Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics

Abstract

Background The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes. Methods In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m2 were excluded. Results Median (Q1–Q3) FGF-23 was 74 (58–91) ng/L. Patients with FGF-23 above the median had lower MBF during stress (2.3 ± 0.9 vs. 2.7 ± 0.9 ml/min/g, P = 0.001) and lower overall myocardial perfusion reserve (MPR) (2.7 ± 0.8 vs. 3.3 ± 1.1, P < 0.001). LV mass (143 ± 40 vs. 138 ± 36 g, P = 0.04) and E/e* (8.5 ± 3.2 vs. 7.6 ± 2.7, P = 0.04) were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, R2 = 0.11) and increased E/e* (P < 0.01, R2 = 0.07). FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57–86) vs. 80 (60–98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues. Conclusions In patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23. Clinical trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT02684331. Date of registration: February 18, 2016

Multiparametric CMR imaging of myocardial structure and function changes in diabetic mini-pigs with preserved LV function: a preliminary study

“…We also found that LVM was increased after the modeling of 1.5 months. Similar results were reported by Sorensen et al [ 18 , 19 ] in a large cohort of patients examined with CMR. In their entire cohort, Sorensen et al found that LVM was generally higher in these patients with FGF-23 above the median.…”

RETRACTED: Mitofusin-2 Enhances Mitochondrial Contact With the Endoplasmic Reticulum and Promotes Diabetic Cardiomyopathy

“…Mitochondria are remarkably dynamic organelles that perform diverse yet interconnected functions by producing ATP and multiple biosynthetic intermediates that participate in cellular stress responses, autophagy, and apoptosis ( Ma et al, 2020 ; Pflüger-Müller et al, 2020 ; Sawashita et al, 2020 ). The mitochondrial membrane potential is a key indicator of mitochondrial activity as it reflects the processes of electron transport and oxidative phosphorylation, which enable ATP production ( Schinner et al, 2020 ; Sørensen et al, 2020 ). High-glucose conditions have been shown to disrupt the mitochondrial membrane potential and increase the ATP levels ( Nesti et al, 2020 ).…”

Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease

“…In a cross-sectional study in 71 patients with T1DM and early DKD, FGF-23 levels correlated with diastolic cardiac dysfunction [ 82 ]. In a larger cross-sectional study in 246 patients with Τ2DM, increased serum levels of FGF-23 were also associated with cardiac diastolic dysfunction and with reduced myocardial perfusion reserve [ 83 ]. In another cross-sectional study in 545 African American patients with T2DM, FGF-23 concentrations were associated with the extent of coronary artery calcification [ 84 ].…”