肌肉脂肪比与2型糖尿病患者代谢相关脂肪性肝病关系的性别差异：一项回顾性研究

Gender differences in the association between muscle-to-fat ratio and metabolic dysfunction-associated fatty liver disease in patients with type 2 diabetes mellitus：a retrospective study

摘要

目的: 探讨肌肉脂肪比(muscle-to-fat ratio，MFR)与2型糖尿病(type 2 diabetes mellitus，T2DM)患者代谢相关脂肪性肝病(metabolic dysfunction-associated fatty liver disease，MAFLD)的关系，并分析其性别差异及诊断效能。方法: 回顾性纳入2023年9月—2024年8月于南京医科大学第一附属医院内分泌科住院的T2DM患者，通过电子病历系统收集临床资料，生物电阻抗分析测定体成分，计算MFR[全身骨骼肌质量(kg)/全身脂肪质量(kg)]，FibroScan检测受控衰减参数(controlled attenuation parameter，CAP)与肝脏硬度值(liver stiffness measurement，LSM)。根据患者是否合并MAFLD，分为Non-MAFLD组和MAFLD组。按性别将MFR进行三分位数分组，采用Logistic回归及趋势性检验分析MFR与MAFLD的关联，通过受试者工作特征(receiver operating characteristic，ROC)曲线评估MFR对MAFLD的诊断效能。结果: 共筛查2 056例T2DM患者，根据纳入排除标准最终纳入448例，其年龄为(55.33 ± 12.00)岁，体重指数(body mass index，BMI)为(25.13 ± 3.51)kg/m²。MAFLD总体患病率为62.5%(280/448)，其中，男性患病率(59.9%，187/312)低于女性(68.4%，93/136)。MAFLD组(n=280)MFR低于Non-MAFLD组(n=168)[1.01(0.77，1.24)vs. 1.29(0.96，1.74)，P<0.001]。MFR分组分析显示，随着MFR升高，MAFLD患病率下降(P<0.001)。多因素Logistic回归显示，与MFR最高组相比，男性最低组和中间组发生MAFLD的风险显著增加[OR(95% CI)分别为3.36(1.49~7.57)和2.03(1.02~4.03)]，且存在线性趋势(P for trend=0.001)；而女性仅中间组风险显著增加(OR=3.53，95% CI：1.05~11.88)，未观察到线性趋势(P for trend=0.699)。此外，中介分析显示BMI在女性中中介效应显著(效应值=-3.59，Bootstrap 95% CI：-7.23~-1.09)。MFR诊断MAFLD的ROC曲线下面积，男性为0.766(截断值1.22)，女性为0.711(截断值0.78)。相关性分析显示，不同性别MFR均与肥胖指标、胰岛素抵抗指数、CAP、LSM负相关；而年龄仅与女性MFR负相关，血脂、尿酸、肝酶仅与男性MFR负相关。结论: MFR与T2DM患者MAFLD风险独立相关，其关联模式存在性别差异，提示临床管理需考虑性别因素。

Abstract

Objective: To investigate the association between the muscle-to-fat ratio(MFR)and metabolic dysfunction-associated fatty liver disease(MAFLD)in patients with type 2 diabetes mellitus(T2DM)，and to evaluate its gender differences and diagnostic performance. Methods: A retrospective study was conducted on T2DM patients hospitalized in the Department of Endocrinology at the First Affiliated Hospital of Nanjing Medical University from September 2023 to August 2024. Clinical data were collected from the electronic medical record system. Body composition was measured by bioelectrical impedance analysis，and MFR was calculated as total skeletal muscle mass(kg)/total fat mass(kg). We measured controlled attenuation parameter(CAP)and liver stiffness measurement(LSM)via FibroScan. Patients were divided into the non-MAFLD and MAFLD groups according to whether they had MAFLD. MFR was stratified into gender-specific tertiles. Its association with MAFLD was analyzed using logistic regression and trend tests，with diagnostic performance evaluated via receiver operating characteristic(ROC)curve analysis. Results: A total of 2 056 T2DM patients were screened，of whom 448 met the inclusion criteria and were enrolled. The mean age was 55.33 ± 12.00 years，and the mean body mass index(BMI)was 25.13 ± 3.51 kg/m². The overall prevalence of MAFLD was 62.5%(280/448). The prevalence was lower in males(59.9%，187/312)than in females(68.4%，93/136). The MFR was significantly lower in the MAFLD group(n=280)than in the non-MAFLD group(n=168)[1.01(0.77，1.24)vs. 1.29(0.96，1.74)，P<0.001]. MFR tertile analysis showed a decreasing prevalence of MAFLD with increasing MFR(P<0.001). Multivariable logistic regression revealed gender-specific associations. Compared to the highest MFR tertile，males in the lowest and middle tertiles had a significantly higher risk of MAFLD[OR(95% CI)：3.36(1.49-7.57)and 2.03(1.02-4.03)，respectively]，with a significant linear trend(P for trend = 0.001). In contrast，among females，only the middle tertile showed a significantly increased risk[OR(95% CI)：3.53(1.05-11.88)]，with no linear trend(P for trend = 0.699). Additionally，mediation analysis demonstrated a statistically significant indirect effect of BMI in females(effect=-3.59，Bootstrap 95% CI：-7.23--1.09). The area under the ROC curve of MFR for diagnosing MAFLD was 0.766(cut-off value：1.22)in males and 0.711(cut-off value：0.78)in females. Correlation analysis indicated that MFR was negatively correlated with obesity indices，homeostatic model assessment of insulin resistance，CAP，and LSM in both genders. However，age was negatively correlated with MFR only in females，whereas blood lipids，uric acid，and liver enzymes showed inverse correlations only in males. Conclusion: MFR is independently associated with MAFLD risk in patients with T2DM，and this association exhibits distinct gender-specific patterns，highlighting the importance of considering gender in clinical management.

