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ARTICLE  文章

Imaging-based body fat distribution and diabetic retinopathy in general US population with diabetes: an NHANES analysis (2003-2006 and 2011-2018)
美国普通糖尿病患者基于成像的体脂分布与糖尿病视网膜病变：NHANES 分析（2003-2006 年和 2011-2018 年）

Chenxin Li , Yili Zhang , Yujie Wang , Chufeng , Mingming , Xiaoyin , Yongdong Chen andZhi Zheng 凶The Author(s) 2024 作者 2024

Abstract 摘要

BACKGROUND: Limited studies have investigated the correlation between fat distribution and the risk of diabetic retinopathy (DR) in the general population with diabetes. The relationship between obesity and DR remains inconclusive, possibly due to using simple anthropometric measures to define obesity. This study investigates the relationships between the android-to-gynoid fat ratio (A/G ratio, measured using dual-energy X-ray absorptiometry) and DR within the US population with diabetes. METHODS: The study used a population-based, cross-sectional approach based on the 2003-2006 and 2011-2018 data of the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression analyses were performed on participants with diabetes to evaluate the contribution of body mass index (BMI), waist-to-height ratio (WHtR), and A/G ratio to the prevalence of DR. RESULTS: The prevalence of DR was , and among participants with ratios , and , respectively. After adjusting sex, age, ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, and non-high-density lipoprotein cholesterol level, a higher A/G ratio ( ) was independently associated with decreased odds of DR (odds ratio [OR], : ) compared with the A/G ratio of 1.0-1.2. Associations between a higher A/G ratio and DR remained statistically significant after adjusting for BMI (OR, Cl: ) and WHtR (OR, ). Moreover, these associations remained statistically significant in analyses using the ethnic-specific tertiles for the A/G ratio. In sex-stratified models, these correlations remained in males. There was a significant inverse association between the A/G ratio and diabetes duration in males, which persisted after multivariable adjustments ( ). CONCLUSIONS: A novel finding indicates that a higher A/G ratio is associated with a reduced likelihood of DR in males with diabetes. The results from NHANES underscore the importance of considering imaging-based fat distribution as a critical indicator in clinical practice.
背景：对普通糖尿病患者的脂肪分布与糖尿病视网膜病变（DR）风险之间相关性的研究有限。肥胖与糖尿病视网膜病变之间的关系仍然没有定论，这可能是由于使用了简单的人体测量方法来定义肥胖。本研究调查了美国糖尿病患者的甲状腺与蝶骨脂肪比率（A/G 比率，使用双能 X 射线吸收测量法测量）与 DR 之间的关系。方法：研究采用基于人群的横断面方法，以美国国家健康与营养调查（NHANES）2003-2006 年和 2011-2018 年的数据为基础。对患有糖尿病的参与者进行了多变量逻辑回归分析，以评估体重指数（BMI）、腰围与身高比（WHtR）和A/G比对DR患病率的影响。结果：在 比率 和 的参与者中，DR患病率分别为 和 。在对性别、年龄、种族、糖尿病病程、血红蛋白 A1c 水平、血压水平和非高密度脂蛋白胆固醇水平进行调整后，与 A/G 比值为 1.0-1.2 的人相比，A/G 比值越高（ ），患 DR 的几率越低（几率比 [OR]， : ）。在对体重指数（OR， Cl： ）和 WHtR（OR， ）进行调整后，A/G 比值较高与 DR 之间的关系仍具有统计学意义。此外，在使用特定种族的 A/G 比率三分位数进行分析时，这些关联仍具有统计学意义。在性别分层模型中，这些相关性在男性中仍然存在。 在男性中，A/G比值与糖尿病病程呈明显的负相关，经多变量调整后，这种关系依然存在（ ）。结论：一项新发现表明，A/G比值越高，男性糖尿病患者患DR的可能性越小。NHANES 的研究结果强调了在临床实践中将基于成像的脂肪分布作为关键指标的重要性。

Nutrition and Diabetes (2024)14:53; https://doi.org/10.1038/s41387-024-00308-z IF: 4.6 Q1
营养与糖尿病 (2024)14:53; https://doi.org/10.1038/s41387-024-00308-z

