FGF23 in Type 2 Diabetic Patients: Relationship With Bone Metabolism and Vascular Disease

Abstract

The relationship between fibroblast growth factor (FGF) 23 and vascular disease is well established in chronic kidney disease (CKD). Regarding serum FGF23 and bone fragility, there is contradictory data. Type 2 diabetes (T2D) is associated with higher rates of cardiovascular disease and fractures despite high bone mineral density (BMD), so the evaluation of FGF23 and its relationship with bone and cardiovascular disease in T2D is of interest. Our hypothesis was that serum FGF23 may be related to cardiovascular disease and bone metabolism (BMD, osteoporosis, and fractures) in T2D.We performed a cross-sectional study including 68 T2D subjects and 45 subjects without diabetes. We analyzed the relationship between circulating FGF23, bone metabolism, cardiovascular events, and intima-media thickness (IMT).There were no differences in FGF23 according to group. In the entire cohort, subjects with prevalent fracture and osteoporosis had lower FGF23 (20.9 6 8.3 vs. 51.4 6 38.9 pg/mL and 29.5 6 15.6 vs. 52.4 6 40.6 pg/mL, P , 0.05). In T2D, serum FGF23 was related to serum phosphorus (r 5 0.484), lumbar spine T-score (r 5 0.300), and femoral neck T-score (r 5 0.252) and was inversely related to age (r 5 20.496) (P , 0.05 for all). Differences according to osteoporosis, abnormal IMT, and diabetic nephropathy are shown in Fig. 1. In T2D, after linear regression analysis the main determinants of serum FGF23 were age Our results showed a stronger correlation between FGF23 and BMD than previously found in elderly nondiabetic males (1,2). Serum FGF23 may reflect the osteocyte number, and T2D subjects have higher BMD. On the other hand, a different relationship between FGF23 and parathyroid hormone in diabetes has been reported apart from the presence of CKD (3), which may indicate a differentiated regulation and possibly different effects of FGF23 on bone metabolism in T2D compared with nondiabetic populations.In our study, subjects with previous fractures have lower FGF23 concentrations, but no differences in T2D were found. Circulating FGF23 has been linked to fracture risk (4), although in another study FGF23 and hip fracture risk was not related (2). We consider that the relationship between FGF23 and fracture risk is not established.T2D patients with abnormal IMT had lower FGF23, and abnormal IMT remained associated with FGF23 after linear regression analysis. However, FGF23 and established cardiovascular disease or aortic calcification was not related. Our findings may indicate a role in the development of atherosclerosis in T2D. Supporting the association between FGF23 and preclinical vascular disease, higher FGF23, even within the normal range, is independently associated with impaired vasoreactivity and increased arterial stiffness in the general population (5).In summary, serum FGF23 is related to BMD and preclinical vascular disease in T2D patients. Our study suggests that effects of FGF23 in T2D may differ from other populations, although it must be confirmed in larger studies.

Protective effects of water fraction of Fructus Ligustri Lucidi extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice

“…The similar results were indicated in type 2 diabetic patients with increased risk of fracture (Reyes-Garcia et al, 2014). It was found in this study that the treatment with water fraction of Fructus Ligustri Lucidi (FLL) ethanol extract (WF-EE) resulted in the increased level of both calcium and FGF-23 in serum, which could be, at least partially, attributed to the regulation of WF-EE on serum level of parathyroid hormone (PTH) in diabetic mice, since FGF-23 is well known to be stimulated by PTH (Zanchi et al, 2013) and positively correlates with circulating calcium level (David et al, 2013).…”

Impact of Osteocalcin Level on Vascular Calcification in Type 2 Diabetics in Relation to Fibroblast Growth Factor-23(FGF-23)

“…As observed in this study (figure-6), serum FGF-23 level was significantly elevated in diabetic patients with cardiovascular disease (group A) as well as in diabetic patients without cardiovascular disease (group B) as compared to the control (P<0.01).The increased levels in T2DM could be attributed to: Firstly: there is a strong relation between the FGF-23 and the BMD in T2DM patients. The serum level of FGF-23 may give an idea about the number of osteocytes and a higher BMD can be found in T2DM as agreed with Reyes-Garcia et al study (59) .…”

“…In addition, the higher FGF-23 level was associated with increased arterial stiffness as demonstrated in patients with T2DM (59) and even in the general population (67) . Furthermore, Voigt et al study reported that the FGF-23 was detected in the calcified carotid atherosclerotic lesion from individuals with normal renal function (68) .…”

Is fibroblast growth factor 23 a new cardiovascular risk marker in gestational diabetes?

“…In our study, FGF23 was correlated with insulin resistance. A recent study reported that serum FGF23 was associated with bone mineral density and preclinical vascular disease in patients with T2DM and their findings suggested that influences of FGF23 in these patients might be different from the effects in other populations (39).…”