儿童血清FGF21水平与代谢综合征关系的初步研究

【作者】 王俏镟；

【导师】 向红丁； 黎明；

【作者基本信息】 北京协和医学院 ， 临床医学， 2012， 博士

【摘要】 目的：近年来,由于成纤维细胞生长因子21(FGF21)在动物模型中改善糖脂代谢的良好效果,人们将其作为治疗2型糖尿病的潜在药物寄予厚望。然而,FGF21在人体中的病理生理作用尚不明确,部分研究显示在肥胖、2型糖尿病患者体内FGF21的水平增高,提示存在FGF21抵抗。本研究利用大样本学龄儿童资料,观察血清FGF21水平在儿童的分布及其影响因素,探讨FGF21与儿童期肥胖及代谢综合征(MS)的关系。方法：对来自2004年“北京儿童青少年代谢综合征研究”中整群抽样获得的景山学校820名6-18岁学龄儿童,进行体量指标、Tanner分期、空腹血脂谱、空腹血糖、以及血清胰岛素、瘦素、脂联素、抵抗素和FGF21水平测定。FGF21采用双抗体夹心放大酶联免疫法检测；儿童MS采用改良的美国国家胆固醇计划成人治疗小组第3次报告(ATPⅢ)中的定义进行诊断。结果：1.血清FGF21水平在两性无显著性差异(P=0.082)。青春发育中期两性FGF21水平均有增加趋势。正常体重、超重和肥胖组儿童FGF21水平逐步升高,但无统计学意义。MS组与非MS组,具有MS组分或不具该组分组FGF21水平无显著性差异。2.全体对象中,FGF21与腰围、体重指数(BMI)、体脂含量、收缩压(SBP)、舒张压(DBP)、空腹血糖、胰岛素、血脂谱、瘦素、脂联素、抵抗素的双变量分析显示,FGF21仅与舒张压(r=0.08,P=0,023)、瘦素(1=0.085,P=0.015)及抵抗素(r=0.078,P=0.027)具有相关性,调整年龄、性别、BMI后,空腹血糖亦与FGF21显著相关(r=0.074,P=0.038)。3.将全体儿童按FGF21四分位数分组,可以看到各分组中肥胖儿童比例一致。儿童MS.MS各组分的发生率均表现为FGF21第1分位组较高,第2、第3分位较低,第4分位再度增高的J型曲线。全体对象中MS组分≥1个的比例组间比较具有统计学差异(P=0.016),肥胖儿童中MS发生比例亦具有统计学差异(P=0.044)。女孩中低脂联素血症的发生率随FGF21四分位变化亦表现为上述J型曲线。4.logistic回归显示,全体儿童中FGF21水平的升高(OR=I.681,P=0.041)或者降低(OR=I.924,P=0.009)均与儿童携带MS组分的风险增加显著相关,肥胖儿童中FGF21的升高与儿童罹患MS风险的增加显著相关(OR=19.971,P=0.013),且这种风险度的增加独立于儿童的年龄、性别和BMI。结论：儿童人群中FGF21水平与肥胖无显著相关性。儿童人群中存在FGF21相对缺乏和FGF21抵抗两种状态。过低或过高的FGF21水平均与儿童不良代谢状况相关,提示全体儿童携带MS组分以及肥胖儿童罹患MS风险的增加。更多还原

【Abstract】 Objective:Recently, a novel protein, fibroblast growth factor21(FGF21) has gained a lot of attention due to its beneficial effects on glucose homeostasis and lipid metabolism in animal models. However, the physiological and pathologic roles of FGF21in human remain unclear. This study aimed to investigate the relationship between its serum levels and metabolic syndrome (MS) in children.Methods:820Chinese subjects aged6to18years were recruited from the Beijing Child and Adolescent Metabolic Syndrome study. Anthropometric parameters, fasting lipid profile, glucose, fasting insulin, leptin, adiponectin, resistin and FGF21were measured. MS was diagnosed according to the modified Adult Treatment Panel Ⅲ (ATPⅢ) criteria.Results:There was no sex difference in serum FGF21levels (P=0.082). A slightly increase in FGF21levels during middle puberty was observed in both genders.Though medians of FGF21levels in each group increased progressively from normal weight to overweight to obese, they did not reach statistical significant. FGF21levels in children with and without MS did not show significant difference either.In the whole cohort, univariate association analysis between FGF21and waist circumference, body mass index (BMI), fat mass percentage, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose, insulin and fasting lipid profile showed that FGF21only had correlation with DBP (r=0.08, P=0.023), leptin (r=0.085, P=0.015) and resistin (r=0.078, P=0.027). Adjusted for age, gender and BMI, fasting blood glucose also correlated with FGF21(r=0.074, P=0.038)The whole population was then divided into quartiles based on FGF21levels. The percentages of obese children in each group were almost the same. A J-shaped association of the incidences of MS and MS components with FGF21was observed. Both the first and the fouth quartiles were associated with higher incidences of carrying1or more MS components (P=0.016). MS incidences in groups of obese children divided according to the above quartiles also showed significant difference (P=0.044). A J-shaped association of hypoadiponectinemia with FGF21was also observed, but only in girls. In the whole population, logistic regression analysis showed that both high (OR=1.681,P=0.041) and low(OR=1.924,P=0.009) levels of FGF21were associated with increased risk of carrying metabolic components in children, while in the obese subgroup, high level of FGF21was associated with increased risk of developing MS (OR=19.971, P=0.013),even after ajusting for age, gender and BMI.Conclusion:In this study, serum FGF21level did not correlate with obesity. A J-shaped association between FGF21levels and incidences of MS and MS components in children was observed, showing that not only higher level but also lower level of FGF21indicated adverse metabolic profiles.更多还原