Plasma Fatty Acid-Binding Protein 4 Increases with Renal Dysfunction in Type 2 Diabetic Patients without Microalbuminuria

Abstract

Background: Fatty acid–binding protein 4 (FABP4) has been linked to metabolic syndrome development, diabetes, and arteriosclerosis, but the role of FABP4 in target organ damage has not been assessed. We evaluated whether plasma FABP4 is associated with renal dysfunction in type 2 diabetic patients. Methods: In 263 individuals (161 type 2 diabetic patients and 102 healthy nondiabetic controls), we analyzed the correlation between FABP4 and creatinine or glomerular filtration index (MDRD-GFR) regarding the presence or absence of microalbuminuria. Patients with severe chronic kidney disease (MDRD-GFR <30 mL/min/1.73 m2) or albuminuria were not included. Results: FABP4 concentrations were higher in diabetic patients with MDRD-GFR <60 mL/min/1.73 m2 (P <0.001). We observed a significant, direct correlation between FABP4 and creatinine (r = 0.446, P <0.001) and an inverse correlation between FABP4 and MDRD-GFR (r = −0.511, P <0.001) in type 2 diabetic patients, but not in nondiabetic individuals. These correlations were sustained when only those patients without microalbuminuria were analyzed (r = 0.414, P <0.001 and r = −0.510, P <0.001, respectively). Type 2 diabetic patients with FABP4 in the highest tertile compared with those in the lower tertiles had increased adjusted odds ratios for moderate renal dysfunction [7.5 (95%CI 1.8–30.7), P = 0.005 and 15.3 (3.1–76.4), P = 0.001; respectively], independent of microalbuminuria. Conclusions: High FABP4 plasma concentrations are associated with high plasma creatinine and low MDRD-GFR in patients with type 2 diabetes even in the absence of microalbuminuria or clinically relevant alterations of creatinine and MDRD-GFR values. FABP4 concentrations should be taken into consideration as an early marker of kidney damage in patients with type 2 diabetes.

Relation of Plasma Fatty Acid Binding Proteins 4 and 5 With the Metabolic Syndrome, Inflammation and Coronary Calcium in Patients With Type-2 Diabetes Mellitus

“…Despite this limitation, we chose CAC scores as our measure of subclinical atherosclerosis, because they are strong, independent predictors of CVD, 25 including in patients with diabetes. 26 Risk factor associations with CAC in T2DM can be confounded by the presence of chronic kidney disease, 27 but this was not the case in our analysis, likely because >95% of the PDHS sample have estimated glomerular filtration rates >60 ml/min.…”

A Protein Profile of Visceral Adipose Tissues Linked to Early Pathogenesis of Type 2 Diabetes Mellitus

“…serum/plasma, urine, muscle, or liver; supplemental Table S9). A higher serum FABP4 level was linked to obesity, insulin resistance, and T2DM (62,63). The amount of the serum C1q-adiponectin complex showed a significant correlation with coronary artery disease in Japanese T2DM subjects (64).…”

Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

“…Furthermore, elevated serum concentration of FABP4 has been shown to be associated with obesity, insulin resistance, type 2 diabetes mellitus, hypertension, cardiac dysfunction, renal dysfunction, dyslipidemia, atherosclerosis, and cardiovascular events ( 8,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However, little is known about the modulation of serum FABP4 level by therapeutic drugs including antidiabetic agents except for thiazolidinedione ( 25 ).…”