The Associations Of Serum Levels Of Irisin And FGF21 With Body Composition And Bone Mineral Density In Postmenopausal Women With Type 2 Diabetes Mellitus

ObjectiveTo investigate the associations of circulating levels of irisin and fibroblast growth factor 21(FGF21)with the body composition and bone mineral density(BMD)in postmenopausal women with T2DM.A total of 383 postmenopausal women were recruited in the cross-sectional study,including 250 subjects with T2DM and 133 subjects with non-T2DM.All participants received questionnaire survey,physical examination,metabolic parameters and serum irisin and FGF21 levels measurement.In addition,the body composition and BMD were measured by dual energy X-ray absorptiometry(DXA)and the 10-year probability of a major osteoporotic fracture were evaluated by FRAX(fracture risk assessment tool).According to diagnostic criteria of Asian working group on sarcopenia(AWGS),postmenopausal women with T2DM were stratified into sarcopenia subgroup and non-sarcopenia subgroup;according to standard of obesity(Deurenberg et al,Korea),postmenopausal women with T2DM were divided into obesity subgroup and non-obesity subgroup;on the basis of World Health Organization(WHO)diagnostic criteria of osteoporosis,postmenopausal women with T2DM were classified into three subgroups:normal subgroup,osteopenia subgroup,osteoporosis subgroup.The data were analyzed by using two independent sample t-test,Mann-Whitney U test,variance analysis,Chi-square test,Pearson correlation analysis and multivariate linear regression analysis.Results1.Comparison between T2DM group and non-T2DM group in postmenopausal women Compared with non-T2DM group,T2DM group had higher mean levels of waist circumference(WC),detection rate of sarcopenia,detection rate of obesity,detection rate of osteoporosis,total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),hemoglobin Alc(HbAlc),fasting blood glucose(FBG).visceral adipose tissue mass(VAT-M).visceral adipose tissue volume(VAT-V),visceral adipose tissue area(VAT-A),percentage of Android fat(PAF)/percentage of Gynoid fat(PGF),10-year probability of a major osteoporotic fracture with BMD(PMOF),10-year probability of hip fracture with BMD(PHF).On the contrary,T2DM subjects had lower levels of handgrip strength,PGF,bone mineral content(BMC),femoral neck and forearm BMD,serum irisin and FGF21.2.Comparison between sarcopenia subgroup and non-sarcopenia subgroup in postmenopausal women with T2DM Body weight,body mass index(BMI),WC,handgrip strength,TG,FBG,fasting C-peptide(F-CP),fat mass,fat mass index(FMI),VAT-M,VAT-V,VAT-A,PAF,PAF/PGF,muscle mass,percentage of muscle mass,skeletal muscle mass index(SMI),BMC,lumbar spine,femoral neck,total hip,forearm and total body BMD and serum irisin were significantly decreased in sarcopenia subgroup.But PMOF and PHF were higher in sarcopenia subgroup than that in non-sarcopenia subgroup.3.Comparison between obesity subgroup and non-obesity subgroup in postmenopausal women with T2DM In contrast with non-obesity subgroup,obesity subgroup was more likely to have higher levels of body weight,BMI,WC,TQ LDL-C,fat mass,percentage of fat mass,FMI,VAT-M,VAT-V,VAT-A.PAF,PGF and serum irisin.High-density lipoprotein cholesterol(HDL-C),percentage of muscle mass were lower in obesity subgroup.4.Comparison among the three subgroup(normal subgroup,osteopenia subgroup,osteoporosis subgroup)in postmenopausal women with T2DM Among the three subgroup,age,PMOF and PHF tended to be increased,and body weight,WC,handgrip strength,muscle mass,SMI,BMC,lumbar spine,femoral neck,total hip,forearm and total body BMD tended to be decreased.Menopause age,BMI,?-cell function(Homa-?),fat mass,and FMI were higher in normal subgroup and osteopenia subgroup than osteoporosis subgroup.Normal subgroup had higher TG,LDL-C,and serum irisin than osteopenia subgroup,and had higher VAT-M,VAT-V,VAT-A,PGF and serum irisin than osteoporosis subgroup.5.Correlation analysis of metabolic parameters with muscle mass and fat mass in postmenopausal women with T2DM Pearson correlation analysis showed that muscle mass was positively correlated with body weight,BMI,WC,handgrip strength,TG,Homa-?,fat mass,FMI,VAT-M,VAT-V,VAT-A,SMI,BMC,lumbar spine,femoral neck,total hip,forearm and total body BMD and serum irisin,and negatively correlated with age,PMOF and PHF.Fat mass was positively correlated with body weight,BMI,WC,LDL-C,Homa-?,2h C-peptide(2h-CP),percentage of fat mass,FMI,VAT-M,VAT-V,VAT-A,PAF,PGF,muscle mass,SMI,BMC,lumbar spine,femoral neck,total hip,forearm and total body BMD and serum irisin,and negatively correlated with HDL-C,percentage of muscle mass,PMOF and PHF.6.Multiple linear regression analysis of muscle mass and fat mass with BMD in postmenopausal women with T2DM Multiple linear regression analysis in which muscle mass was as dependent variable indicated that muscle mass was not associated with lumbar spine,femoral neck,total hip,forearm and total body BMD after adjustment for body weight.Multiple linear regression analysis in which fat mass was as dependent variable indicated that fat mass was not associated with lumbar spine,femoral neck,total hip,forearm and total body BMD after adjustment for body weight.7.Correlation analysis of metabolic parameters with serum irisin and FGF21 in postmenopausal women with T2DM Pearson correlation analysis revealed that circulating irisin was significantly positively correlated with body weight,BMI,WC,TG,fat mass,muscle mass,SMI,femoral neck,total hip,forearm and total body BMD.Serum FGF21 concentrations were negatively correlately with total cholesterol(TC),LDL-C and FBG,and positively correlated with insulin sensitivity(Homa-S).8.Association of serum irisin with body composition and BMD in postmenopausal women with T2DM in multiple linear regression model.Multiple linear regression model showed that there was a significant and positive correlation between serum irisin and age,BMI,muscle mass and femoral neck BMD.Conclusions1.In postmenopausal women,serum irisin and FGF21 in T2DM group were lower than non-T2DM group.2.In postmenopausal women with T2DM,serum irisin was positively correlated with TG.Serum FGF21 was negatively correlated with TC?LDL-C?FBG,and positively correlated with Homa-S.3.In postmenopausal women with T2DM,serum irisin in postmenopausal women with T2DM was positively associated with muscle mass,fat mass and femoral neck,total hip,forearm and total body BMD.Irisin is expected be a novel drug to improve glucose,lipids and bone metabolism.However,there were no correlations between serum FGF21 and muscle mass,fat mass and BMD.The mechanisms need to be further explored.