Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

Masato Furuhashi; Ichiro Sakuma; Takeshi Morimoto; Yukimura Higashiura; Akiko Sakai; Megumi Matsumoto; Mio Sakuma; Michio Shimabukuro; Takashi Nomiyama; Osamu Arasaki; Koichi Node; Shinichiro Ueda

doi:10.3389/fendo.2020.575557

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

Front Endocrinol (Lausanne). 2020 Sep 23:11:575557. doi: 10.3389/fendo.2020.575557. eCollection 2020.

Authors

Affiliations

¹ Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
² Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan.
³ Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan.
⁴ Department of Diabetes, Endocrinology and Metabolism, Fukushima Medical University, Fukushima, Japan.
⁵ Department of Diabetes, Metabolism and Endocrinology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan.
⁶ Department of Cardiology, Tomishiro Central Hospital, Tomigusuku, Japan.
⁷ Department of Cardiovascular Medicine, Saga University, Saga, Japan.
⁸ Department of Pharmacology and Therapeutics, University of the Ryukyus, Okinawa, Japan.

Abstract

Objective: Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus. Methods: As a sub-analysis study of the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial, 256 patients (male/female: 146/110, age: 68 ± 10 years) with type 2 diabetes mellitus and dyslipidemia who were receiving statin therapy were recruited. Patients who had been treated with a thiazolidinedione were excluded. Results: Several drugs which may modulate FABP4 levels including statins, dipeptidyl peptidase-4 inhibitors and angiotensin II receptor blockers had been administered in 100, 81, and 51% of the recruited patients, respectively. The level of FABP4, but not that of FABP5, was significantly higher in females than in males. Multivariable linear regression analysis demonstrated that waist circumference (β = 0.21), estimated glomerular filtration rate (β = -0.31), triglycerides (β = 0.16), and FABP5 (β = 0.39) were independent predictors of FABP4 level after adjusting age and sex. On the other hand, FABP5 level was independently associated with levels of FABP4 (β = 0.57) and high-density lipoprotein (HDL) cholesterol (β = -0.12). Conclusions: Concentrations of FABP4 and FABP5 are independent predictors of each other in patients with type 2 diabetes mellitus. There are distinct independent associations of FABP4 with renal dysfunction, adiposity and hypertriglyceridemia and there is a distinct independent association of FABP5 with a low HDL cholesterol level in type 2 diabetic patients with dyslipidemia at high risks for cardiovascular disease who are receiving statin therapy.

Keywords: adipokine; diabetes mellitus; dipeptidyl peptidase-4 inhibitor; fatty acid-binding protein; stain.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adiposity
Aged
Biomarkers / blood
Cardiovascular Diseases / drug therapy
Cardiovascular Diseases / physiopathology*
Diabetes Mellitus, Type 2 / drug therapy
Diabetes Mellitus, Type 2 / physiopathology*
Dyslipidemias / drug therapy
Dyslipidemias / physiopathology*
Fatty Acid-Binding Proteins / blood*
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
Hypertriglyceridemia / blood
Hypertriglyceridemia / diagnosis*
Hypertriglyceridemia / epidemiology
Kidney Diseases / blood
Kidney Diseases / diagnosis*
Kidney Diseases / epidemiology
Male

Substances

Biomarkers
FABP4 protein, human
FABP5 protein, human
Fatty Acid-Binding Proteins
Hydroxymethylglutaryl-CoA Reductase Inhibitors