Association of plasma FGF21 levels with muscle mass and muscle strength in a national multicentre cohort study: Korean Frailty and Aging Cohort Study

Background despite of the beneficial effects of fibroblast growth factor (FGF) 21 in several metabolic diseases, the association of plasma FGF21 with muscle mass and muscle strength is still unclear. Methods a total of 386 community-dwelling older adults aged 70–84 years were analysed. Appendicular skeletal muscle mass was measured using dual-energy X-ray absorptiometry and normalised to the square of height (ASM/ht2). Muscle strength was assessed using the hand grip strength (HGS) test. The definitions of low muscle mass (LMM) and low muscle strength (LMS) were based on the Asian Working Group for Sarcopenia. Results plasma FGF21 was significantly lower in participants with LMM than in those with normal muscle mass (289.7 [192.4–448.3] vs. 345.6 [238.6–503.2] pg/ml, P = 0.008). In contrast, the LMS group had a significantly higher plasma FGF21 level than the normal muscle strength group (369.7 [244.4–591.1] vs. 309.7 [205.3–444.8] pg/ml, P = 0.006). In the partial correlation analysis, following adjustment for age, sex and body mass index, FGF21 levels had no significant association with ASM/ht2, but were negatively associated with HGS (r = −0.112, P = 0.029). Furthermore, after multivariate adjustment for confounding variables, the odds ratio for the risk of LMS was 2.32 (95% confidence interval 1.20–4.46) when comparing the highest with the lowest FGF21 quartile. Conclusions circulating FGF21 levels are negatively associated with muscle strength but are not independently correlated with muscle mass.

Increased Plasma FGF21 and Activated FGF21 Signaling in Adipose Tissue and Its Possible Association With Insulin Sensitivity in Specific GDM Subtype

Background: To study the discrepancy of the insulin sensitivity alteration pattern, circulating fibroblast growth factor (FGF21) levels and FGF21 signaling in visceral white adipose tissue (vWAT) of gestational diabetes mellitus (GDM) subtypes.Methods: 26 GDM women with either a predominant of insulin-secretion defect (GDM-dysfunction, n = 9) or insulin-sensitivity defect (GDM-resistance, n = 17)] and 13 normal glucose tolerance (NGT) women scheduled for caesarean-section at term were studied. Plasma and vWAT samples were collected at delivery.Results: The insulin sensitivity was improved from the 2nd trimester to delivery in the GDM-resistance group. Elevated circulating FGF21 concentration at delivery, increased FGF receptor 1c and decreased klotho beta gene expressions, enhanced ERK1/2 phosphorylation, and increased GLUT1, IR-B, PPAR-γ gene expressions in vWAT were found in the GDM-resistance group as compared with the NGT group. The circulating FGF21 concentration was negatively correlated with fasting blood glucose (r = -0.574, P < 0.001), and associated with the GDM-resistance group (r = 0.574, P < 0.001) in pregnant women at delivery. However, we observed no insulin sensitivity alteration in GDM-dysfunction and NGT groups during pregnancy. No differences of plasma FGF21 level and FGF21 signaling in vWAT at delivery were found between women in the GDM-dysfunction and the NGT group. Conclusions: Women with GDM heterogeneity exhibited different insulin sensitivity alteration patterns. The improvement of insulin sensitivity may relate to the elevated circulating FGF21 concentration and activated FGF21 signaling in vWAT at delivery in the GDM-resistance group.Trial registration: ChiCTR, ChiCTR 1900026735, registered 20 October 2019, https://www.chictr.org.cn/25/showproj.aspx?proj=44559

P–389 The relationship between serum hormone profiles and missed abortion in humans