INTRODUCTION 引言

The prevalence of diabetes mellitus (DM) is increasing worldwide, with a projected surge by the year 2045 [1]. Diabetic retinopathy (DR) is a primary microvascular complication of DM and is a leading cause of vision impairment and blindness worldwide [2]. Studies have implicated a prevalence of DR at among newly diagnosed diabetics . Given the escalating global prevalence of diabetes, the number of individuals with DR is expected to grow, further exacerbating the negative social impact of this condition.
糖尿病（DM）的发病率在全球范围内不断上升，预计到 2045 年将激增 [1]。糖尿病视网膜病变（DR）是糖尿病的主要微血管并发症，也是全球视力受损和失明的主要原因[2]。研究表明，在新诊断的糖尿病患者中，糖尿病视网膜病变的发病率为 。鉴于全球糖尿病发病率不断攀升，预计患有 DR 的人数还会增加，从而进一步加剧这种疾病对社会的负面影响。
Obesity is a well-recognized risk factor for DM [5]. While obesity has been linked to increased risks of cardiovascular complications and kidney disease in individuals with diabetes [6], its associations with diabetic retinal complications have yielded inconclusive findings. Various studies have reported mixed results regarding the relationships between body mass index (BMI) and DR. A study indicated that a higher BMI was associated with DR [7]. The Diabetes Incidence Study in Sweden found a significant association between baseline high BMI and severe non-proliferative DR and proliferative DR over a 10 -year follow-up [8]. The similar associations were reported in the World Health Organization (WHO) study [9] and in the Diabetes Control and Complications Trial [10]. Conversely, the Singapore Diabetes Management Project [11] and other studies [12-15] have suggested that a higher BMI
肥胖是公认的糖尿病风险因素[5]。虽然肥胖与糖尿病患者心血管并发症和肾脏疾病的风险增加有关[6]，但肥胖与糖尿病视网膜并发症的关系尚无定论。关于体重指数（BMI）与糖尿病视网膜并发症之间的关系，各种研究报告的结果不一。一项研究表明，体重指数越高，视网膜病变越严重[7]。瑞典的糖尿病发病率研究发现，在 10 年的随访中，基线高体重指数与严重的非增殖性 DR 和增殖性 DR 之间存在显著关联[8]。世界卫生组织（WHO）的研究[9]和糖尿病控制与并发症试验[10]也报告了类似的关系。相反，新加坡糖尿病管理项目[11]和其他研究[12-15]表明，较高的体重指数（BMI
\footnotetext{ \脚注文本{
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Clinical Research Center for Eye Diseases, Shanghai Key Clinical Specialty, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai 200080, China. Department of Ophthalmology, Shanghai General Hospital, Shanghai 200080, China. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia. Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia. Department of Ophthalmology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. Ningde Municipal Hospital, Ningde Normal University, Ningde, China. Fujian Medical University, Fuzhou, China. These authors contributed equally: Chenxin Li, Yili Zhang,
上海交通大学医学院附属上海总医院眼科、国家眼病临床研究中心、上海市眼病临床研究中心、上海市临床重点专科、上海市眼底病重点实验室、上海市视觉科学与光医学工程中心、上海市眼病精准诊治工程中心，上海，200080。 上海总医院眼科，上海，200080。 澳大利亚眼科研究中心，维多利亚皇家眼耳医院，澳大利亚墨尔本。 澳大利亚墨尔本，墨尔本大学外科系眼科。 上海交通大学医学院附属仁济医院眼科，中国上海 200127。 宁德师范学院附属宁德市医院，中国宁德。 福建医科大学，中国福州。 这些作者的贡献相同：李晨新，张怡莉、
Received: 2 November 2023 Revised: 18 June 2024 Accepted: 20 June 2024
收到：修订：2024 年 6 月 18 日 接受：2024 年 6 月 20 日
Published online: 14 July 2024
在线出版：2024 年 7 月 14 日
may confer a protective effect against DR. Moreover, the Wisconsin Epidemiologic Study of Diabetic Retinopathy found no significant association between obesity (defined by BMI) and the risk of DR incidence or progression in type 2 DM (T2DM) [16]. Likewise, the Hoorn Study found no significant association between BMI and DR incidence in T2DM individuals [17]. Similarly, inconsistent results were observed for the associations between DR and waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) in some studies . The discrepancies in the reported association between BMI, WHR, or WHtR, and DR may be partially attributable to the use of simple anthropometric measures to define obesity, which may not fully reflect body fat accumulation and associated risk factors. Consequently, further research is necessary to better understand the role of body fat deposits in the development and progression of DR.
肥胖可能会对糖尿病视网膜病变产生保护作用。此外，威斯康星州糖尿病视网膜病变流行病学研究发现，肥胖（以体重指数定义）与 2 型糖尿病（T2DM）中 DR 的发病率或进展风险之间没有显著关联[16]。同样，霍恩研究（Hoorn Study）也发现 BMI 与 T2DM 患者的 DR 发生率之间没有明显关系[17]。同样，在一些研究 中，DR 与腰臀比（WHR）和腰高比（WHTR）之间的关系也出现了不一致的结果。所报道的 BMI、WHR 或 WHtR 与 DR 之间关系的差异可能部分归因于使用简单的人体测量方法来定义肥胖，而这些方法可能无法完全反映体内脂肪的积累和相关的风险因素。因此，有必要开展进一步研究，以更好地了解体内脂肪沉积在 DR 的发生和发展过程中的作用。
Substantial evidence supports causal relationships between excess fat in specific body regions and metabolic and cardiovascular disease [21-25]. The gynoid fat pattern, characterized by preferential fat deposition in the hip and thigh regions, has demonstrated a protective effect against cardiovascular and diabetes-related mortality and impaired glucose metabolism. Conversely, the android fat pattern, consisting primarily of adipose tissue around the trunk, is associated with the development of cardiovascular risk factors [26]. Dual-energy X-ray absorptiometry (DXA) is a well-established, non-invasive method for measuring body composition with minimal radiation exposure. It provides an accurate assessment of regional adipose tissue depots, allowing for the quantification of fat distribution, including android and gynoid fat masses. Among its clinical utilities, the android-togynoid fat ratio (A/G ratio) is reported to be associated with incident T2DM [27], insulin resistance [28], nonalcoholic fatty liver disease [29], atherosclerosis [30, 31], and atrial fibrillation [32]. Despite the clinical utility of DXA in evaluating fat distribution and its links to various health conditions, limited studies have investigated the impact of fat distribution on retinopathy in the population with diabetes. Consequently, the current study aims to fill this gap and determine the contribution of specific regional fat accumulation patterns to DR in individuals with diabetes. The DXA-assessed body composition data will be used to investigate the independent role of body fat distribution in the prevalence of DR.
大量证据表明，特定身体区域脂肪过多与代谢疾病和心血管疾病之间存在因果关系 [21-25]。雌性脂肪模式的特点是脂肪优先沉积在臀部和大腿区域，对心血管和糖尿病相关死亡率以及糖代谢受损具有保护作用。相反，主要由躯干周围脂肪组织组成的安卓脂肪模式则与心血管风险因素的发展有关[26]。双能 X 射线吸收测量法（DXA）是一种成熟的无创方法，用于测量身体成分，辐射量极低。它能准确评估区域脂肪组织沉积，量化脂肪分布，包括睾丸和阴道脂肪块。据报道，雌雄脂肪比率（A/G 比率）与 T2DM[27]、胰岛素抵抗[28]、非酒精性脂肪肝[29]、动脉粥样硬化[30, 31]和心房颤动[32]的发生有关。尽管 DXA 在评估脂肪分布及其与各种健康状况的联系方面具有临床实用性，但有关脂肪分布对糖尿病患者视网膜病变影响的研究却十分有限。因此，本研究旨在填补这一空白，确定特定区域脂肪堆积模式对糖尿病患者视网膜病变的影响。DXA 评估的身体成分数据将用于研究身体脂肪分布在 DR 患病率中的独立作用。

METHODS 方法

Data sources 数据来源

This study has presented an analysis of data obtained during the 2003-2004, 2005-2006, 2011-2012, 2013-2014, 2015-2016, and 2017-2018 cycles of the National Health and Nutrition Examination Survey (NHANES). NHANES is a complex cross-sectional survey program conducted in the United States (U.S.) by the National Center for Health Statistics (NCHS) of the Center for Disease Control and Prevention (https:// www.cdc.gov/nchs/nhanes/index.htm). NHANES conducted a complex, multistage, clustered probability sampling design and included a representative sample of the general US population of all ages. NHANES adhered to the principles of the Declaration of Helsinki, and its research procedures were approved by the NCHS Research Ethics Review Board. Informed consent was obtained from all survey participants. Ethical approval was not required for this study because the NCHS Research Ethics Review Board approved the NHANES protocols. The investigation was based on secondary analyses of de-identified data.
本研究对2003-2004年、2005-2006年、2011-2012年、2013-2014年、2015-2016年和2017-2018年周期的美国国家健康与营养调查（NHANES）所获得的数据进行了分析。NHANES 是美国疾病控制和预防中心国家卫生统计中心（NCHS）在美国（U.S. ）开展的一项复杂的横断面调查项目（https:// www.cdc.gov/nchs/nhanes/index.htm）。NHANES 采用了复杂的多阶段聚类概率抽样设计，包括美国各年龄段普通人群的代表性样本。NHANES 遵循《赫尔辛基宣言》的原则，其研究程序获得了 NCHS 研究伦理审查委员会的批准。所有调查参与者均已知情同意。本研究无需获得伦理批准，因为 NCHS 研究伦理审查委员会批准了 NHANES 协议。调查基于对去标识化数据的二次分析。

