Liu Jie, Wang Xu, Gao Tian Ye, Zhang Qing, Zhang Sheng Nan, Xu Yuan Yuan, Yao Wen Qiang, Yang Zhen Hua, Yan Hao Jie
Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
The Third Hospital of Guangxi University of Chinese Medicine, Liuzhou, Guangxi, China.
Front Endocrinol (Lausanne). 2024 Jul 24;15:1362077. doi: 10.3389/fendo.2024.1362077. eCollection 2024.
Erythrocyte dysfunction is a characteristic of diabetes mellitus (DM). However, erythrocyte-associated biomarkers do not adequately explain the high prevalence of DM. Here, we describe red blood cell distribution width to albumin ratio (RAR) as a novel inflammatory biomarker for evaluating an association with DM prevalence and prognosis of all-cause mortality.
Data analyzed in this study were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. A total of 40,558 participants (non-DM and DM) were enrolled in the study; RAR quartiles were calibrated at Q1 [2.02,2.82] mL/g, Q2 (2.82,3.05] mL/g, Q3 (3.05,3.38] mL/g, and Q4 (3.38,12.08] mL/g. A total of 8,482 DM patients were followed (for a median of 84 months), of whom 2,411 died and 6,071 survived. The prevalence and prognosis associated with RAR and DM were analyzed; age and sex were stratified to analyze the prevalence of RAR in DM and the sensitivity of long-term prognosis.
Among non-DM (=30,404) and DM (=10,154) volunteers, DM prevalence in RAR quartiles was 8.23%, 15.20%, 23.92%, and 36.39%. The multivariable odds ratio (OR) was significant for RAR regarding DM, at 1.68 (95% CI 1.42, 1.98). Considering Q1 as a foundation, the Q4 OR was 2.57 (95% CI 2.11, 3.13). The percentages of DM morbidity varied across RAR quartiles for dead (=2,411) and surviving (=6,071) DM patients. Specifically, RAR quartile mortality ratios were 20.31%, 24.24%, 22.65%, and 29.99% (P<0.0001). The multivariable hazard ratio (HR) for RAR was 1.80 (95% CI 1.57, 2.05). Considering Q1 as a foundation, the Q4 HR was 2.59 (95% CI 2.18, 3.09) after adjusting for confounding factors. Sensitivity analysis revealed the HR of male DM patients to be 2.27 (95% CI 1.95, 2.64), higher than females 1.56 (95% CI 1.31, 1.85). DM patients who were 60 years of age or younger had a higher HR of 2.08 (95% CI1.61, 2.70) as compared to those older than 60 years, who had an HR of 1.69 (95% CI 1.47, 1.94). The HR of RAR in DM patients was optimized by a restricted cubic spline (RCS) model; 3.22 was determined to be the inflection point of an inverse L-curve. DM patients with a RAR >3.22 mL/g suffered shorter survival and higher mortality as compared to those with RAR ≤3.22 mL/g. OR and HR RAR values were much higher than those of regular red blood cell distribution width.
The predictive value of RAR is more accurate than that of RDW for projecting DM prevalence, while RAR, a DM risk factor, has long-term prognostic power for the condition. Survival time was found to be reduced as RAR increased for those aged ≤60 years among female DM patients.
红细胞功能障碍是糖尿病（DM）的一个特征。然而，红细胞相关生物标志物并不能充分解释DM的高患病率。在此，我们将红细胞分布宽度与白蛋白比值（RAR）描述为一种新型炎症生物标志物，用于评估其与DM患病率及全因死亡率预后的关联。
本研究分析的数据来自1999 - 2020年美国国家健康与营养检查调查（NHANES）。共有40558名参与者（非DM和DM）纳入研究；RAR四分位数校准为Q1[2.02,2.82]mL/g、Q2(2.82,3.05]mL/g、Q3(3.05,3.38]mL/g和Q4(3.38,12.08]mL/g。共对8482名DM患者进行随访（中位随访84个月），其中2411人死亡，6071人存活。分析了与RAR和DM相关的患病率及预后；按年龄和性别分层分析DM中RAR的患病率及长期预后的敏感性。
在非DM（=30404）和DM（=10154）志愿者中，RAR四分位数组的DM患病率分别为8.23%、15.20%、23.92%和36.39%。RAR关于DM的多变量优势比（OR）显著，为1.68（95%CI 1.42,1.98）。以Q1为基础，Q4的OR为2.57（95%CI 2.11,3.13）。死亡（=2411）和存活（=6071）的DM患者中，DM发病率在RAR四分位数组间有所不同。具体而言，RAR四分位数组的死亡率分别为20.31%、24.24%、22.65%和29.99%（P<0.0001）。RAR的多变量风险比（HR）为1.80（95%CI 1.57,2.05）。以Q1为基础，调整混杂因素后，Q4的HR为2.59（95%CI 2.18,3.09）。敏感性分析显示，男性DM患者的HR为2.27（95%CI 1.95,2.64），高于女性的1.56（95%CI 1.31,1.85）。60岁及以下的DM患者HR为2.08（95%CI1.61,2.70），高于60岁以上患者的1.69（95%CI 1.47,1.94）。通过限制立方样条（RCS）模型优化了DM患者中RAR的HR；确定3.22为反L曲线的拐点。与RAR≤3.22 mL/g的DM患者相比，RAR>3.22 mL/g的DM患者生存期更短，死亡率更高。RAR的OR和HR值远高于常规红细胞分布宽度。
对于预测DM患病率，RAR的预测价值比红细胞分布宽度（RDW）更准确，而RAR作为DM的一个危险因素，对该疾病具有长期预后能力。在年龄≤60岁的女性DM患者中，发现随着RAR升高，生存时间缩短。
