2型糖尿病患者体重变异性与糖尿病肾病发病风险的相关性

Correlation between weight variability and the risk of diabetic nephropathy in patients with type 2 diabetes mellitus

目的探讨2型糖尿病(T2DM)患者不同体重变异性指标与糖尿病肾病(DKD)发病风险的关系。方法回顾性队列研究。回顾性分析2002—2018年在中国台湾李氏联合诊所进行个案管理的2180例无DKD的T2DM患者的临床资料,女1103例,男1077例,年龄(64.8±12.4)岁。对患者进行定期随访,至少2年,每年监测其代谢指标,依据患者每年记录的体质指数(BMI)计算其独立于均值的变异性(BMI-VIM)、平均真实变异性(BMI-ASV)、变异系数(BMI-CV)和标准差(BMI-SD)。根据4种体重变异性指标的四分位数,分别将患者分为Q_(1)、Q_(2)、Q_(3)、Q_(4)四组。根据随访结束时是否发生DKD将患者分为DKD组和无DKD组(NDKD组)。采用Cox比例风险回归模型分析4种体重变异性指标与DKD发病风险的关系,再以BMI<28 kg/m^(2)为非肥胖组,BMI≥28 kg/m^(2)为肥胖组进行亚组分析,探讨4项体重变异性指标对DKD发病风险的影响。结果所有患者经过(4.55±2.13)年随访后,904例患者发生DKD。与NDKD组相比,DKD组患者女性较多、年龄较大、糖尿病病程更长、使用胰岛素的比例更高、腰臀比更大,BMI-VIM、BMI-ASV、BMI-CV、BMI-SD、收缩压、舒张压、尿白蛋白/肌酐比值均较高,服用降糖药的比例、估算的肾小球滤过率、高密度脂蛋白胆固醇水平均较低,两组差异均有统计学意义(均P<0.05)。Cox比例风险回归结果显示,在校正系列影响因素后,T2DM患者发生DKD的风险随着BMI-SD、BMI-CV、BMI-VIM和BMI-ASV的增加而增加。在BMI-VIM分组中,与Q_(1)组相比,Q_(4)组发生DKD的风险增加22.4%[HR=1.224(95%CI:1.008~1.487),P=0.041];在BMI-ASV分组中,与Q_(1)组相比,Q_(4)组发生DKD的风险增加51.1%[HR=1.511(95%CI:1.240~1.841),P<0.01];在BMI-CV分组中,与Q_(1)组相比,Q_(4)组发生DKD的风险增加22.2%[HR=1.222(95%CI:1.006~1.485),P=0.044];在BMI-SD分组中,与Q_(1)组相比,Q_(4)组发生DKD的风险增加22.2%[HR=1.222(95%CI:1.002~1.490),P=0.048]。亚组分析显示,非肥胖组中以BMI-ASV分组时,在校正系列影响因素后,与Q_(1)组相比,Q_(4)组发生DKD风险最高[HR=1.551(95%CI:1.228~1.958),P<0.001];肥胖组中以BMI-ASV分组时,在校正系列影响因素后,与Q_(1)组相比,Q_(4)组发生DKD风险最高[HR=1.703(95%CI:1.168~2.485),P=0.006]。结论BMI-VIM、BMI-ASV、BMI-CV、BMI-SD的升高会使T2DM患者发生DKD的风险增加。

Objective To evaluate the relationship between different indexes of weight variability and the risk of diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods A retrospective cohort study.The clinical data of 2180 T2DM patients without DKD who underwent case management at Lee′s United Clinic in Taiwan,China from^(2)002 to 2018 were retrospectively analyzed,including 1103 females and 1077 males,with an average age of(64.8±12.4)years.Regular follow-up was conducted for patients for at least 2 years,and their metabolic indexes were monitored annually.BMI variability independent of the mean(BMI-VIM),average yearly mean square successive difference(BMI-ASV),coefficient of variation(BMI-CV)and standard deviation(BMI-SD)were calculated,based on the body mass index(BMI)recorded annually by the patients.Patients were divided into four groups(Q_(1)-Q_(4))based on the quartiles of the four weight variability indexes.DKD group and non-DKN group(NDKD group)were defined based on the occurrence of DKD at the end of the follow-up.Cox proportional hazards regression models were used to analyze the relationship between the four weight variability indicators and the incidence of DKD.Subgroup analysis was performed by categorizing patients into non-obesity(BMI<28 kg/m^(2))and obesity groups(BMI≥28 kg/m^(2))to investigate the impact of the four weight variability indicators on the risk of DKD.Results After a follow-up of(4.55±2.13)years,904 patients developed DKD.Compared with the NDKD group,patients in the DKD group had a higher proportion of females,older age,longer duration of diabetes,more insulin users,higher waist-to-hip ratio,higher levels of BMI-VIM,BMI-ASV,BMI-CV,BMI-SD,systolic blood pressure,diastolic blood pressure,and urine albumin-creatinine ratio,a lower proportion of hypoglycemic drugs,estimated glomerular filtration rate,and high-density lipoprotein cholesterol level,with statistically significant differences between the two groups(all P<0.05).Cox proportional hazards regression analysis results revealed that the risk of DKD in T2DM patients increased with the increase in BMI-SD,BMI-CV,BMI-VIM,and BMI-ASV after correcting a series of influencing factors.In the BMI-VIM subgroup,compared with the Q_(1)group,the risk of DKD in the Q_(4)group increased by 22.4%[HR=1.224(95%CI:1.008-1.487),P=0.041].In the BMI-ASV group,compared with the Q_(1)group,the risk of DKD in the Q_(4)group increased by 51.1%[HR=1.511(95%CI:1.240-1.841),P<0.01].In the BMI-CV group,compared with the Q_(1)group,the risk of DKD in the Q_(4)group increased by 22.2%[HR=1.222(95%CI:1.006-1.485),P=0.044].In the BMI-SD subgroup,compared with the Q_(1)group,the risk of DKD in the Q_(4)group increased by 22.2%[HR=1.222(95%CI:1.002-1.490),P=0.048].Sub-group analysis showed that when the non-obesity group was grouped by BMI-ASV,after correcting a series of influencing factors,compared with the Q_(1)group,the highest risk of DKD occurred in the Q_(4)group[HR=1.551(95%CI:1.228-1.958),P<0.001];when the obesity group was grouped by BMI-ASV,after correcting a series of influencing factors,compared with the Q_(1)group,the highest risk of DKD occurred in the Q_(4)group[HR=1.703(95%CI:1.168-2.485),P=0.006].Conclusion Increases in BMI-VIM,BMI-ASV,BMI-CV,and BMI-SD are associated with an increased risk of DKD in T2DM patients.