Study design and analytic sample
研究设计和分析样本

The study included participants in six NHANES cycles, covering 2003-2004, 2005-2006, 2011-2012, 2013-2014, 2015-2016, and 2017-2018. Diabetes was defined as a self-report of diabetes diagnosis by a physician or other health professional [33]. The study population included participants with diabetes. Pregnant participants, individuals aged years, individuals without information for DR, or those with invalid A/G ratio values were excluded from the analysis, leading to a final sample of 1517 participants with available data (Fig. 1).
该研究包括 2003-2004 年、2005-2006 年、2011-2012 年、2013-2014 年、2015-2016 年和 2017-2018 年六个 NHANES 周期的参与者。糖尿病的定义是由医生或其他医疗专业人员自我报告的糖尿病诊断结果[33]。研究人群包括患有糖尿病的参与者。怀孕的参与者、年龄 岁的人、没有DR信息的人或A/G比值无效的人被排除在分析之外，因此最终样本为1517名有可用数据的参与者（图1）。

Study variables 研究变量

Demographic variables included in this study were age, gender, and race/ ethnicity. The duration of diabetes and diabetic retinopathy were extracted from diabetes questionnaires [33-36].
本研究的人口统计学变量包括年龄、性别和种族/民族。糖尿病病程和糖尿病视网膜病变是从糖尿病问卷中提取的[33-36]。
Weight, height, waist circumference, and blood pressure readings were collected in mobile examination centers with standard protocols. BMI was calculated as weight in kilograms divided by height in meters squared and was classified as , and , according to the WHO definition for international BMI classification. The WHtR was determined by dividing the waist circumference by height and was categorized into three tertiles based on the data of the final sample population: the first tertile , the second tertile (0.61-0.69), and the third tertile .
体重、身高、腰围和血压读数是在流动体检中心按照标准协议采集的。体重指数的计算方法是体重（公斤）除以身高（米）的平方，根据世界卫生组织对国际体重指数分类的定义，分为 和 。WHtR通过腰围除以身高确定，根据最终样本人群的数据分为三个三等分：第一等分 、第二等分（0.61-0.69）和第三等分 。
The A/G ratio was measured by DXA. Android and gynoid regions were defined by the Hologic APEX software used in the scan analysis [37]. Tertiles of the data from the final sample population were utilized to classify the ratio into the following: first tertile ), second tertile , and third tertile ).
A/G 比值通过 DXA 测量。扫描分析中使用的 Hologic APEX 软件[37]对 Android 和 gynoid 区域进行了定义。利用最终样本人群数据的三等分法将 比率分为以下三等分：第一等分 )、第二等分 和第三等分 )。
Non-high-density lipoprotein cholesterol (non-HDL-C), a measure of total cholesterol minus high-density lipoprotein cholesterol, was used as a measure of dyslipidemia in analyses. Non-HDL-C was demonstrated to be a predictor of cardiovascular disease, and individuals with diabetes were recommended to achieve a non-HDL-C target of [38, 39]. Glycemic control was assessed by hemoglobin A1c (HbA1c) and was stratified into well-controlled ) and poorly controlled ( [7.0%]). Controlled hypertension was set as blood pressure less than 140/ 90 mmHg . Detailed descriptions of blood collection and processing procedures were provided on the NHANES website.
非高密度脂蛋白胆固醇（non-HDL-C）是总胆固醇减去高密度脂蛋白胆固醇的一个指标，在分析中被用作血脂异常的一个指标。非高密度脂蛋白胆固醇被证明是心血管疾病的预测因子，建议糖尿病患者将非高密度脂蛋白胆固醇目标值控制在 [38, 39]。血糖控制通过血红蛋白 A1c（HbA1c）进行评估，分为控制良好（ ）和控制不佳（ [7.0%]）。高血压控制在 140/90 mmHg 以下。有关血液采集和处理程序的详细说明，请访问 NHANES 网站。

Data analysis 数据分析

In sensitivity analyses, the study population was partitioned into tertiles according to ethnic subgroups in consideration of racial and ethnic variations in BMI, WHtR, and the A/G ratio. BMI was analyzed continuously and categorically (using the international WHO definitions for generalized obesity and tertiles defined within each ethnic subgroup). WHtR and the A/ ratio were assessed continuously and categorically in tertiles (using both the overall sample population tertiles and ethnic subgroup tertiles). Meanwhile, the analyses were repeated after stratifying participants by sex. To test the robustness of the findings, possible individuals with type 1 DM (T1DM) were excluded (defined as those aged years who used only insulin) and sensitivity analyses were performed on a subgroup of participants with T2DM. Additionally, the analyses were repeated after further adjustment for insulin use in the subgroup of participants with T2DM.
在敏感性分析中，考虑到 BMI、WHtR 和 A/G 比值的种族和民族差异，研究人群按民族亚群划分为三等分。对体重指数进行了连续和分类分析（采用国际世卫组织关于全身肥胖的定义以及在每个种族亚群中定义的三等分）。WHtR和A/ 比值是连续和分类三等分评估的（使用总体样本人群三等分和种族亚组三等分）。同时，按性别对参与者进行分层后重复进行分析。为检验研究结果的稳健性，排除了可能患有1型糖尿病（T1DM）的个体（定义为年龄 岁且仅使用胰岛素的个体） ，并对患有T2DM的亚组参与者进行了敏感性分析。此外，在进一步调整 T2DM 参与者亚组的胰岛素使用情况后，重复进行了分析。
Analyses were performed in RStudio for macOS (2022.02.0 + 443) using the R Package Survey (4.1-1). We used appropriate NHANES weights to account for the complex survey design of NHANES. Baseline characteristics of the participants were expressed as medians with interquartile ranges ( M (P25, P75)) and means with standard deviations (mean (SD)) for continuous variables and as percentages ( (%)) for categorical variables. The Mann-Whitney U-test and the Rao-Scott chi-square test were used for continuous and categorical variables, respectively. Multivariable logistic regression analyses were performed to assess the associations between , and the A/G ratio with the presence of DR, respectively, adjusted for potential confounding factors established in previous research. These variables included age, sex, ethnicity, diabetes duration, HbA1c level, blood pressure level, and non-high-density lipoprotein cholesterol level. Multivariable linear regression analysis assessed the associations between diabetes duration and the A/G ratio. A two-sided value of was used to determine statistical significance.
分析在 RStudio for macOS (2022.02.0 + 443) 中使用 R Package Survey (4.1-1) 进行。考虑到 NHANES 复杂的调查设计，我们使用了适当的 NHANES 权重。对于连续变量，参与者的基线特征用中位数和四分位数间距（M (P25, P75)）以及平均值和标准差（mean (SD)）表示；对于分类变量，则用百分比（ (%)）表示。连续变量和分类变量分别采用曼-惠特尼 U 检验和拉奥-斯科特卡方检验。进行了多变量逻辑回归分析，以评估 和 A/G 比值分别与是否存在 DR 之间的关系，并对先前研究中确定的潜在混杂因素进行了调整。这些变量包括年龄、性别、种族、糖尿病病程、HbA1c 水平、血压水平和非高密度脂蛋白胆固醇水平。多变量线性回归分析评估了糖尿病病程与 A/G 比值之间的关系。采用双侧 值 来确定统计学意义。

