Prognostic Utility of Fatty Acid-Binding Protein 4 in Patients with Type 2 Diabetes and Acute Ischemic Stroke

Abstract

The role of fatty acid-binding proteins (FABPs) in atherosclerosis has been investigated. The aim of this study was to verify the hypothesis that higher levels of serum fatty acid-binding protein 4 (FABP4) could be a prognostic factor in Chinese patients with type 2 diabetes (T2DM) and acute ischemic stroke (AIS). From September 2015 to August 2016, consecutive first-ever AIS patients combined with T2DM were included in this study. FABP4, NIH stroke scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcomes within 3 months. Multivariate analyses were performed using logistic regression models. We measured FABP4 in 329 patients. The median age of patients included in this study was 63 (IQR, 56-72) years and 45.9% were women. FABP4 serum levels were obtained at a median of 8.5 h (IQR, 4.0-14.0 h) after the stroke onset with a median value of 21.4 ng/ml (IQR, 15.6-28.2 ng/ml). In multivariable models, FABP4 remained an independent stroke severity predictor with an adjusted OR of 1.05 (95% CI, 1.02-1.09). In multivariate models comparing the third (odd ratio (OR), 2.25; 95% confidence interval (CI), 1.59-3.54) and fourth quartiles (OR, 3.75; 95% CI, 2.48-5.03) against the first quartile of the FABP4, levels of FABP4 were associated with poor functional outcome. At 3 months, 38 patients (11.6%; 95%CI, 8.1-15.0%) had died. The mortality distribution across the FABP4 quartiles ranged between 3.7% (first quartile) and 20.7% (fourth quartile). Elevation of FABP4 is associated with an increased risk of death and poor functional outcome events in patients with type 2 diabetes and acute ischemic stroke and is independent of other established clinical risk predictors and biomarkers.

Associations between Fatty Acid-Binding Protein 4–A Proinflammatory Adipokine and Insulin Resistance, Gestational and Type 2 Diabetes Mellitus

“…It has been reported that increased circulating FABP4 levels are associated with obesity, insulin resistance, T2DM, cardiovascular disorders, arterial hypertension, cardiac dysfunction, kidney damage, fatty liver disease, and atherosclerosis [10,29,31,32,39,40,41,42]. Increased FABP4 concentrations were found in obese subjects and were positively correlated with waist circumference, blood pressure, and insulin resistance [40].…”

“…Increased FABP4 production could contribute to macrophage activity, possibly by activation of inflammatory pathways, resulting in inflammation [42]. An alternative hypothesis, more in line with the published evidence, is that the elevated circulating FABP4 reflects the increased cellular production in both adipocytes and macrophages in response to greater lipid availability, with increased Kupffer cell production of FABP4 triggering an increased inflammatory response [42,54].…”

“…High levels of FABP4 may contribute to adverse prognosis via the induction of endoplasmic reticulum stress in macrophages and upregulation of pro-inflammatory cytokine production. Indeed, FABP4 modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1 [42,56]. FABP4 is also implicated in modulating the eicosanoid balance by affecting both cyclooxygenase 2 (COX2) activity and leukotriene A4 (LTA4) stability, and upregulates uncoupling protein 2 (UCP2); all these processes influence macrophage function and adipose tissue inflammation.…”

Natural genetic variation in Stim1 creates stroke in the spontaneously hypertensive rat

“…The Fabp4 IgG signal was much reduced in the SHR-A3(Stim1-B2) congenic line. Fabp4 is a marker of stroke risk [45], a prognostic indicator of stroke outcome [46,47] and is a proangiogenic factor expressed in vascular endothelial cells [48]. The HuProt array poses limitations: first, the arrayed proteins are not rat proteins.…”

The association between serum adipocyte fatty acid–binding protein and 3-month disability outcome after aneurysmal subarachnoid hemorrhage

“…Further, Tso et al [12] showed that serum FABP4 was independently related to stroke (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.50-2.94; P < 0.001), and a high serum level was associated with increased risk of 3-month mortality in ischemic stroke subjects (OR 2.65, 95% CI 1.18-5.96; P = 0.018). High levels of FABP4 were also significantly associated with stroke risk and severity, independent from other risk factors [13], while elevated serum FABP4 levels were associated with poor prognosis in ischemic stroke patients with type 2 diabetes [14].…”