Department of Cardiology, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.167, Beilishi Road, 100037, Xicheng DistrictBeijing, China.
Cardiovasc Diabetol. 2024 Jun 6;23(1):194. doi: 10.1186/s12933-024-02256-5.
Recent studies have suggested that insulin resistance (IR) contributes to the development of cardiovascular diseases (CVD), and the estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker of IR. However, most existing evidence stems from studies involving diabetic patients, potentially overstating the effects of eGDR on CVD. Therefore, the primary objective of this study is to examine the relationship of eGDR with incidence of CVD in non-diabetic participants.
The current analysis included individuals from the China Health and Retirement Longitudinal Study (CHARLS) who were free of CVD and diabetes mellitus but had complete data on eGDR at baseline. The formula for calculating eGDR was as follows: eGDR (mg/kg/min) = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)]. The individuals were categorized into four subgroups according to the quartiles (Q) of eGDR. Crude incidence rate and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to investigate the association between eGDR and incident CVD, with the lowest quartile of eGDR (indicating the highest grade of insulin resistance) serving as the reference. Additionally, the multivariate adjusted restricted cubic spine (RCS) was employed to examine the dose-response relationship.
We included 5512 participants in this study, with a mean age of 58.2 ± 8.8 years, and 54.1% were female. Over a median follow-up duration of 79.4 months, 1213 incident CVD cases, including 927 heart disease and 391 stroke, were recorded. The RCS curves demonstrated a significant and linear relationship between eGDR and all outcomes (all P for non-linearity > 0.05). After multivariate adjustment, the lower eGDR levels were founded to be significantly associated with a higher risk of CVD. Compared with participants with Q1 of eGDR, the HRs (95% CIs) for those with Q2 - 4 were 0.88 (0.76 - 1.02), 0.69 (0.58 - 0.82), and 0.66 (0.56 - 0.79). When assessed as a continuous variable, per 1.0-SD increase in eGDR was associated a 17% (HR: 0.83, 95% CI: 0.78 - 0.89) lower risk of CVD, with the subgroup analyses indicating that smoking status modified the association (P for interaction = 0.012). Moreover, the mediation analysis revealed that obesity partly mediated the association. Additionally, incorporating eGDR into the basic model considerably improve the predictive ability for CVD.
A lower level of eGDR was found to be associated with increased risk of incident CVD among non-diabetic participants. This suggests that eGDR may serve as a promising and preferable predictor and intervention target for CVD.
最近的研究表明，胰岛素抵抗（IR）会导致心血管疾病（CVD）的发生，估计葡萄糖处置率（eGDR）被认为是 IR 的可靠替代标志物。然而，大多数现有证据来自于涉及糖尿病患者的研究，可能夸大了 eGDR 对 CVD 的影响。因此，本研究的主要目的是在非糖尿病患者中研究 eGDR 与 CVD 发生率之间的关系。
本分析纳入了来自中国健康与退休纵向研究（CHARLS）的个体，这些个体无 CVD 和糖尿病，但在基线时有完整的 eGDR 数据。eGDR 的计算公式如下：eGDR（mg/kg/min）=21.158-（0.09×WC）-（3.407×高血压）-（0.551×HbA1c）[WC（cm），高血压（是=1/否=0）和 HbA1c（%）]。根据 eGDR 的四分位数（Q）将个体分为四个亚组。计算粗发病率和危险比（HR）及 95%置信区间（CI），以调查 eGDR 与新发 CVD 之间的关联，将 eGDR 最低四分位数（表示胰岛素抵抗程度最高）作为参考。此外，还采用多元调整限制立方脊柱（RCS）来检查剂量-反应关系。
本研究纳入了 5512 名参与者，平均年龄为 58.2±8.8 岁，54.1%为女性。在中位随访时间为 79.4 个月期间，记录了 1213 例新发 CVD 病例，包括 927 例心脏病和 391 例中风。RCS 曲线显示 eGDR 与所有结局之间存在显著且线性的关系（所有非线性 P 值均>0.05）。经过多变量调整后，发现较低的 eGDR 水平与 CVD 风险增加显著相关。与 eGDR Q1 组相比，eGDR Q2-Q4 组的 HR（95%CI）分别为 0.88（0.76-1.02）、0.69（0.58-0.82）和 0.66（0.56-0.79）。当作为连续变量评估时，eGDR 每增加 1.0-SD，CVD 风险降低 17%（HR：0.83，95%CI：0.78-0.89），亚组分析表明吸烟状况改变了这种关联（交互作用 P 值=0.012）。此外，中介分析显示肥胖部分介导了这种关联。此外，将 eGDR 纳入基本模型可显著提高 CVD 的预测能力。
在非糖尿病患者中，较低的 eGDR 水平与新发 CVD 风险增加相关。这表明 eGDR 可能是 CVD 的一个有前途和理想的预测指标和干预靶点。
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