Abstract
BackgroundFibroblast growth factor 21 (FGF21), a glucose and lipid metabolic regulator, has recently been demonstrated to be associated with cardiovascular diseases (CVD) such as carotid atherosclerosis, coronary heart disease and carotid artery plaques. However, the relationship between circulating FGF21 and subclinical atherosclerosis or atherosclerosis of other arteries such as the femoral and iliac artery remains unclear. In this study, we evaluated the association of serum FGF21 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.MethodsSerum FGF21 levels were detected by enzyme-linked immunosorbent assay in 212 newly diagnosed type 2 diabetic patients without clinical symptoms of atherosclerosis or cardiovascular diseases. IMT of the carotid, femoral, and iliac arteries were measured by high-resolution B-mode ultrasound to determine the presence of subclinical atherosclerosis, which was defined as having an IMT > 1.0 mm and/or plaque on one or more of the three arteries without any clinical manifestations. The relationship between serum FGF21 levels and subclinical atherosclerosis was analyzed.ResultsSerum FGF21 levels were significantly higher in patients with subclinical atherosclerosis compared to those without [261.3 (135.1–396.4) versus 144.9 (95.9–223.0) ng/L, P < 0.001]. These differences were also observed in both men and women with subclinical atherosclerosis compared to their respective groups without [men: 243.2 (107.6–337.0) versus 136.8 (83.6–212.8) ng/L, P = 0.048; women: 292.4 (174.2–419.9) versus 160.4 (115.3–258.5) ng/L, P = 0.001]. Moreover, serum FGF21 levels showed a significantly positive correlation with carotid IMT in women (r = 0.23, P = 0.018) and with iliac IMT in both genders (women: r = 0.27, P = 0.005; men: r = 0.22, P = 0.024). Multiple logistic regression analysis further showed that serum FGF21 was an independent impact factor for subclinical atherosclerosis in patients with type 2 diabetes.ConclusionsSerum FGF21 is elevated in newly diagnosed type 2 diabetes, and positively correlates with carotid and iliac lesions in patients with subclinical atherosclerosis, especially in women. High levels of FGF21 may be a compensatory reaction to offset atherosclerosis.
Highlights
Fibroblast growth factor 21 (FGF21), a glucose and lipid metabolic regulator, has recently been demonstrated to be associated with cardiovascular diseases (CVD) such as carotid atherosclerosis, coronary heart disease and carotid artery plaques
Despite the multiple salutatory effects of FGF21 on glucose and lipid metabolism in animals, circulating FGF21 levels are elevated in obese subjects [5, 6] and patients with impaired glucose tolerance [7], type 2 diabetes mellitus [5, 7, 8], dyslipidemia [9], and nonalcoholic fatty liver disease (NAFLD) [10, 11]
Serum FGF21 levels positively correlated with fasting glucose and TG (P = 0.034 and P = 0.042, respectively, Table 2)
Summary
Fibroblast growth factor 21 (FGF21), a glucose and lipid metabolic regulator, has recently been demonstrated to be associated with cardiovascular diseases (CVD) such as carotid atherosclerosis, coronary heart disease and carotid artery plaques. A growing body of evidence demonstrates that FGF21 is an important metabolic regulator with multiple beneficial effects on glucose and lipid homeostasis in animals [3, 4]. Despite the multiple salutatory effects of FGF21 on glucose and lipid metabolism in animals, circulating FGF21 levels are elevated in obese subjects [5, 6] and patients with impaired glucose tolerance [7], type 2 diabetes mellitus [5, 7, 8], dyslipidemia [9], and nonalcoholic fatty liver disease (NAFLD) [10, 11]. It has been proposed that the elevated level of FGF21 (a condition termed “hyper-FGF21-nemia”) in obese subjects is due to a decrease in the number of responsive FGF21 receptors on target cells, a phenomenon known as FGF21 resistance [12]
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