关键词

肌肉脂肪比 / 代谢相关脂肪性肝病 / 2型糖尿病 / 生物电阻抗分析 / 性别差异

Key words

muscle-to-fat ratio / metabolic dysfunction-associated fatty liver disease / type 2 diabetes mellitus / bioelectrical impedance analysis / gender differences

参考文献

[1] 范建高, 徐小元, 南月敏, 等. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J]. 实用肝脏病杂志, 2024, 27(4):494-510

[2] FAN J G, XU X Y, NAN Y M, et al. Guidelines for the prevention and treatment of metabolic dysfunction—associated(non—alcoholic)fatty liver disease(Version 2024)[J]. Journal of Pratical Hepatology, 2024, 27(4):494-510

[3] TARGHER G, COREY K E, BYRNE C D, et al. The complex link between NAFLD and type 2 diabetes mellitus—mechanisms and treatments[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(9):599-612

[4] KAYA E, YILMAZ Y. Metabolic—associated fatty liver disease(MAFLD)：a multi—systemic disease beyond the liver[J]. J Clin Transl Hepatol, 2022, 10(2):329-338

[5] TACKE F, HORN P, WAI—SUN WONG V, et al. EASL—EASD—EASO clinical practice guidelines on the management of metabolic dysfunction—associated steatotic liver disease(MASLD)[J]. J Hepatol, 2024, 81(3):492-542

[6] FANG D, TANG W J, ZHAO X Y, et al. Gender differences in the association of body composition and biopsy—proved nonalcoholic steatohepatitis[J]. Hepatol Int, 2022, 16(2):337-347

[7] KIM H S, LEE J, KIM E H, et al. Association of myosteatosis with nonalcoholic fatty liver disease，severity，and liver fibrosis using visual muscular quality map in computed tomography[J]. Diabetes Metab J, 2023, 47(1):104-117

[8] IZZO A, MASSIMINO E, RICCARDI G, et al. A narrative review on sarcopenia in type 2 diabetes mellitus：prevalence and associated factors[J]. Nutrients, 2021, 13(1):183

[9] MAI Z L, CHEN Y F, MAO H, et al. Association between the skeletal muscle mass to visceral fat area ratio and metabolic dysfunction—associated fatty liver disease：a cross—sectional study of NHANES 2017—2018[J]. J Diabetes, 2024, 16(6):e13569

[10] SEO Y G, SONG H J, SONG Y R. Fat—to—muscle ratio as a predictor of insulin resistance and metabolic syndrome in Korean adults[J]. J Cachexia Sarcopenia Muscle, 2020, 11(3):710-725

[11] LIU D X, ZHONG J N, RUAN Y T, et al. The association between fat—to—muscle ratio and metabolic disorders in type 2 diabetes[J]. Diabetol Metab Syndr, 2021, 13(1):129

[12] GOOSSENS G H, JOCKEN J W E, BLAAK E E. Sexual dimorphism in cardiometabolic health：the role of adipose tissue，muscle and liver[J]. Nat Rev Endocrinol, 2021, 17(1):47-66

[13] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)(上)[J]. 中国实用内科杂志, 2021, 41(8):668-695