Study question Are circulating profiles of metabolic-related hormones also associated with the missed abortion (MA) in humans? Summary answer Serum levels of fatty acid-binding protein–4 (FABP4) and fibroblast growth factor 21 (FGF21) are positively associated with MA. What is known already A cluster of endocrine hormones, including FABP4, FGF21, adiponectin, lipocalin–2 (LCN2), exhibit pleiotropic effects on regulating systematic metabolism. Serum levels of them are associated with gestational obesity and diabetes and affect pregnancy outcomes, however, the relationship between their circulating profiles and MA is under-investigated. Study design, size, duration 78 patients with MA and 86 healthy pregnant subjects matching on maternal age and body mass index (BMI) were nested from a prospective cohort in the Chinese population. Participants/materials, setting, methods Fasting serum samples from all participants were collected to test their serum levels of FGF21, FABP4, adiponectin, and LCN2 by enzyme-linked immunosorbent assay method (ELISA). Main results and the role of chance There were no significant differences in circulating profiles of adiponectin and LCN2 between MA patients and healthy pregnant subjects. By contrast, circulating levels of FGF21 and FABP4 were significantly and independently elevated in patients with MA relative to control cases even after adjusting confounding factors (for FGF21: MA: 28.96 ± 2.17 ng/ml; HP: 19.18 ± 1.12 ng/ml, P &lt; 0.001, for FABP4: MA: 152.50 ± 9.31 pg/ml; HP: 90.86 ± 4.14 pg/ml, P &lt; 0.001). Linear regression analysis showed, FGF21 raised every 10 pg/ml contributed to a 24% (95% CI: 15% - 34%) increase in the risk of MA, whereas the OR of FABP4 for the risk of MA was 1.052 (95% CI: 1.022 –1.088). Furthermore, using serum FGF21 level or FABP4 levels discriminated MA from healthy controls with an area under the operating characteristic’s curve (AUROC) of 0.81 (95% CI 0.76–0.92) and 0.70 (95% CI 0.62 - 0.78), respectively. Limitations, reasons for caution The study is limited by the sample size. In addition, our results were based-on Chinese population, whether it could be observed in other ethics group remain to be investigated. Meanwhile, the cause-effect relationship between increased serum FGF21 level and MA remains to be explored. Wider implications of the findings: Our data would suggest that serum levels of FGF21 and FABP4 are associated with MA. Moreover, circulating FGF21 levels may serve as a potential diagnostic biomarker for the recognition of M. Trial registration number IRB Ref. No.: KY201913

Does an increase in serum FGF21 level predict 28-day mortality of critical patients with sepsis and ARDS?

Background Sepsis may be accompanied by acute respiratory distress syndrome (ARDS) in patients admitted to intensive care units (ICUs). It is essential to identify prognostic biomarkers in patients with sepsis and ARDS. Objective Determine whether changes in the level of serum fibroblast growth factor 21 (FGF21) can predict the 28-day mortality of ICU patients with sepsis and ARDS. Methods Consecutive sepsis patients were divided into two groups (Sepsis + ARDS and Sepsis-only), and the Sepsis + ARDS group was further classified as survivors or non-survivors. Demographic data and comorbidities were recorded. The Sequential Organ Failure Assessment (SOFA) score and serum levels of cytokines and other biomarkers were recorded 3 times after admission. Multiple Cox proportional hazards regression was used to identify risk factors associated with 28-day mortality in the Sepsis + ARDS group. Multivariate receiver operating characteristic curve analysis was used to assess the different predictive value of FGF21 and SOFA. Results The Sepsis + ARDS group had a greater baseline SOFA score and serum levels of cytokines and other biomarkers than the Sepsis-only group; the serum level of FGF21 was almost twofold greater in the Sepsis + ARDS group (P < 0.05). Non-survivors in the Sepsis + ARDS group had an almost fourfold greater level of FGF21 than survivors in this group (P < 0.05). The serum level of FGF21 persistently increased from the baseline to the peak of shock and death in the non-survivors, but persistently decreased in survivors (P < 0.05). Changes in the serum FGF21 level between different time points were independent risk factors for mortality. No statistical difference was observed between the AUC of FGF21 and SOFA at baseline. Conclusion A large increase of serum FGF21 level from baseline is associated with 28-day mortality in ICU patients with sepsis and ARDS.

