妊娠期糖尿病史与生物节律紊乱对产后心血管代谢指标的联合作用

Combined effects of prior gestational diabetes history and biorhythm disturbances on postpartum cardiovascular metabolic indicators

目的探讨生物节律紊乱对女性心血管代谢指标的单独作用及其与妊娠期糖尿病(GDM)史的联合作用。方法本研究为队列研究,并依托马鞍山优生优育队列(MABC)。MABC为自2013年5月至2014年9月在马鞍山妇幼保健院建立的出生队列,在妊娠24~28周时进行75 g口服葡萄糖耐量试验以诊断GDM。对来自MABC的女性,采用随机数字表法按照1∶2的比例选取有GDM病史的女性120例,无GDM病史的女性240名,于2021年7月至2022年8月进行随访。最终共纳入符合纳入排除标准的研究对象307例,其中有GDM病史女性99例,无GDM病史女性208例。在随访时,收集研究对象的基本信息,包括年龄、体重指数(BMI)、文化程度、工作性质、婚姻状态、税后总收入、饮酒情况、吸烟情况、不良孕产史、妊娠高血压病史、糖尿病家族史、心血管疾病家族史等,并采集空腹血样检测以下生化指标:空腹血糖(FPG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)、总胆固醇(TC)、尿酸和肌酐等。采用神经精神病学评估生物节律访谈问卷调查研究对象的生物节律并计算得分,选取生物节律得分中位数作为截断值,小于中位数表示生物节律紊乱程度较低,反之生物节律紊乱程度较高。采用线性回归分析法分析生物节律紊乱与心血管代谢指标的关联以及其与GDM病史对心血管代谢指标的联合作用,采用线性模型分析GDM病史和生物节律对于女性产后代谢指标的相加交互作用,使用Benjaminiand Hochberg方法对多重检验P值进行校正,以控制错误发现率(FDR),当调整后的PFDR值<0.05认为有统计学意义。结果线性回归分析结果显示,在调整年龄、BMI、文化程度、工作性质、婚姻状态、税后总收入、饮酒情况、吸烟情况、不良孕产史、GDM病史、妊娠高血压病史、糖尿病家族史、心血管疾病家族史后,与生物节律紊乱程度较低的女性相比,紊乱程度高会增加其HbA1c水平(β=0.08,95%CI 0.02~0.14,P=0.01),但FDR校正后无统计学意义(PFDR=0.13);与无GDM病史且生物节律紊乱程度低的女性相比,生物节律紊乱程度高且有GDM病史的女性FPG(β=0.91,95%CI 0.50~1.31,PFDR=0.001)、HbA1c(β=5.26,95%CI 2.70~7.83,PFDR=0.001)水平显著升高。交互作用分析显示,GDM病史与生物节律紊乱对FPG(P交互=0.03)、HbA1c(P交互=0.03)水平的影响存在相加交互作用。结论有GDM病史且生物节律紊乱程度较高的女性,其FPG、HbA1c的水平会显著增高,提示有GDM病史的女性维持健康的生物节律对心血管健康具有重要作用。

Objective To investigate the sole effect of biorhythm disturbances and its combined effect with a history of gestational diabetes mellitus(GDM)on postpartum cardiovascular metabolic indicators.Methods This was a cohort study based on the Ma′anshan birth cohort(MABC),a birth cohort established at Ma′anshan Maternal and Child Health Care Center from May 2013 to September 2014,where a 75 g oral glucose tolerance test was performed at 24—28 weeks of gestation to diagnose GDM.A total of 120 women and 240 women with and without a history of GDM were selected using the random number table method in a ratio of 1∶2.The participants were followed up from July 2021 to August 2022,and 307 study participants were eventually included in this study,including 99 women with a history of GDM and 208 women without a history of GDM.At the time of follow-up,basic information about the women was collected,including age,body mass index(BMI),education,job nature,marital status,gross after-tax income,alcohol consumption,smoking status,adverse pregnancy and childbirth history,gestational hypertension history,family history of diabetes,family history of cardiovascular disease,etc.Fasting blood samples were collected for measurement of the following biochemical indices:fasting plasma glucose(FPG),glycated hemoglobin A1c(HbA1c),triglycerides(TG),total cholesterol(TC),uric acid and creatinine.The Neuropsychiatric Assessment of Biorhythms Interview Questionnaire was used to assess the biorhythms of the study participants and scores were calculated using the median biorhythm score as the cut-off value,with less than the median indicating low level of biorhythm disturbance,and vice versa for high levels of biorhythm disturbance.Linear regression was used to analyze the associations between biorhythm disturbances and cardiovascular metabolic markers and their combined effect with a history of GDM on cardiovascular metabolic markers,Linear model was used to analyze the summation interaction of GDM history and biorhythms on metabolic indexes in the postpartum period,and P values were corrected for multiple tests using the Benjaminiand Hochberg method to control for the false discovery rate(FDR)and were considered to be statistically significant if the adjusted PFDR value<0.05.Results Linear regression results showed that after adjusting for age,BMI,education,job nature,marital status,gross after-tax income,alcohol consumption,smoking status,adverse pregnancy and childbirth history,GDM,gestational hypertension,family history of diabetes,family history of cardiovascular disease,the degree of biorhythm disturbances was positively associated with the level of glycated haemoglobin(β=0.08,95%CI 0.02-0.14,P=0.01),however,the FDR correction was not statistically significant(PFDR=0.13);compared with women with no history of GDM and a low degree of biorhythm disturbances,women with a prior GDM history and a high degree of biorhythm disturbances had a higher level of FPG(β=0.91,95%CI 0.50-1.31,PFDR=0.001)and a higher level of HbA1c(β=5.26,95%CI 2.70-7.83,PFDR=0.001).Interaction analysis showed that history of GDM and biorhythm disturbances had additive interaction on FPG(PInteraction=0.03),and HbA1c(PInteraction=0.03).Conclusion Our study showed that women with a history of GDM and a high degree of biorhythm disturbance had significantly higher levels of FPG and HbA1c,highlighting the importance of maintaining a healthy biorhythm in women with a prior GDM history.