RESULTS 结果

Study population characteristics
研究对象特征

The study sample included 1517 participants, and the estimated population size was individuals. The study population contained 752 females (49.6%), and the median age (interquartile range) of the study participants was years. Table 1 reports the demographic and clinical characteristics of the participants stratified by presence/absence of DR. The prevalence of DR was among the population with diabetes included in the study. Compared with participants without DR, participants with DR were likely to have a longer duration of diabetes and a higher HbA1c level (both ).
研究样本包括 1517 名参与者，估计人口数量为 人。研究对象中有 752 名女性（占 49.6%），年龄中位数（四分位数间距）为 岁。表 1 报告了按是否患有 DR 分层的参与者的人口统计学和临床特征。在参与研究的糖尿病患者中，DR的患病率为 。与没有DR的参试者相比，患有DR的参试者的糖尿病病程可能更长，HbA1c水平可能更高（均为 ）。
Fig. 1 Flow chart of the study population. A flow chart presents the inclusion and exclusion criteria for the study. NHANES National Health and Nutrition Examination Survey, DXA dual-energy X-ray absorptiometry.
图 1 研究人群流程图。流程图显示了研究的纳入和排除标准。NHANES 国家健康与营养调查，DXA 双能 X 射线吸收测量法。

Associations of BMI and WHtR with diabetic retinopathy were not evident
体重指数和 WHtR 与糖尿病视网膜病变的关系不明显

Table 2 shows the associations between BMI, WHtR, and DR. BMI was analyzed as a continuous variable or categorical variable using WHO standards and defined tertiles in ethnic subgroups. The associations between BMI and DR were not evident in multivariable adjustments, including sex, age, ethnicity, diabetes duration, HbA1c level, blood pressure level, and non-high-density lipoprotein cholesterol level. Sex-stratified analyses found that females in the population with BMI ( ) were less likely to have DR compared with females in the population with (OR, ). The sexstratified analysis using the ethnic-specific tertiles for BMI did not show similar significant results in females. Sex-stratified analyses failed to reveal any significant association between BMI and DR in males.
表 2 显示了 BMI、WHtR 和 DR 之间的关系。BMI 作为连续变量或分类变量，采用世界卫生组织的标准进行分析，并在种族亚群中定义了三等分。在进行多变量调整（包括性别、年龄、种族、糖尿病病程、HbA1c 水平、血压水平和非高密度脂蛋白胆固醇水平）后，BMI 与 DR 之间的关系并不明显。性别分层分析发现，与 人群中的女性相比，BMI（ ）人群中的女性患DR的可能性较低（OR， ）。使用特定种族的 BMI 三等分法进行的性别分层分析在女性中未显示出类似的显著结果。性别分层分析未能发现男性的体重指数与 DR 之间存在任何显著关联。
In multivariable-adjusted and sex-stratified models, continuous or categorical analysis of WHtR failed to reveal any significant associations for DR (all ). Analyses conducted on the population with T2DM produced the same results as those with all diabetes (Table S1).
在多变量调整模型和性别分层模型中，WHtR的连续或分类分析均未发现与DR有任何显著关联（均 ）。对 T2DM 患者的分析结果与所有糖尿病患者相同（表 S1）。

