Fatty Acid Binding Protein 4-A Circulating Protein Associated with Peripheral Arterial Disease in Diabetic Patients.

Abdelrahman Zamzam,Muzammil H Syed,Elisa Greco,Krishna K Singh,Shubha Jain,Rawand Abdin,Thomas L Forbes,Mark Wheatcroft,Ori Rotstein,Hamzah Khan,Mohammad Qadura

doi:10.3390/jcm9092843

Abstract

Diabetic patients with peripheral arterial disease (PAD) often suffer from poor clinical outcomes such as limb-loss. Fatty acid binding protein 4 (FABP4) is mainly expressed by adipocytes and is known to play a significant role in the development of atherosclerosis. In this study, we sought to investigate whether FABP4 is associated with PAD in patients with type 2 diabetes mellitus (DM). FABP4 plasma levels were studied in 119 diabetic patients with PAD (DM-PAD) and 49 diabetic patients without PAD (DM-noPAD) presenting to St. Michael’s Hospital between October 2017 and September 2018. Levels of FABP4 in DM-PAD patients (23.34 ± 15.27 ng/mL) were found to be over two-fold higher than the levels in DM-noPAD patients (10.3 ± 7.59 ng/mL). Regression analysis demonstrated a significant association between FABP4 levels and DM-PAD after adjusting for age, sex, prior history of coronary arterial disease and white blood cells count (OR, 2.77; 95% CI, 1.81–4.31; p-value = 0.001). Relative to DM-noPAD controls, plasma FABP4 levels in DM-PAD patients were noted to be inversely correlated with the ankle brachial index (ABI; r= −0.374, p-value < 0.001). The diagnostic ability of FABP4 was investigated using receiver operator curves (ROC) and area under the curve (AUC) analysis. FABP4 had an AUC of 0.79, which improved to 0.86 after adjusting for age, sex and prior history of coronary arterial disease. This raises a possibility of utilizing FABP4 as a biomarker for diagnosing PAD in diabetic patients.

Highlights

Type 2 diabetes mellitus (DM) is a serious chronic condition that affects over 400 million patients globally [1]
We found that Fatty acid binding protein 4 (FABP4) levels were independently and strongly associated with DM-peripheral arterial disease (PAD) status, despite adjusting for age and sex (OR, 2.74; 95% confidence intervals (95% CI), 1.80–4.18; p-value = 0.001)
Hemodynamic Association between FABP4 and DM-PAD We studied the hemodynamic correlation between FABP4 and ankle brachial index (ABI) to better understand the associaWtioensbtuetdwieedenthFeAhBePm4oadnydnDamMic-PcAoDrr.eRlaetliaotnivbeettowteheenDFMAB-nPo4PaAnDd pAaBtiIentotsb, petltaesrmuanFdAerBsPta4nldevtheles of DMas-sPoAciDatisounbbjeecttwsewenerFeAinBvPe4rasneldyDcoMr-rPeAlaDte.dRweliatthivAe BtoI t(hre=D−M0.-3n7o4P,ApD-vaplautiee

Summary

Introduction

Type 2 diabetes mellitus (DM) is a serious chronic condition that affects over 400 million patients globally [1]. Patients with DM are at an increased risk of developing various cardiovascular diseases, such as peripheral arterial disease (PAD) [2]. PAD is caused by the development of atherosclerotic plaques within the arterial vessels supplying blood to the limbs, resulting in lower limb claudication, rest pain or even tissue loss (in symptomatic patients). Patients suffering from both DM and PAD concurrently are at a higher risk of having cardiovascular events, lower limb amputations, and death [4,5,6]. The pathophysiology by which DM causes changes in lower limb vasculature and PAD is complex. Studies have proposed that chronic glycemic stress, chronic low-grade inflammation, and impaired vascular tissue repair are a few of the pathways that may be involved in the development of PAD [7,8]

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Conclusion