Association Of Fibroblast Growth Factor 21 With β-cell Function And C-reactive Protein In Chinese Individuals Under Different Glucose Tolerance Statuses

Objective: The aim of the present study was to investigate the level of serum FGF21 in individuals under different glucose tolerance statuses and explore the association of FGF21 with islet β cell function and inflammatory cytokine(serum C-reactive protein,CRP).Methods:1 Subjects: A total of 128 subjects who received 75 g oral glucosetolerance-test(64 male, average 54.55±11.22 years, 64 female, average 56.88±8.79 years) were recruited from March 2014 to November 2014 at The Third Hospital of Hebei Medical University. The protocol was approved by the Institutional Human Subjects Review Committee of Hebei Medical University. All subjects provided written informed consent to participate in this study. Participants with type 1 diabetes or specific type of diabetes, acute complications of diabetes(DKA, HHS, DLA), tumor, immune system disease, connective tissue disease, severe organ dysfunction(including liver, heart, kidney and adrenal gland), polycystic ovarian syndrome(PCOS), and epididymitis were excluded. In addition, participants who were currently receiving medicine treatment which could be affecting serum FGF21 or/and CRP levels(such as fenofibrate, glucocorticoids), were also excluded. All subjects were classified into 3 groups based on the World Health Organization(WHO) 1999 diagnostic criteria for diabetes, including normal glucose tolerance(NGT) group(n=33), impaired glucose regulation(IGR) group(n=50), and type 2 diabetes mellitus(T2DM) group(n=45).2 Methods: Human body parameters including height, weight, systolic blood pressure(SBP), and diastolic blood pressure(DBP) were measured by the same investigator. Body mass index(BMI) was calculated. Biochemical parameters were measured as follow: venous blood samples were collected from all subjects who had been fasting over 8h overnight. Serum triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by automatic biochemistry analyzer(OLYMPUSAU-2700, Japan). Blood glucose was measured by glucose oxidase method. Insulin(INS) was measured by radioimmunoassay(RIA). Enzyme-linked immunosorbent assay(ELISA) kits were used to measure serum FGF21 and CRP. The intra and inter-assay coefficients of variation(CV) were <10% and <12%, respectively. The indexes were calculated as follow: AUCINS(Area under the curve) =1/4S0+1/2S30+3/4S60+S120+1/2S180, HOMA-IR(Homeostasis model assessment-insulin resistance) =(FPG in mmol/L)×(FINS in m IU/L)/22.5, HOMA-β(Homeostasis model assessment of islet β cell) =(20×FINS in m IU/L)/(FPG in mmol/L-3.5), ΔINS30/ΔG30(early-phase insulin secretion) =ΔInsulin(30-0min) in m IU/L)/(ΔGlucose(30-0min) in mmol/L).3 Statistical analyses: Data were analyzed using SPSS statistical software version 13.0. Normal distribution data were expressed as means ± SD. Non-normal distribution data were expressed as median(1~3 quartile). Comparison between groups: Data with distribution and homogeneity(α=0.10) were performed by one-way analysis of variance(ANOVA),α=0.05. LSD-t test was used between groups, α =0.017. Data with non-normal distribution were performed with Kruskal-Wallis test, α =0.05. While Mann-Whitney U test was used between groups, α=0.017. The association between serum FGF21 and CRP with other parameters were evaluated by Pearson correlation analysis and Spearman rank correlation analysis. Multiple stepwise regression analysis was carried out for multivariate analysis.Results:1 The level of serum FGF21 was significantly increased in T2 DM group and IGR group compared with NGT group(P=0.000), and there was no significant difference between IGR group and T2 DM group.2 The level of serum CRP was significantly increased in T2 DM group(P=0.000), and there was no significant difference between IGR group and NGT group.3 Significant correlations between FGF-21 and HDL-C, ΔINS30/ΔG30, HOMA-IR(r=-0.265, P<0.05, r=-0.644, P<0.001, r=0.858, P<0.001) were observed. Multiple regression analysis showed that HDL-C was the strongest independent predictor for serum FGF21. YFGF21=455.432-90.239×XHDL-C. Serum CRP was positively correlated with TG, FPG, 2h PG, FINS, HOMA-IR(r=0.315, 0.708, 0.749, 0.477, 0.633, all p < 0.05), and negatively correlated with ΔINS30/ΔG30(r=-0.507, P<0.001). Multiple regression analysis showed that 2h PG was a significantly influential factor for CRP. YCRP=-0.02+0.199×X2h PG.4 Serum FGF21 was positively correlated with CRP(r=0.396, P<0.001).Conclusions:1 Serum FGF21 can be a predicted factor to evaluate the development of type 2 diabetes mellitus.2 Serum FGF21 could play a role to compensate the inflammation state.