Higher A/G ratio exerts a protective effect against DR
较高的 A/G 比率对 DR 有保护作用

For evaluating the contribution of fat distribution to the risk of DR, the ratio was categorized by tertiles, and multivariable logistic regression was performed (Table 3), adjusting sex, age, ethnicity, diabetes duration, HbA1c level, blood pressure level, and nonHDL-C level. The prevalence of DR was 22.2, 21.2, and among the populations with ratio , respectively. The prevalence of DR was 21.2, 21.6, and among the populations in tertile one, tertile two, and tertile three, respectively, when using ethnic-specific tertiles.
为了评估脂肪分布对 DR 风险的影响，将 比值分为三等分，并进行多变量逻辑回归（表 3），调整性别、年龄、种族、糖尿病病程、HbA1c 水平、血压水平和非 HDL-C 水平。在 比值为 的人群中，DR患病率分别为22.2、21.2和 。如果使用特定种族的三等分法，则第一、第二和第三等级人群的 DR 患病率分别为 21.2、21.6 和 。
After adjusting for several covariates, the population in the highest tertile of ratio ( ) were less likely to have DR (OR, ) compared with those in the middle A/ G ratio tertile (1.0-1.2). After further adjustment for BMI, the association between the A/G ratio and DR was unattenuated (OR, : ). Moreover, the test for trend was significant ( for trend ). After adjusting , the association between the A/G ratio and DR persisted (OR, 0.586; ), and the test for trend was significant ( for trend ). The analysis using the ethnic-specific tertiles for the A/G ratio, found that the individuals in the highest tertile of the A/G ratio were less likely to have DR (OR, : ) compared with those in the middle A/G ratio tertile. The associations persisted after further adjustment for BMI (OR, ) and WHtR (OR, : ). Moreover, analyses based on the population with T2DM yielded the same results as those with all diabetes (Table S2).
在对几个协变量进行调整后， 比值最高三等分（ ）的人群与A/G比值中间三等分（1.0-1.2）的人群相比，患DR的可能性较小（OR， ）。进一步调整体重指数后，A/G 比值与 DR 之间的关系没有减弱（OR， : ）。此外，趋势检验结果显著（ 为趋势 ）。在调整 后，A/G比值与DR之间的关系仍然存在（OR，0.586； ），趋势检验结果显著（ 为趋势 ）。使用按种族划分的A/G比值三分位数进行的分析发现，与A/G比值居中的三分位数的人相比，A/G比值最高的三分位数的人患DR的可能性较低（OR， ： ）。在进一步调整体重指数（OR， ）和 WHtR（OR， : ）后，这种关联仍然存在。此外，基于 T2DM 患者的分析结果与所有糖尿病患者的分析结果相同（表 S2）。
In sex-stratified analyses (Fig. 2), compared to the middle A/G ratio (1.0-1.2), a higher A/G ratio ( ) was associated with
在性别分层分析中（图 2），与中间 A/G 比值（1.0-1.2）相比，较高的 A/G 比值（ ）与以下因素有关
Table 1. Weighted descriptive statistics of the US population with diagnosed diabetes stratified by the presence of diabetic retinopathy.
表 1.按是否存在糖尿病视网膜病变对美国确诊糖尿病人群进行分层的加权描述性统计。
Variable 可变 Overall  总体 No DR 207) 没有 DR 207) value  值
Weighted  加权 9019027 1804216 (20.0%)
Age (years, mean [SD])
年龄（岁，平均值 [SD])		 51.3 (11.42) 51.2 (11.65) 51.8 (10.43)
Age (years, median [IQR])
年龄（岁，中位数 [IQR])		 0.468
Gender, a 性别， a
male 雄性 593 (48.8%) 172 (56.6%) 0.070
female 女性 752 (49.6%) 614 (51.2%) 138 (43.4%)
Mexican American 墨西哥裔美国人 351 (11.7%) 275 (11.9%) 76 (10.9%) 0.597
Other Hispanic 其他西班牙裔
Non-Hispanic White 非西班牙裔白人 369 (55.7%)
Non-Hispanic Black 非西班牙裔黑人 408 (16.5%) 330 (16.6%) 78 (16.0%)
Other race 其他种族 44 (11.9%)
HbA1c level,  HbA1c 水平，
(7%) 586 (54.0%) 110 (37.1%)
779 (49.4%) 592 (46.0%) 187 (62.9%)
Blood pressure level
血压水平
1094 (78.4%) 889 (79.3%) 0.204
363 (21.6%) 272 (20.7%) 91 (25.4%)
Non-HDL-C level
非高密度脂蛋白胆固醇水平
484 (42.8%) 0.245
677 (57.2%)
BMI (kg/m², mean [SD])
体重指数（千克/平方米，平均值 [SD])		 32.8 (7.17)
WHtR (median [IQR]) WHtR （中位数 [IQR]) 0.333
WHtR categories,
WHtR 类别，
Tertile  三等分 439 (34.2%) 0.693
Tertile  三等分 495 (32.5%) 397 (32.8%) 98 (31.5%)
Tertile  三等分 443 (32.6%) 351 (33.1%) 92 (30.7%)
A/G ratio (mean [SD])
A/G 比率（平均值 [SD])
A/G ratio (median [IQR])
A/G 比率（中位数 [IQR])		 0.416
A/G ratio categories,
A/G 比率类别，
Tertile  三等分 286 (18.6%) 226 (18.1%) 0.421
Tertile  三等分 517 (42.5%) 139 (45.6%)
Tertile  三等分 464 (39.4%) 111 (33.7%)
value was calculated by the Mann-Whitney -test for continuous variables and the Rao-Scott chi-square test for categorical variables.
连续变量的 值通过曼-惠特尼 检验计算，分类变量的 值通过拉奥-斯科特卡方检验计算。
SI conversion factors: To convert non-high-density lipoprotein cholesterol to mmol/L, multiply values by 0.02586 .
SI 转换系数：要将非高密度脂蛋白胆固醇换算成毫摩/升，将数值乘以 0.02586。
Non-HDL-C non-high-density lipoprotein cholesterol, DM diabetes mellitus, HbA1c hemoglobin A1c, BMI body mass index, WHtR waist-to-height ratio, ratio android-to-gynoid fat ratio.
非高密度脂蛋白胆固醇（Non-HDL-C）、非高密度脂蛋白胆固醇（DM）、糖尿病（Diabetes mellitus）、血红蛋白 A1c（HbA1c）、体重指数（BMI）、腰围与身高比（WHtR）、甲状腺与睾丸脂肪比（ ratio android-to-gynoid fat ratio）。
Unweighted counts (weighted percent) for categorical variables.
分类变量的非加权计数（加权百分比）。
lower odds of DR in males with diabetes (OR, : 0.291-0.824), but not in females. The associations persisted after adjustment for BMI (OR, 0.495 ; 95% CI: 0.290-0.843) in males. Meanwhile, the associations remained after adjusting
男性糖尿病患者发生 DR 的几率较低（OR， ：0.291-0.824），而女性糖尿病患者发生 DR 的几率较低。在调整体重指数（OR，0.495；95% CI：0.290-0.843）后，男性糖尿病患者的相关性依然存在。同时，在对体重指数（OR，0.495；95% CI：0.290-0.843）进行调整后，这种关联仍然存在。
WHtR (OR, ) in males. The sexstratified analysis using the ethnic-specific tertiles for the A/G ratio found that the male individuals in the highest tertile of the A/G ratio were less likely to have DR (OR, ,
男性的 WHtR（OR， ）。使用特定种族的 A/G 比值三等分法进行的性别分层分析发现，A/G 比值最高三等分法中的男性患 DR 的可能性较低（OR， 、
Table 2. Multivariable associations between BMI and waist-to-height ratio with the presence of diabetic retinopathy in the studied population and stratified by sex.
表 2.研究人群中体重指数和腰围身高比与糖尿病视网膜病变之间的多变量关系，并按性别进行分层。
Prevalence 流行率 Overall OR (95% CI)
总体 OR（95% CI）		 Male OR (  男性 OR ( ) Female OR  女性 OR
BMI level 体重指数水平
1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料]
for trend  趋势 0.970 0.954 0.742
BMI tertiles by ethnicity
按种族划分的体重指数分层
Tertile 3 第 3 梯队
for trend  趋势 0.445 0.314 0.779
BMI (Per unit increase)
体重指数（每增加一个单位）
WHtR level WHtR 级别
WHtR tertiles by ethnicity
按种族分列的 WHtR tertiles
Tertile 1 第 1 层 1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料]
Tertile 2 第 2 层
Tertile 3 第 3 梯队
for trend  趋势 0.892 0.792 0.634
WHtR (Per 0.1-unit increase)
WHtR （每增加 0.1 个单位）
Adjusted for sex, age, race/ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, non-high-density lipoprotein cholesterol level. Stratified models are adjusted for covariates not stratified on.
根据性别、年龄、种族/族裔、糖尿病病程、血红蛋白 A1c 水平、血压水平、非高密度脂蛋白胆固醇水平进行调整。分层模型对未分层的协变量进行了调整。
BMI body mass index, WHtR waist-to-height ratio, OR odds ratio, Cl confidence interval.
BMI 体重指数，WHtR 腰围身高比，OR 机率比，Cl 置信区间。
Table 3. Multivariable associations between ratio and the presence of diabetic retinopathy.
表 3. 比值与糖尿病视网膜病变之间的多变量关系。
A/G ratio A/G 比率 Prevalence (%) 流行率（%） Odds ratio  赔率
Model  型号 Model  型号 Model  型号
Tertiles categorized by overall population
按总人口分类的分层
1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料]
for trend  趋势 0.061 0.047 0.046
Tertile 2 第 2 层 1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料] 1 [Reference] 1 [参考资料]
Tertile 1 第 1 层
Tertile 3 第 3 梯队
for trend  趋势 0.106 0.088 0.087
A/G ratio (per 0.1 -unit increase)
A/G 比率（每增加 0.1 单位）
Model 1: Adjusted for sex, age, race/ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, non-high-density lipoprotein cholesterol level.
模型 1：根据性别、年龄、种族/民族、糖尿病病程、血红蛋白 A1c 水平、血压水平、非高密度脂蛋白胆固醇水平进行调整。
Model 2: Model 1+body mass index.
模型 2：模型 1+ 体重指数。
Model 3: Model 1+waist-to-height ratio.
模型 3：模型 1+ 腰高比。
ratio android-to-gynoid fat ratio, odds ratio, Cl confidence interval.
甲状腺与腮腺脂肪比率， 几率，Cl置信区间。
) compared with those in the middle A/G ratio tertile. The associations persisted after further adjustment for BMI (OR, Cl: 0.281-0.858) and WHtR (OR, Cl: 0.292-0.928). The sex-stratified analyses failed to reveal any significant associations for DR (all ) in female individuals.
）。在对体重指数（OR， Cl：0.281-0.858）和 WHtR（OR， Cl：0.292-0.928）进行进一步调整后，相关性依然存在。性别分层分析未能发现女性与 DR（均为 ）有任何显著关联。
The studies based on the population with T2DM found similar effective results as those with all diabetes (Table S3). Additionally, the associations remained significant after further adjustment for insulin use within the population with T2DM (Table S4).
以 T2DM 患者为研究对象的研究发现了与所有糖尿病患者相似的有效结果（表 S3）。此外，在进一步调整 T2DM 患者使用胰岛素的情况后，相关性仍然显著（表 S4）。
Fig. 2 Multivariable associations between A/G ratio and presence of diabetic retinopathy, stratified by sex. Values are shown as odds ratios (OR) and confidence interval ( ). The model was adjusted for age, race/ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, and non-high-density lipoprotein cholesterol level. Model 1: Adjusted for age, race/ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, and non-high-density lipoprotein cholesterol level. Model 2: Model 1+body mass index. Model 3: Model waist-to-height ratio.
图 2 按性别分层的 A/G 比值与糖尿病视网膜病变之间的多变量关联。数值以几率比（OR）和 置信区间（ ）表示。该模型根据年龄、种族/民族、糖尿病病程、血红蛋白 A1c 水平、血压水平和非高密度脂蛋白胆固醇水平进行了调整。模型 1：根据年龄、种族/族裔、糖尿病病程、血红蛋白 A1c 水平、血压水平和非高密度脂蛋白胆固醇水平进行调整。模型 2：模型 1+ 体重指数。模型3：模型 腰围与身高比。
Table 4. Linear regression for association between A/G ratio and diabetes duration in the studied population and stratified by sex.
表 4.研究人群中 A/G 比值与糖尿病病程关系的线性回归（按性别分层）。
A/G ratio A/G 比率 DM duration (per-10-year increment)
管理部持续时间（每 10 年递增）
Overall 总体情况 Male 男 Female 女性
Beta  测试版 P value P 值 Beta  测试版 P value P 值 Beta (95% CI)
Model 1 模型 1 0.004 0.005 P value P 值
Model 2 模型 2 0.009 0.018 0.217
Model 3 模型 3 0.056 0.045 0.527
Model 1: Adjusted for age, sex, race/ethnicity.
模型 1：根据年龄、性别、种族/人种进行调整。
Model 2: Model 1+ hemoglobin A1c level.
模型 2：模型 1+ 血红蛋白 A1c 水平。
Model 3: Model 2+ blood pressure level, non-high-density lipoprotein cholesterol level.
模型 3：模型 2+ 血压水平、非高密度脂蛋白胆固醇水平。
Stratified models are adjusted for covariates not stratified on.
分层模型对未分层的协变量进行了调整。
DM diabetes mellitus, confidence interval.
DM 糖尿病， 置信区间。

