成人1型糖尿病胰岛素抵抗与糖尿病肾脏疾病的关联探索

    Association between insulin resistance and diabetic kidney disease among adults with type 1 diabetes

    • 摘要:
      目的  探究胰岛素抵抗(insulin resistance,IR)与糖尿病肾脏疾病(diabetic kidney disease,DKD)在1型糖尿病(type 1 diabetes mellitus,T1DM)中的关联,并在成人T1DM患者中分析对比多个替代指标所反映的IR与DKD的关联。
      方法  本研究为横断面调查研究。选取2008年10月至2021年6月在空军军医大学西京医院住院的556例成人经典T1DM患者为研究对象,收集人口学、身体测量学和实验室指标。计算IR相关指标:估计葡萄糖处置率(estimated glucose disposal rate,eGDR),胰岛素抵抗代谢评分(metabolic score for insulin resistance,METS-IR),三酰甘油葡萄糖指数(triglyceride-glucose index,TyG)。将患者分为DKD组和非DKD组。利用逻辑回归和限制性立方样条(restricted cubic spline,RCS)模型探索IR与DKD的关联,绘制受试者工作特征(receiver operating characteristic,ROC)曲线并比较各指标的识别性能。
      结果  患者年龄31.0(24.8,44.0)岁,病程6.0(2.0,12.0)年,DKD患病率为20.14%。低eGDR与DKD患病相关。矫正多个协变量后,与由体重指数计算的预估葡萄糖处置率(eGDR calculated with body mass index,eGDRBMI)最低四分位Q1相比,位于Q2Q4的患者DKD患病风险OR(95%CI)分别为1.08(0.40~2.92)、0.13(0.03~0.45)和0.26(0.07~0.83);对应由腰臀比计算的预估葡萄糖处置率(eGDR calculated with waist-to-hip ratio,eGDRWHRQ2Q4的风险分别是0.68(0.20~2.23)、0.51(0.15~1.66)、0.16(0.03~0.72)。TyG、由腰围计算的预估葡萄糖处置率(eGDR calculated with waist circumference,eGDRWC)、METS-IR、体重指数、腰高比、腰臀比均与DKD患病无明显关联。亚组分析显示,在女性、年龄28~<40岁、≥40岁、病程≥5年、当前不吸烟、有糖尿病家族史六个亚组中,eGDRBMI与DKD的关联与整体研究患者一致。RCS提示eGDRBMI、eGDRWHR与DKD患病风险呈线性负相关。ROC分析显示,eGDRBMI、eGDRWHR和eGDRWC识别DKD的切点值分别为8.23 mg·kg−1·min−1、7.22 mg·kg−1·min−1和7.92 mg·kg−1·min−1。当添加进入基础模型,三个eGDR指标均可进一步提升模型识别性能。
      结论  在成人T1DM患者中,eGDR降低所反映的IR与DKD患病相关,eGDR在成人T1DM患者DKD的识别中存在一定价值,其临床意义有待在更多研究中进一步证实。

       

      Abstract:
      Objective  To explore the association between insulin resistance (IR) and diabetic kidney disease (DKD) among adults with type 1 diabetes mellitus (T1DM) and compare multiple surrogate parameters of IR for their associations with DKD in this population.
      Methods  For this cross-sectional study, 556 adults with classic T1DM admitted into Xijing Hospital between October 2008 and June 2021 were enrolled. Demographic, anthropometric and laboratory data were collected. IR-related parameters of estimated glucose disposal rate (eGDR), metabolic score for insulin resistance (METS-IR) and triglyceride-glucose index (TyG) were calculated. They were categorized into two groups of DKD and non-DKD. The relationship between IR and DKD was explored by binary Logistic regression and restricted cubic spline (RCS) models. Receiver operating characteristic (ROC) curves were plotted for comparing the discriminatory performance of all parameters.
      Results  Median age was 31.0(24.8, 44.0) year and median disease duration 6.0(2.0, 12.0) year. The prevalence of DKD was 20.14%. Lower eGDR was associated with a high prevalence of DKD. In multivariable analysis, as compared to quartile 1 (Q1), odds ratios (OR, 95%CI) of DKD for participants in eGDR calculated with body mass index (eGDRBMIQ2-Q4 were 1.08(0.40-2.92), 0.13(0.03-0.45) and 0.26(0.07-0.83), respectively. The corresponding risk in eGDR calculated with waist-to-hip ratio (eGDRWHRQ2-Q4 was 0.68(0.20-2.23), 0.51(0.15-1.66) and 0.16(0.03-0.72), respectively. TyG, eGDR calculated with waist circumference (eGDRWC), METS-IR, body mass index, waist-to-height ratio and waist-to-hip ratio were not significantly associated with the prevalence of DKD. Subgroup analyses indicated that the association between eGDRBMI and DKD was consistent with overall population in six subgroups of females, age 28-<40 years and ≥40 years, disease duration ≥5 years, non-smokers and individuals with a family history of diabetes. RCS hinted at a linear and negative correlation between eGDRBMI, eGDRWHR and the prevalence of DKD. ROC analyses indicated that the cutoff values for identifying DKD were 8.23 mg·kg−1·min−1, 7.22 mg·kg−1·min−1 and 7.92 mg·kg−1·min−1 for eGDRBMI, eGDRWHR and eGDRWC, respectively. After adding into a basic model, all three eGDRs demonstrated incremental discriminatory performance.
      Conclusion  IR, reflected by a declining eGDR, is associated with the prevalence of DKD among adults with classic T1DM. And eGDR has demonstrated some potential in identifying DKD in adult classic T1DM and its clinical implication should be validated by more studies.

       

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