An association between fibroblast growth factor 21 and cognitive impairment in iron-overload thalassemia

Although an increased fibroblast growth factor 21 (FGF21) level was related to mild cognitive impairment (MCI) in metabolic syndrome patients, any association regarding FGF21 and MCI in thalassemia patients as well as mechanistic insight are questionable. Therefore, the objectives of this study were: (1) to investigate the prevalence and associative risk factors of MCI in thalassemia patients, (2) to evaluate the association between levels of FGF21 and MCI in thalassemia patients, and (3) to investigate brain FGF21 signaling in iron-overload thalassemia. Thalassemia patients were enrolled onto the study (n = 131). Montreal cognitive assessment (MoCA) was used to determine cognitive performance. Plasma FGF21 level was determined in all patients. Iron-overload β-thalassemic (HT) mice were used to investigate brain FGF21 level and signaling, the expression of synaptic proteins, and Alzheimer’s like pathology. We found that 70% of thalassemia patients developed MCI. FGF21 level was positively correlated with the MCI. Interestingly, brain FGF21 resistance, as indicated by increased brain FGF21 levels with impaired FGF21 signaling, was found in iron-overload HT mice. The reduced synaptic protein expression and increased Alzheimer’s like pathology were also observed. These suggest that FGF21 may play a role in MCI in thalassemia patients.

Does an Increase in Serum FGF21 Level Predict 28-day Mortality of Critical Patients with Sepsis and ARDS?

BackgroundSepsis may be accompanied by acute respiratory distress syndrome (ARDS) in patients admitted to intensive care units (ICUs). It is essential to identify prognostic biomarkers in patients with sepsis and ARDS.ObjectiveDetermine whether changes in the level of serum fibroblast growth factor 21 (FGF21) can predict the 28-day mortality of ICU patients with sepsis and ARDS.MethodsConsecutive sepsis patients were divided into two groups (Sepsis+ARDS and Sepsis-only), and the Sepsis+ARDS group was further classified as survivors or non-survivors. Demographic data and comorbidities were recorded. The Sequential Organ Failure Assessment (SOFA) score and serum levels of cytokines and other biomarkers were recorded 3 times after admission. Multiple Cox proportional hazards regression was used to identify risk factors associated with 28-day mortality in the Sepsis+ARDS group.ResultsThe Sepsis+ARDS group had a greater baseline SOFA score and serum levels of cytokines and other biomarkers than the Sepsis-only group; the serum level of FGF21 was almost 2-fold greater in the Sepsis+ARDS group (P<0.05). Non-survivors in the Sepsis+ARDS group had an almost 5-fold greater level of FGF21 than survivors in this group (P<0.05). The serum level of FGF21 persistently increased from the baseline to the peak of shock and death in the non-survivors, but persistently decreased in survivors (P<0.05). Changes in the serum FGF21 level between different time points were independent risk factors for mortality.ConclusionA large increase of serum FGF21 level from baseline is associated with 28-day mortality in ICU patients with sepsis and ARDS.

Association between serum fibroblast growth factor 21 level and sight-threatening diabetic retinopathy in Chinese patients with type 2 diabetes

