğlu I, Vural MG, Balci KG, et al. Serum levels of adipocyte fatty acid-binding protein are independently associated with left ventricular mass and myocardial performance index in obstructive sleep apnea syndrome. J Investig Med. 2012;60(7):1020–6. PubMedCrossRef
34.
Lamounier-Zepter V, Look C, Alvarez J, Christ T, Ravens U, Schunck WH, et al. Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. Circ Res. 2009;105(4):326–34. PubMedCrossRef
35.
Zhang J, Qiao C, Chang L, Guo Y, Fan Y, Villacorta L, et al. Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy. PLoS ONE. 2016;11:e0157372. PubMedPubMedCentralCrossRef
36.
Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation. 2000;102(15):1788–94. PubMedCrossRef
37.
Marwick TH, Ritchie R, Shaw JE, Kaye D. Implications of underlying mechanisms for the recognition and management of diabetic cardiomyopathy. J Am Coll Cardiol. 2018;71(3):339–51. PubMedCrossRef
38.
Zhao CT, Wang M, Siu CW, Hou YL, Wang T, Tse HF, et al. Myocardial dysfunction in patients with type 2 diabetes mellitus: role of endothelial progenitor cells and oxidative stress. Cardiovasc Diabetol. 2012;11:147. PubMedPubMedCentralCrossRef
39.
Sacre JW, Franjic B, Jellis CL, Jenkins C, Coombes JS, Marwick TH. Association of cardiac autonomic neuropathy with subclinical myocardial dysfunction in type 2 diabetes. JACC Cardiovasc Imaging. 2010;3(12):1207–15. PubMedCrossRef
40.
Moir S, Hanekom L, Fang ZY, Haluska B, Wong C, Burgess M, et al. Relationship between myocardial perfusion and dysfunction in diabetic cardiomyopathy: a study of quantitative contrast echocardiography and strain rate imaging. Heart. 2006;92(10):1414–9. PubMedPubMedCentralCrossRef
41.
De Jong KA, Czeczor JK, Sithara S, McEwen K, Lopaschuk GD, Appelbe A, et al. Obesity and type 2 diabetes have additive effects on left ventricular remodelling in normotensive patients-a cross sectional study. Cardiovasc Diabetol. 2017;16(1):21. PubMedPubMedCentralCrossRef
42.
Zoppini G, Bergamini C, Bonapace S, Rossi A, Trombetta M, Mantovani A, et al. Association between subclinical left ventricular systolic dysfunction and glycemic control in asymptomatic type 2 diabetic patients with preserved left ventricular function. J Diabetes Complications. 2017;31(6):1035–40. PubMedCrossRef
43.
Walraven I, van Hurk K, van Riet E, Kamp O, Schalkwijk CG, Stehouwer CD, et al. Low-grade inflammation and endothelial dysfunction explain the association between retinopathy and left ventricular ejection fraction in men: an 8-year follow-up of the Hoorn Study. J Diabetes Complications. 2014;28(6):819–23. PubMedCrossRef
44.
Kroon MH, van den Hurk K, Alssema M, Kamp O, Stehouwer CD, Henry RM, et al. Prospective associations of B-type natriuretic peptide with markers of left ventricular function in individuals with and without type 2 diabetes: an 8-year follow-up of the Hoorn Study. Diabetes Care. 2012;35(12):2510–4. PubMedPubMedCentralCrossRef
45.
Wu MZ, Chen Y, Zou Y, Zhen Z, Yu YJ, Liu YX, et al. Impact of obesity on longitudinal changes to cardiac structure and function in patients with Type 2 diabetes mellitus. Eur Heart J Cardiovasc Imaging. 2019;20(7):816–27. PubMedCrossRef
46.
47.
Rodríguez-Calvo R, Girona J, Rodríguez M, Samino S, Barroso E, de Gonzalo-Calvo D, et al. Fatty acid binding protein 4 (FABP4) as a potential biomarker reflecting myocardial lipid storage in type 2 diabetes. Metabolism. 2019;96:12–21. PubMedCrossRef
48.
Rijzewijk LJ, van der Meer RW, Smit JW, Diamant M, Bax JJ, Hammer S, et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008;52(22):1793–9. PubMedCrossRef
49.
Zhou M, Bao Y, Li H, Pan Y, Shu L, Xia Z, et al. Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction. Clin Sci (Lond). 2015;129(7):547–59. CrossRef
50.
