Study Of Biomarkers Of Diabetic Peripheral Neuropathy And Macrovascular Disease

Background Fibroblast growth factor 21(FGF21)is an emerging metabolic regulator associated with glucose and lipid metabolism.Ficolin-3,a soluble molecule of the innate system,has a primary role in the activation of the lectin pathway in the complement system.Here,we conducted this study to explore the potential link between FGF21 and lower extremity atherosclerotic disease(LEAD)and the link between serum ficolin-3 and diabetic peripheral neuropathy(DPN)in type 2 diabetic patients,further we explored whether metformin would influence the increased level of FGF21.Methods A cross-sectional study was conducted on about 500 type 2 diabetic patients from Shanghai Jiao-tong University Affiliated Sixth People's Hospital.LEAD was defined by Ankle-brachial index?0.9 and lower extremity arterial plaque evaluated by color Doppler ultrasound.DPN was evaluated by neurological symptoms,neurological signs,neurothesiometer and electromyogram.Serum FGF21 and ficolin-3concentrations were quantified by a sandwich enzyme-linked immunosorbent assay.Statistical analysis was performed to explore the association between serum FGF21 with LEAD,and serum ficolin-3 with DPN.Results1.Serum FGF21 levels in LEAD group were significantly higher than non-LEAD group in females [385.34(243.89-661.54)vs 313.13(156.38-485.79),P=0.006],while not in male patients [295.52(177.09-549.64)vs 342.09(198.70-549.87),P=0.613].In diabetic women,subjects with LEAD had significantly higher serum FGF21 regardless of non-alcoholic fatty liver disease(NAFLD)(P<0.05).After adjusted for other LEAD risk factors,FGF21 was demonstrated to be an independent risk factor for LEAD in type 2 diabetic women(OR,1.106;95%CI 1.008-1.223;P=0.028).Moreover,FGF21 was independently tied to femoral intima-media thickness(?=0.208,P=0.031).In addition,FGF21 was negatively correlated with estradiol in premenopausal diabetic women(r=-0.368,P=0.009).2.In diabetic men,the serum FGF21 level in the metformin group was significantly lower than that in the non-metformin group [303.11(182.9-451.12)vs.342.82(206.93-593.46)ng/ml,P=0.003].The multiple stepwise regression analysis showed that the metformin treatment and triglyceride were the independent risk factors influencing serum FGF21 level in type 2 diabetic men(P<0.05).3.The concentration of serum ficolin-3 was lower in DPN patients compared with non-DPN patients(18.73±4.75 vs.26.69±5.68 ng/mL,P<0.001).In addition,it was found negatively correlated to the vibration perception threshold(r=-0.158,P=0.025).The results of multiple regression analysis of DPN indicated that age,diabetes duration,serum ficolin-3 were independent impact factors for DPN,respectively(P<0.05).Patients were then assigned into quartiles according to the serum ficolin-3levels,and the prevalence of DPN ascend with the concentration of ficolin-3descending(Trend analysis,P<0.001).Compared with ficolin-3 Quartile 1(referent),the risk of DPN was significantly greater in Quartile 2(OR=2.76;95%CI,1.56-4.88;P<0.001),Quartile 3(OR=3.02;95%CI,1.69-5.40;P<0.001)and Quartile 4(OR=6.84;95%CI,3.39-13.80;P<0.001).Conclusions Serum FGF21 level independently and positively links LEAD in Chinese women with type 2 diabetes.The gender difference may be due to different estrogen levels.Metformin attenuate the increase in plasma FGF21 concentrations in male type 2diabetes independently of glycemic effects.Lowe ficolin-3 levelsare independently associated with DPN,and it may be a potential biomarker for DPN.