IntroductionWe conducted this cross-sectional study to explore the relationship between serum fibroblast growth factor 21 (FGF21) level and sight-threatening diabetic retinopathy (STDR).Research design and methodsA total of 654 patients with type 2 diabetes were recruited. Diabetic retinopathy (DR) was evaluated by the bilateral retinal photography, and patients were assigned into groups of no DR (NDR) (n=345, 52.75%), non-sight-threatening diabetic retinopathy (NSTDR) (n=207, 31.65%), involving patients with mild or moderate non-proliferative retinopathy (NPDR) and STDR (n=102, 15.60%), including those with severe NPDR or proliferative diabetic retinopathy (PDR). Serum FGF21 levels were quantified by a sandwich ELISA. Patients were divided into quartiles according to their serum FGF21 level.ResultsThere was a significant difference in serum FGF21 level among the three groups of patients (p<0.01). Compared with other quartiles (Q1–Q3), the patients in Q4 had a higher prevalence of DR and STDR (p<0.05). Compared with Q1, a positive association was observed between serum FGF21 level and DR in Q3 and Q4 (p<0.01). After adjusting for age, gender and other risk factors, serum FGF21 level in Q4 was found to be associated with increased risk of DR and STDR (p<0.01). Serum FGF21 level was noted as an independent risk factor for DR and STDR (p<0.01). Serum FGF21 level >478.76 pg/mL suggested the occurrence of DR and that level >554.69 pg/mL indicated STDR (p<0.01).ConclusionsSerum FGF21 level was a biomarker for the risk of developing DR or STDR. The risk of STDR increased when the serum FGF21 level of patients with type 2 diabetes was >554.69 pg/mL.

P1395FIBROLAST GROWTH FACTOR 21 CORRELATES POSITIVELY WITH AND PREDICTS TO OSTEOPOROSIS IN HEMODIALYSIS PATIENTS

Background and Aims Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) has been recognized as a common complication and arises early in the course of CKD. Osteoporosis can be one form of renal osteodystrophy, one component of the bone abnormalities of CKD-MBD. Fibroblast growth factor 21 (FGF21) is increased progressively with a decline of renal function and higher FGF21 levels predict high all-cause mortality in hemodialysis patients. In recent studies, FGF21 has been approved to exert an inverse effect on bone mineral density. Hence, our study was performed to investigate the relationship and role of FGF21 in osteoporosis in our hemodialysis (HD) patients cohort. Method We screened HD patients in Nanjing Zhongda Hospital and The First People’s Hospital of Changzhou according to a strict inclusion criteria and exclusion criteria. We recorded demographic information, blood data before dialysis and serum FGF21, FGF23 levels and measured the CT-attenuation values (in Hounsfield units (HU)) of trabecular bone in L1 on axial images to evaluate the severity of osteoporosis. We used univariate analyses to compare the differences between two groups. Meanwhile, bivariate correlation analyses were performed to assess the correlation of L1 attenuation with serum FGF21, FGF23 and other clinical parameters. Stepwise multivariate linear regression analyses were employed to evaluate variables independently associated with attenuation values. We constructed ROC curves to calculate the AUC and compared the prognostic value of every independently associated factor or united factor to osteoporosis. All analyses were two-tailed, and a P &lt; 0.05 was considered to be statistically significant. SPSS Software, version 18.0 was used for all statistical analyses. Results 339 HD patients from two big HD centers in China that met our standards were screened. The mean age of HD patients was 56.79 ± 15.60 years. 339 HD patients were divided into two groups osteoporosis (n = 98) and non-osteoporosis (n = 241) on the basis of HU level (L1 attenuation ≤ 135 HU). Remarkably, serum FGF21 were higher in osteoporosis compared to non- osteoporosis in HD patients (median 640.86 pg/ml vs. 245.46 pg/ml, P &lt; 0.01). We also divided HD patients into two groups according to tertiles of serum FGF21 levels. Moreover, attenuation levels were negative associated independently with serum FGF21 (r=-0.136, P&lt;0.05). To evaluate the different values of independent associated or united factors in predicting osteoporosis, receiver operating characteristic (ROC) curves was constructed. The area under the curve (AUC) for FGF21 combined with age yielded a marked increment (AUC=0.836, P=0.000) with a good sensitivity (93.8%). Conclusion In conclusion, elevated FGF21 level has a positive relationship with the incidence of osteoporosis in HD patients. Simultaneously, FGF21 in combination with age can be a predictive parameter of osteoporosis in HD patients.