Li S, Bi P, Zhao W, Lian Y, Zhu H, Xu D, et al. Prognostic utility of fatty acid-binding protein 4 in patients with type 2 diabetes and acute ischemic stroke. Neurotox Res. 2018;33(2):309–15. PubMedCrossRef
51.
Markus MR, Werner N, Schipf S, Siewert-Markus U, Bahls M, Baumeister SE, et al. Changes in Body Weight and Composition Are Associated With Changes in Left Ventricular Geometry and Function in the General Population: SHIP (Study of Health in Pomerania). Circ Cardiovasc Imaging. 2017;10(3):e005544. PubMedCrossRef
52.
Lee TC, Jin Z, Homma S, Nakanishi K, Elkind MSV, Rundek T, et al. Changes in left ventricular mass and geometry in the older adults: role of body mass and central obesity. J Am Soc Echocardiogr. 2019;32(10):1318–25. PubMedPubMedCentralCrossRef
53.
Oliver W, Matthews G, Ayers CR, Garg S, Gupta S, Neeland IJ, et al. Factors associated with left atrial remodeling in the general population. Circ Cardiovasc Imaging. 2017;10:2. CrossRef
54.
Hao Y, Ma X, Luo Y, Hu X, Pan X, Xiao Y, et al. Associations of serum adipocyte fatty acid binding protein with body composition and fat distribution in nondiabetic Chinese women. J Clin Endocrinol Metab. 2015;100(5):2055–62. PubMedCrossRef
55.
Reinehr T, Stoffel-Wagner B, Roth CL. Adipocyte fatty acid-binding protein in obese children before and after weight loss. Metabolism. 2007;56(12):1735–41. PubMedCrossRef
56.
Choi KM, Kim TN, Yoo HJ, Lee KW, Cho GJ, Hwang TG, et al. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocrinol (Oxf). 2009;70(4):569–74. CrossRef
57.
Furuhashi M, Hiramitsu S, Mita T, Omori A, Fuseya T, Ishimura S, et al. Reduction of circulating FABP4 level by treatment with omega-3 fatty acid ethyl esters. Lipids Health Dis. 2016;15:5. PubMedPubMedCentralCrossRef
58.
Furuhashi M, Mita T, Moniwa N, Hoshina K, Ishimura S, Fuseya T, et al. Angiotensin II receptor blockers decrease serum concentration of fatty acid-binding protein 4 in patients with hypertension. Hypertens Res. 2015;38(4):252–9. PubMedCrossRef
59.
Karpisek M, Stejskal D, Kotolova H, Kollar P, Janoutova G, Ochmanova R, et al. Treatment with atorvastatin reduces serum adipocyte-fatty acid binding protein value in patients with hyperlipidaemia. Eur J Clin Invest. 2007;37(8):637–42. PubMedCrossRef
60.
Furuhashi M, Hiramitsu S, Mita T, Fuseya T, Ishimura S, Omori A, et al. Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus. J Lipid Res. 2015;56(12):2372–80. PubMedPubMedCentralCrossRef
61.
Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007;447(7147):959–65. PubMedPubMedCentralCrossRef
Metadata
Title
Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study
Authors
Mei-Zhen Wu
Chi-Ho Lee
Yan Chen
Shuk-Yin Yu
Yu-Juan Yu
Qing-Wen Ren
Ho-Yi Carol Fong
Pui-Fai Wong
Hung-Fat Tse
Siu-Ling Karen Lam
Kai-Hang Yiu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2020
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-020-01167-5

Other articles of this Issue 1/2020

Cardiovascular Diabetology 1/2020 Go to the issue

Commentary

Type 2 diabetes and reduced exercise tolerance: a review of the literature through an integrated physiology approach

Original investigation

Impact of coronary collateralization on long-term clinical outcomes in type 2 diabetic patients after successful recanalization of chronic total occlusion

Review

The relationship between carotid disease and retinopathy in diabetes: a systematic review

Original investigation

Impact of type 2 diabetes mellitus on mid-term mortality for hypertrophic cardiomyopathy patients who underwent septal myectomy

Original investigation

Relationship between ABO blood groups and cardiovascular disease in type 1 diabetes according to diabetic nephropathy status

Original investigation

Hospitalization for heart failure incidence according to the transition in metabolic health and obesity status: a nationwide population-based study
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits