Reciprocal Relations Of Visceral Fat To Bone Mineral Density In Patients With Type2Diabetes Mellitus

Objective: Type2diabetes mellitus (T2DM) is a disorder thatmetabolically is characterized by changes not only in carbohydrate, lipid andprotein but also in bone. What,s more, patients with T2DM tend to be withabdominal obesity. A consistent body of literature suggests that, the pattern ofregional fat deposition, composed of subcutaneous adipose tissue (SAT) andvisceral adipose tissue (VAT), tends to be a stronger predictor of disease risk,as compared with overall fat mass. However, it is still unknown that whetherthe fat-bone link is related to differences in fat distribution. Quantitativeanalysis of computed tomography(CT), which can distinguish VAT from SAT,is the gold standard for assessing the distribution of visceral fat currently. Inthe circulation, retinol-binding protein4(RBP4), which is secreted byadipocytes and the liver tissue, is the transport protein for retinol. Recently, ithas been implicated as a key factor in insulin resistance and obesity. Thus,excessive vitamin A intake for a long time may undermine bone health. Theobjective of this research is to investigate the association between the patternof regional fat deposition, especially VAT, and bone mineral density (BMD)in male and postmenopausal patients with T2DM and whether RBP4is relatedto BMD in patients.Methods: The cross-sectional study involved98patients,who wererandomly sampled from the department of endocrinology of the ThirdHospital affiliated to Hebei Medical University. The sample includes57postmenopausal female T2DM patients, mean age61years (40~73years) andmedian of postmenopausal time8years, and41male T2DM patients, meanage55years (37~76years).Clinical data were asked in detail. Body weightand height were measured and body mass index (BMI) was calculated. Fasting plasma glucose (FPG), fasting insulin (FINS) and glycosylated hemoglobinA1c (HbA1c) were measured. Serum RBP4concentration was determined byenzyme-linked immuno sorbent assay (ELISA). Insulin resistance index wasassessed by homeostasis model (HOMA-IR)(formula,HOMA-IR=FPG×FINS/22.5). CT were performed in the fasting statemeasuring SAT and VAT of umbilical plane. BMD determined at the lumbarspine (L2-4), femoral neck, greater trochanter and intertrochanter site wasassessed using dual emission X-ray absorptiometry (DEXA, France,MEDILINK, Osteocore III). The postmenopausal T2DM patients weredivided into four groups in according to the mean of BMI and the mean ofVAT(group1, BMI＜26.04kg/m~2and VAT＜155.31cm~2; group2, BMI＜26.04kg/m~2and VAT＞155.31cm~2; group3, BMI＞26.04kg/m~2and VAT＜155.31cm~2; group4, BMI＞26.04kg/m~2and VAT＞155.31cm~2). The malepatients with T2DM were divided into group A(VS＜0.66) and group B(VS＞0.66)on the basis of the mean of the ratio of VAT to SAT.Statistical analysis: SPSS13.0software was used for statistical analyses.Quantitative data meeting normal distribution were summarized using Meanand SD, while quantitative data not meeting normal distribution weresummarized either using median and quartile range or using Mean and SD,after natural logarithm-transformation.The comparisons of mean differencesof multiple group measurement data were made by analysis of variance(ANOVA), and the multiple comparisons were made by least significantdifference (LSD). The comparisons of mean differences were made bytwo-sample t-test. Pearson correlations were used to examine associationsbetween clinical variables and BMD in male group and female group,respectively. Model multiple regression fit by enter method to determine theinfluence of VAT on bone phenotypes. A value of p＜0.05(at two-sided) wasconsidered statistically significant.Results:1the results of statistical analysis for postmenopausal female T2DMpatients 1.1A simple correlation analysis revealed that Weight,BMI and FINSwere significantly and positively correlated to LS-BMD,FN-BMD,IT-BMD,and GT-BMD. Age and the postmenopausal time (PMT) were negativelyrelated to BMD at any site measured.LNRBP4was only negatively related toLS-BMD(r=-0.295)b ut not to other sites.(p＜0.05).1.2VAT showed associations with Age,HOMA-IR,LNRBP4and SATsignificantly in postmenopausal female T2DM patients.(p values were0.034,0.003,0.000,0.020, respectively.)Moreover,VAT was significantlyand negatively related to LS-BMD (r=-0.367) and GT-BMD(r=-0.301), andshowed negative associations with BMD at any site measured even afteradjusting for BMI, SAT,LNRBP4and HOMA-IR.(p＜0.05)1.3The postmenopausal female patients with T2DM were divided intofour groups in according to the mean of BMI and the mean of VAT. TheBMD at any site measured of group3was significantly higher than group2.The GT-BMD and IT-BMD of group3were significantly higher than group1.The LS-BMD of group1was significantly higher than group2.(p＜0.05)1.4The multiple regression fit, modeling by enter method, indicated thatthe variation of the predictors (Age, DUR, BMI, VAT, HbA1c, FINS andPMT)explained51.7%,52.2%,59.8%, and75.3%of the variation inLS-BMD,FN-BMD,IT-BMD,GT-BMD between subjects, respectively.(p＜0.01)2the results of statistical analysis for male T2DM patients2.1A simple correlation analysis revealed that FINS was significantlyand positively correlated to GT-BMD in male patients with T2DM(r=0.445,p＜0.05).2.2VAT of male T2DM patients showed a positive association withHOMA-IR(r=0.343, p=0.024)2.3VAT was significantly and negatively related to FN-BMD (r=-0.445)and GT-BMD(r=-0.403), and showed more negative associations afteradjusting for BMI, SAT, LNRBP4and HOMA-IR.(p＜0.05)2.4The male patients with T2DM were divided into two groups on the basis of the mean of the ratio of VAT to SAT. The LS-BMD, FN-BMD andGT-BMD of group B were significantly lower than group A.(p＜0.05)2.5The multiple regression fit, modeled by enter method, indicated thatthe variation of the predictors (Age, DUR, BMI, VAT, HbA1c and FINS)explained20.6%and26.7%of the variation in FN-BMD and GT-BMDbetween subjects, respectively.(p＜0.05)Conclusions:1The influence of adipose tissue on bone metabolism in T2DM patientsmay depend on the pattern of regional fat deposition. Serum RBP4may playan influence in forming BMD.2VAT could be an independent risk factor of BMD in thepostmenopausal female T2DM patients and FN-BMD and GT-BMD in themale T2DM patients.