The A/G ratio exhibits a negative correlation with diabetes duration
A/G 比率与糖尿病病程呈负相关

Table 4 depicts the linear associations between fat depots and diabetes duration. After adjustment for demographic factors, the coefficient for diabetes duration suggested that a per-10-year increase in DM was associated with a 0.018 decrease in the A/G ratio ( ). Similar inverse associations were observed after additional adjustments (Table 4; models 2 and 3). In sex-stratified analyses, a per-10-year increase in DM was associated with a 0.026 decrease in the A/G ratio among the male population ( ). The inverse relationship persisted after multivariable adjustments (Table 4; models 2 and 3). The association was non-significant in the female population.
表 4 描述了脂肪层与糖尿病病程之间的线性关系。在对人口统计学因素进行调整后，糖尿病持续时间的系数表明，糖尿病每增加10年，A/G比值就会下降0.018（ ）。经过额外调整后，也观察到了类似的反比关系（表 4；模型 2 和 3）。在性别分层分析中，在男性人群中，糖尿病每增加 10 年与 A/G 比值下降 0.026 有关 ( )。经多变量调整后，这种反比关系依然存在（表 4；模型 2 和 3）。这一关系在女性人群中并不显著。

DISCUSSION 讨论

In this population-based cross-sectional study, we investigated the associations between body fat distribution, as assessed by DXA, and the prevalence of DR. This study has presented new information that the higher ratio is associated with a reduced likelihood of DR presence, independent of BMI and WHtR, although the A/G ratio-DR association is attenuated in females. The results provided valuable insights by highlighting the associations between imaging-based body fat distribution and DR, even after accounting for anthropometric obesity indicators, indicating that fat distribution may play an independent role in the pathophysiology of DR in the population with diabetes.
在这项基于人群的横断面研究中，我们调查了通过 DXA 评估的体脂分布与 DR 患病率之间的关系。这项研究提供了新的信息，即较高的 比值与出现DR的可能性降低有关，而与体重指数和WHtR无关，尽管A/G比值与DR的关联在女性中有所减弱。研究结果提供了有价值的见解，强调了基于成像的体脂分布与 DR 之间的关联，即使在考虑人体测量肥胖指标之后也是如此，这表明脂肪分布可能在糖尿病人群的 DR 病理生理学中发挥着独立作用。
The association between obesity and DR has been a subject of debate for decades, with inconclusive evidence supporting the relationship between obesity indicators and DR. Studies have reported conflicting results, with some indicating that obesity, measured by higher BMI, is a significant independent risk factor for developing DR [7-10], while others have reported it to be protective [11-15], or have found no significant associations [16, 17] with DR. The associations between DR and WHtR were also inconsistent [19, 20]. To shed light on this relationship, the study
几十年来，肥胖与 DR 之间的关系一直是一个争论不休的话题，没有确凿的证据支持肥胖指标与 DR 之间的关系。研究报告的结果相互矛盾，一些研究表明，以较高体重指数衡量的肥胖是罹患 DR 的重要独立风险因素[7-10]，而另一些研究则报告称肥胖具有保护作用[11-15]，或发现肥胖与 DR 没有显著关联[16, 17]。DR 与 WHtR 之间的关系也不一致 [19，20]。为了阐明这种关系，本研究
evaluated the impact of anthropometric obesity indicators (BMI and WHtR ) and body fat distribution evaluated by DXA on the prevalence of DR in the population of 1517 participants with diabetes from the NHANES. When analyzing BMI according to WHO standards, the results showed that overweight females with diabetes were less likely to have DR compared with females in the population with a (OR, ). However, no similar result was found in female participants when using the ethnic-specific tertiles for BMI, and no significant association between BMI and DR was found among males. Moreover, no significant association was found between WHtR and the prevalence of DR.
该研究评估了人体测量肥胖指标（BMI和WHtR）和DXA评估的体脂分布对1517名NHANES糖尿病参与者中DR患病率的影响。根据世界卫生组织的标准对体重指数进行分析，结果显示，与 （OR， ）的女性糖尿病患者相比，超重的女性糖尿病患者患 DR 的可能性较低。然而，在使用特定种族的体重指数三等分法时，在女性参与者中没有发现类似的结果，在男性中也没有发现体重指数与 DR 之间有显著的关联。此外，WHtR 与 DR 患病率之间也没有发现明显的关联。
Interestingly, the study revealed that a higher A/G ratio was associated with lower DR prevalence, although the A/G ratio-DR association was attenuated in female participants. These associations persisted after adjusting for BMI and WHtR, suggesting that BMI or WHtR may not accurately estimate the risk of DR. The findings presented robust associations in sensitivity analyses using the ethnic-specific tertile for the A/G ratio. The study highlights the complexity of the relationship between obesity and DR and emphasizes the importance of considering other factors, such as body fat distribution, to better understand this association.
有趣的是，研究显示，较高的 A/G 比值与较低的 DR 患病率相关，尽管女性参与者的 A/G 比值与 DR 的关联有所减弱。在调整体重指数和 WHtR 后，这些关联仍然存在，这表明体重指数或 WHtR 可能无法准确估计 DR 的风险。在使用特定种族的 A/G 比值三分位数进行的敏感性分析中，研究结果显示了稳健的相关性。该研究强调了肥胖与DR之间关系的复杂性，并强调了考虑其他因素（如体脂分布）以更好地理解这种关联的重要性。
Android fat is the accumulation of adipose tissue around the trunk, while gynoid fat refers to the fat deposited in the subcutaneous depot of hips, thighs, and buttocks [21]. A higher A/G ratio is typically associated with an android pattern of fat accumulation, characterized by increased visceral adipose tissue (VAT) around the trunk or decreased subcutaneous adipose tissue (SAT) around the hips. Interestingly, subcutaneous fat, rather than VAT, has been reported to be associated with the site of inflammation onset in the elderly [32, 41]. Additionally, agerelated telomere length shortening in SAT, not VAT, leads to an increase in senescent cell burden [41]. Given that individuals with DR are often older and that inflammation plays a role in the pathogenesis of microvascular complications, it is plausible that gynoid fat may pose a higher risk of DR in the elderly when compared to android fat. However, it is essential to acknowledge that the relationship between body fat distribution, inflammation, and aging is complex, and research is needed to fully understand their impact on DR risk.
安卓脂肪是指躯干周围堆积的脂肪组织，而妇科脂肪则是指臀部、大腿和臀部皮下堆积的脂肪[21]。较高的 A/G 比值通常与安卓模式的脂肪堆积有关，其特点是躯干周围的内脏脂肪组织（VAT）增加或臀部周围的皮下脂肪组织（SAT）减少。有趣的是，有报道称皮下脂肪而非内脏脂肪组织与老年人炎症的发病部位有关 [32，41]。此外，皮下脂肪（而非增值脂肪）中与年龄相关的端粒长度缩短会导致衰老细胞数量增加 [41]。鉴于 DR 患者通常年龄较大，而炎症在微血管并发症的发病机制中扮演着重要角色，因此与甲状腺脂肪相比，雌性脂肪可能会给老年人带来更高的 DR 风险。然而，必须承认的是，体脂分布、炎症和衰老之间的关系是复杂的，需要进行研究以充分了解它们对 DR 风险的影响。
Additionally, the current analyses of the ratio in relation to the duration of DM revealed a significant association, indicating that a prolonged duration of DM was linked to a lower A/G ratio in males. This finding suggests that diabetes may alter the pattern of fat deposition in males, likely through its impact on sex hormones. In males, lipoprotein lipase activity is higher in abdominal adipose tissues, and testosterone inhibits its activity in femoral subcutaneous fat, resulting in the android physique typically observed in males. At least of males with T2DM have subnormal testosterone levels , which may contribute to changes in fat distribution. Studies have shown that hypogonadal men have increased fatty acid storage in the lower body subcutaneous area and higher activity of femoral adipose tissue acyl-CoA synthetase, indicating that chronic testosterone deficiency in males with diabetes may lead to fat redistribution via adipocyte enzymes [44]. Moreover, previous research demonstrated that males with diabetes tend to have higher estradiol levels than non-diabetic counterparts [45-47]. Elevated estradiol and lower testosterone levels may contribute to the gynoid body morphology and decreasing A/G ratio observed in males with diabetes. Further investigations are necessary to explore the role and mechanisms of hormone-mediated fat redistribution in males with diabetes, as the change in preferential fat accumulation in males may reflect the progression of DM and be associated with DR. On the other hand, remarkable adipose redistribution following menopause in females might attenuate the association between the A/G ratio and the duration of DM. Therefore, it is reasonable to understand that males with diabetes who have a higher A/G ratio are less likely to have DR, and direct measurement of regional fat may offer a more accurate assessment of retinopathy risk.
此外，目前对 比率与糖尿病持续时间的关系进行的分析表明，两者之间存在显著关联，表明糖尿病持续时间长与男性的A/G比率较低有关。这一发现表明，糖尿病可能会通过影响性激素而改变男性的脂肪沉积模式。男性腹部脂肪组织中的脂蛋白脂肪酶活性较高，而睾酮会抑制股皮下脂肪中脂蛋白脂肪酶的活性，从而导致男性典型的甲状腺体质。至少 有T2DM的男性睾酮水平低于正常 ，这可能导致脂肪分布的变化。研究表明，性腺功能低下的男性下半身皮下脂肪酸储存增加，股脂肪组织酰基-CoA 合成酶活性较高，这表明男性糖尿病患者长期睾酮缺乏可能会通过脂肪细胞酶导致脂肪重新分布[44]。此外，先前的研究表明，男性糖尿病患者的雌二醇水平往往高于非糖尿病患者 [45-47]。雌二醇水平升高和睾酮水平降低可能是导致男性糖尿病患者出现妇科体型和 A/G 比率下降的原因。有必要开展进一步研究，探讨激素介导的脂肪重新分布在男性糖尿病患者中的作用和机制，因为男性偏好脂肪堆积的变化可能反映了糖尿病的进展，并与 DR 有关。另一方面，女性绝经后显著的脂肪再分布可能会减弱 A/G 比值与糖尿病持续时间之间的联系。 因此，我们有理由认为，A/G 比率较高的男性糖尿病患者患 DR 的可能性较低，而直接测量区域脂肪可能会更准确地评估视网膜病变的风险。
This study presents a groundbreaking finding, showing that the DXA-measured A/G ratio, a comprehensive index of regional body fat distribution, served as an independent marker for DR. It is argued that relying solely on BMI or WHtR is insufficient to assess or manage the microvascular risk associated with increased adiposity in the population with diabetes. Current analysis suggests that the fat deposition pattern index, A/G ratio, serves as an independent and superior discriminator compared to anthropometric obesity indices. Based on the compelling evidence from the NHANES, this study strongly advocates for fat distribution to be considered as a vital sign in clinical practice.
这项研究提出了一项突破性的发现，表明通过 DXA 测量的 A/G 比值（身体脂肪区域分布的综合指数）可作为 DR 的独立标记。有观点认为，仅仅依靠体重指数或 WHtR 不足以评估或管理糖尿病患者中与脂肪增加相关的微血管风险。目前的分析表明，与人体测量肥胖指数相比，脂肪沉积模式指数（A/G 比值）是一个独立且更优越的判别指标。基于 NHANES 提供的有力证据，本研究强烈主张将脂肪分布作为临床实践中的一项重要指标。
This study has several limitations that should be acknowledged. First, due to the limited proportion of participants with T1DM, the findings primarily apply to the T2DM population. Second, the information on DR was extracted from diabetes questionnaires. The methodology used in this study was aligned with previous studies [33-36] to ensure consistency and comparability. Third, being a cross-sectional study, it is challenging to establish causeand-effect relationships; nevertheless, the findings provide valuable insights for clinicians in managing diabetic complications. Fourth, it is important to note that only the 2003-2006 cycles of NHANES administered DXA to participants aged 60 and older. Among 1517 participants in the study population, 375 were aged 60 and above, representing a weighted estimate of 1470182 individuals. The weighted calculations of the complex sampling strategy and the adjustment for age in multivariable logistic regression analysis mitigate the impact on the representativity of the findings. On the positive side, a significant strength of this study is its representative sample size. NHANES provides generalizable data on a multiethnic population that is nationally representative of the U.S. Moreover, the biochemical data and questionnaire responses were homogeneously collected by trained personnel, enhancing the reliability of the study's data collection process.
本研究有几个局限性，应予以承认。首先，由于 T1DM 参与者比例有限，研究结果主要适用于 T2DM 群体。其次，有关 DR 的信息是从糖尿病问卷中提取的。本研究采用的方法与之前的研究[33-36]一致，以确保一致性和可比性。第三，作为一项横断面研究，确定因果关系具有挑战性；然而，研究结果为临床医生管理糖尿病并发症提供了宝贵的见解。第四，值得注意的是，只有 2003-2006 年周期的 NHANES 对 60 岁及以上的参与者进行了 DXA 检测。在 1517 名研究对象中，有 375 人年龄在 60 岁及以上，加权估计为 1470182 人。复杂抽样策略的加权计算和多变量逻辑回归分析中的年龄调整减轻了对研究结果代表性的影响。从积极的方面来看，这项研究的一个重要优势是其样本量具有代表性。此外，生化数据和问卷答复均由经过培训的人员统一收集，提高了研究数据收集过程的可靠性。

