Close Association of Serum Fibroblast Growth Factor (FGF) 23, but Not 25(OH)Vitamin D3, with Diabetic Nephropathy in Type 2 Diabetic Subjects

Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.

Download Full-text

Inverse Association of Serum Fibroblast Growth Factor 19 and Atherogenic Index of Plasma in Type 2 Diabetic Patients

10.21203/rs.2.24087/v1 ◽

2020 ◽

Author(s):

Wangshu Liu ◽

Tianli Xu ◽

Mengjie Tang ◽

Xue-Qin Wang ◽

Jianbin Su ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Atherogenic Index ◽

Diabetic Patients ◽

Fibroblast Growth ◽

Type 2 Diabetic Patients ◽

Atherogenic Index Of Plasma ◽

Fibroblast Growth Factor 19 ◽

Type 2 Diabetic

Abstract BackgroundWe aimed to explore the relationship between serum fibroblast growth factor 19 (FGF19) and the atherogenic index of plasma (AIP) in type 2 diabetic patients.MethodsSerum FGF19 levels and lipid profiles were measured in 200 patients with type 2 diabetes (T2D). The levels of serum FGF19 were measured by ELISA. Lipid profiles were measured by enzymatic analysis. AIP and NAFLD fibrosis scores were calculated.ResultsT2D patients showed a significant decreasing trend of FGF19 concentrations depending on the tertiles of AIP (p for trend < 0.05). Simultaneously, the AIP level was closely related to the serum FGF19 level (p < 0.05). Furthermore, after adjusting for age, sex, duration, BMI, hypertension, and diabetic treatment, the correlation was still significant (p < 0.01), and it remained significant even after further adjusting for non-alcoholic fatty liver disease (NAFLD) and NAFLD fibrosis score (NFS) (p < 0.01). However, when stratified by BMI, AIP was positively correlated with FGF19 in normal-weight and overweight T2D patients but not in obese T2D subjects. After adjusting for sex, age, BMI, duration, hypertension, HbA1c, 2hPG, HOMA-IR, AIP, antidiabetic treatments, NAFLD and NFS via multiple stepwise linear regression, AIP was an independent factor affecting serum FGF19 concentrations (SE = 0.238, β = -0.290, p < 0.01).ConclusionsSerum FGF19 levels might be a good predictor for atherosclerosis and cardiovascular disease in T2D patients, especially among non-obese patients; serum FGF19 levels were significantly inversely associated with AIP.

Download Full-text

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

Cardiovascular Diabetology ◽

10.1186/s12933-020-01135-z ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Martin H. Sørensen ◽

Annemie S. Bojer ◽

Niklas R. Jørgensen ◽

David A. Broadbent ◽

Sven Plein ◽

...

Keyword(s):

Type 2 Diabetes ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Kidney Function ◽

Fibroblast Growth Factor 23 ◽

Left Ventricular ◽

Fibroblast Growth ◽

Cardiovascular Morbidity And Mortality ◽

Fgf 23

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

Download Full-text