[14] Chinese Diabetes Society. Chinese guideline for the prevention and treatment of type 2 diabetes mellitus(2020 edition)[J]. Chinese Journal of Pratical Internal Medicine, 2021, 41(8):668-695

[15] MATTHEWS D R, HOSKER J P, RUDENSKI A S, et al. Homeostasis model assessment：insulin resistance and beta—cell function from fasting plasma glucose and insulin concentrations in man[J]. Diabetologia, 1985, 28(7):412-419

[16] EDDOWES P J, SASSO M, ALLISON M, et al. Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease[J]. Gastroenterology, 2019, 156(6):1717-1730

[17] 中国高血压防治指南修订委员会, 高血压联盟(中国), 中国医疗保健国际交流促进会高血压分会, 等. 中国高血压防治指南(2024年修订版)[J]. 中华高血压杂志, 2024, 32(7):603-700

[18] Revision Committee of Chinese Guidelines for Hypertension Management, Chinese Hypertension League, Hypertension Branch of China International Exchange and Promote Association for Medical and Health Care, et al. Chinese guidelines for hypertension management(2024 revision)[J]. Chinese Journal of Hypertension, 2024, 32(7):603-700

[19] EN LI CHO E, ANG C Z, QUEK J, et al. Global prevalence of non—alcoholic fatty liver disease in type 2 diabetes mellitus：an updated systematic review and meta—analysis[J]. Gut, 2023, 72(11):2138-2148

[20] CAO Y T, ZHANG W H, LOU Y, et al. Sex—and reproductive status—specific relationships between body composition and non—alcoholic fatty liver disease[J]. BMC Gastroenterol, 2023, 23(1):364

[21] KIRK B, FEEHAN J, LOMBARDI G, et al. Muscle，bone，and fat crosstalk：the biological role of myokines，osteokines，and adipokines[J]. Curr Osteoporos Rep, 2020, 18(4):388-400

[22] ZHU X P, HUANG Q X, MA S, et al. Presence of sarcopenia identifies a special group of lean NAFLD in middle—aged and older people[J]. Hepatol Int, 2023, 17(2):313-325

[23] XU G Q, WU Y Y, CHEN J, et al. The relationship between muscle mass and fat content in body composition and non—alcoholic fatty liver disease in the Chinese general population：a cross—sectional study[J]. Front Med, 2024, 11:1384366

[24] XING M C, NI Y L, ZHANG Y, et al. The relationship between skeletal muscle mass to visceral fat area ratio and metabolic dysfunction—associated fatty liver disease subtypes in middle—aged and elderly population：a single—center retrospective study[J]. Front Nutr, 2023, 10:1246157

[25] OSAKA T, HASHIMOTO Y, OKAMURA T, et al. Reduction of fat to muscle mass ratio is associated with improvement of liver stiffness in diabetic patients with non—alcoholic fatty liver disease[J]. J Clin Med, 2019, 8(12):2175

[26] GHELLER B J, RIDDLE E S, LEM M R, et al. Understanding age—related changes in skeletal muscle metabolism：differences between females and males[J]. Annu Rev Nutr, 2016, 36:129-156

[27] GADO M, TSAOUSIDOU E, BORNSTEIN S R, et al. Sex—based differences in insulin resistance[J]. J Endocrinol, 2024, 261(1):e230245

[28] BIAGETTI B, SIMÓ R. GH/IGF—1 abnormalities and muscle impairment：from basic research to clinical practice[J]. Int J Mol Sci, 2021, 22(1):415

[29] DISTEFANO J K. NAFLD and NASH in postmenopausal women：implications for diagnosis and treatment[J]. Endocrinology, 2020, 161(10):bqaa134

[30] HOFFMANN J, SCHMIDT J, THIELE J, et al. The role of adipose tissue in liver fat accumulation：a sex—specific analysis in an exploratory cross—sectional study[J]. Lipids Health Dis, 2025, 24(1):376

[31] ZHU J X, HU Z Y, LUO Y F, et al. Diabetic peripheral neuropathy：pathogenetic mechanisms and treatment[J]. Front Endocrinol, 2023, 14:1265372

[32] BAROUKI R, SAMSON M, BLANC E B, et al. The exposome and liver disease—how environmental factors affect liver health[J]. J Hepatol, 2023, 79(2):492-505

[33] FANG W H, YANG J R, LIN C Y, et al. Accuracy augmentation of body composition measurement by bioelectrical impedance analyzer in elderly population[J]. Medicine, 2020, 99(7):e19103

基金资助

江苏省自然科学基金(BK20230075)

江苏省卫生健康委医学科研重点项目(k2024057)