CONCLUSION 结 论

The novel finding of an association between higher ratio and the presence of DR, independent of BMI and WHtR, underscores the importance of fat distribution as a critical factor in DR. This study highlights that imaging-based fat distribution serves as a more clinically significant marker among individuals with diabetes. Furthermore, it suggests that considering how fat is distributed in the body could be crucial in assessing the risk of retinopathy in the population with diabetes. Further research is warranted to gain a deeper understanding of the mechanisms behind this relationship and its implications for diabetes management and risk assessment.
较高的 比值与DR之间存在关联，而与体重指数（BMI）和WHtR无关，这一新颖发现强调了脂肪分布作为DR关键因素的重要性。这项研究强调，基于成像的脂肪分布是糖尿病患者中更具临床意义的标志物。此外，研究还表明，考虑脂肪在体内的分布情况对于评估糖尿病患者视网膜病变的风险至关重要。为了更深入地了解这种关系背后的机制及其对糖尿病管理和风险评估的影响，我们有必要开展进一步的研究。

DATA AVAILABILITY 数据可用性

Data described in the manuscript and analytic code will be made available upon request pending.
手稿中描述的数据和分析代码将在收到请求后提供。

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AUTHOR CONTRIBUTIONS 作者贡献

ZZ and YC designed research; , and MM conducted research; , and BL analyzed data; CL wrote the paper; CL and XX revised the manuscript. ZZ had primary responsibility for final content. All authors read and approved the final manuscript.
ZZ和YC设计研究； 和MM进行研究； 和BL分析数据；CL撰写论文；CL和XX修改手稿。ZZ 对最终内容负主要责任。所有作者阅读并批准了最终稿件。

FUNDING 资金

This study was supported by grants from the National Natural Science Foundation of China (Nos. 82271111 , received by Zhi Zheng). The sponsor or funding organization had no role in the design or conduct of this research.
本研究得到了国家自然科学基金的资助（编号：82271111，郑智获得）。赞助方或资助机构在本研究的设计和实施过程中未发挥任何作用。

COMPETING INTERESTS 利益冲突

The authors declare no competing interests.
作者声明不存在利益冲突。
C. Li et al.
C.Li et al.

ADDITIONAL INFORMATION 其他信息

Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41387-024-00308-z IF: 4.6 Q1 .
补充信息 在线版本包含补充材料，可从 https://doi.org/10.1038/s41387-024-00308-z 获取。
Correspondence and requests for materials should be addressed to Xiaoyin Xu , Yongdong Chen or Zhi Zheng.
通讯和资料索取请联系：Xiaoyin Xu , Yongdong Chen 或 Zhi Zheng。
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(c) The Author(s) 2024
(c) 作者 2024 年