Objective To explore mediation effects of social status and lifestyle on the associations of diabetes and its traits with sarcopenia traits. Methods Mediation analysis was conducted to explore the potential social and lifestyle mediators of diabetes and its traits on sarcopenia traits [appendicular lean mass (ALM), hand grip strength (HGS), and walking pace (WP) ] in the National Health and Nutrition Examination Survey (NHANES). Mendelian randomization was performed to examine the causal associations based on summary-level data of the exposures, mediators, and outcomes derived from the public genome-wide studies. Results Based on NHANES data, diabetes was negatively associated with WP and HGS [β=-0.466, 95%CI (-0.562, -0.370), P=2.92×10-10], [β=-2.664, 95%CI (-3.645, -1.684), P=8.48×10-6], whereas no significant association was observed between diabetes and ALM (P>0.05), partly through factors like education, income, heavy physical activities and intakes of energy, carbohydrate, vitamin E and alcohol (indirect effect ranging from 2.96% to 73.11%). According to the Mendelian randomization analyses, diabetes was negatively associated with HGS [β=-0.275, 95%CI (-0.419, -0.130), P=2.04×10-4]. Additionally, diabetes related traits like paternal diabetes was negatively associated with HGS [β=-0.221, 95%CI (-0.377, -0.066), P=5.33×10-3], whereas sibling diabetes was negatively associated with HGS[β=-0.224, 95%CI (-0.377, -0.071), P=4.18×10-3 for right, [β=-0.293, 95%CI (-0.435, -0.151), P=5.21×10-5 for left], and WP[β=-0.275, 95%CI (-0.387, -0.164), P=1.33×10-6]. Income, light physical activities (PAs), intake frequency of dried fruit, salad and raw vegetable, intakes of red wine and spirits, played crucial roles as mediating factors in these associations (indirect effect ranging from 5.36% to 36.63%). Conclusion Income, PAs, alcohol consumption, and vegetable and fruit intakes play mediating roles in the relationships of diabetes and its traits with muscle health.
Key words
social-economic factor /
dietary intake /
exercise /
muscle health /
diabetes /
mediation study
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] CHEN LK, HSIAO F Y, AKISHITA M, et al.A focus shift from sarcopenia to muscle health in the Asian Working Group for Sarcopenia 2025 Consensus Update[J]. Nat Aging, 2025, 5(11): 2164-2175.
[2] YUAN S, LARSSON SC.Epidemiology of sarcopenia: prevalence, risk factors, and consequences[J]. Metabolism, 2023, 144: 155533.
[3] FENG L, GAO Q, HU K, et al.Prevalence and risk factors of sarcopenia in patients with diabetes: a meta-analysis[J]. J Clin Endocrinol Metab, 2022, 107(5): 1470-1483.
[4] CASTILLO ÍMP, ARGILÉS JM, RUEDA R, et al. Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: myocellular mechanisms involved[J]. Rev Endocr Metab Disord, 2025, 26(5): 815-836.
[5] GUERRA M, GARCIA D, DA COSTA DANIELE TM, et al. Associations between physical activity, socioeconomic and sociodemographic factors, and risk of sarcopenia in older adults in Northeast Brazil[J]. Bmc Public Health, 2025, 25(1): 3865.
[6] PARK JE, YANG N, KIM K.Dietary patterns associated with body-composition phenotype in a middle-aged and elderly population: a population-based cross-sectional study[J]. Nutrients, 2024, 16(21): 3583.
[7] MARTINO FK, ZATTARIN A, CINQUINI C, et al.Low-protein diet in elderly patients with chronic kidney disease stage 4 and 5 in conservative management: focus on sarcopenia development[J]. Nutrients, 2024, 16(10): 1498.
[8] ALCARÁZ N, SALCEDO-TELLO P, GONZÁLEZ-BARRIOS R, et al. Underlying mechanisms of the protective effects of lifestyle factors on age-related diseases[J]. Arch Med Res, 2024, 55(5): 103014.
[9] CHEN S, YAN S, AIHETI N, et al.A bi-directional Mendelian randomization study of sarcopenia-related traits and type 2 diabetes mellitus[J]. Front Endocrinol (Lausanne), 2023, 14: 1109800.
[10] WU Z, LEWIS E, ZHAO Q, et al.Causal mediation analysis for time-varying heritable risk factors with Mendelian randomization[J]. Nat Commun, 2025, 16(1): 6945.
[11] 王晋, 邹志, 刘棒, 等. 双样本孟德尔随机化法分析糖尿病对前列腺癌症的影响[J]. 湖南师范大学学报 (医学版), 2024, 21(5): 24-30.
[12] SANDERSON E.Multivariable Mendelian randomization and mediation[J]. Cold Spring Harb Perspect Med, 2021, 11(2): a038984.
[13] CHEN TC, CLARK J, RIDDLES MK, et al.National Health and Nutrition Examination Survey, 2015-2018: sample design and estimation procedures[J]. Vital Health Stat 2, 2020, (184): 1-35.
[14] BEŠEVIĆ J, SAID S, NAGY R, et al. UK Biobank: transforming drug discovery and precision medicine[J]. Br J Pharmacol, 2026, 183(2): 234-248.
[15] SUDLOW C, GALLACHER J, ALLEN N, et al.UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age[J]. PLoS Med, 2015, 12(3): e1001779.
[16] CHEN J, SPRACKLEN CN, MARENNE G, et al.The trans-ancestral genomic architecture of glycemic traits[J]. Nat Genet, 2021, 53(6): 840-860.
[17] LITTLE RR, ROHLFING C, SACKS DB.The National Glycohemoglobin Standardization Program: over 20 years of improving hemoglobin A1c measurement[J]. Clin Chem, 2019, 65(7): 839-848.
[18] LEE JJ, WEDOW R, OKBAY A, et al.Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals[J]. Nat Genet, 2018, 50(8): 1112-1121.
[19] CLARKE TK, ADAMS MJ, DAVIES G, et al.Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)[J]. Mol Psychiatry, 2017, 22(10): 1376-1384.
[20] CRUZ-JENTOFT AJ, BAHAT G, BAUER J, et al.Sarcopenia: revised European consensus on definition and diagnosis[J]. Age Ageing, 2019, 48(1): 16-31.
[21] PEI YF, LIU YZ, YANG XL, et al.The genetic architecture of appendicular lean mass characterized by association analysis in the UK Biobank study[J]. Commun Biol, 2020, 3(1): 608.
[22] JONES G, TRAJANOSKA K, SANTANASTO AJ, et al.Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women[J]. Nat Commun, 2021, 12(1): 654.
[23] HEMANI G, ZHENG J, ELSWORTH B, et al.The MR-Base platform supports systematic causal inference across the human phenome[J]. Elife, 2018, 7: e34408.
[24] DAVIES NM, HOLMES MV, DAVEY SMITH G.Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians[J]. BMJ, 2018, 362: k601.
[25] BURGESS S, DAVEY SMITH G, DAVIES NM, et al.Guidelines for performing Mendelian randomization investigations: update for summer 2023[J]. Wellcome Open Res, 2023, 4: 186.
[26] CARTER AR, SANDERSON E, HAMMERTON G, et al.Mendelian randomisation for mediation analysis: current methods and challenges for implementation[J]. Eur J Epidemiol, 2021, 36(5): 465-478.
[27] BURGESS S, THOMPSON SG.Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects[J]. Am J Epidemiol, 2015, 181(4): 251-260.
[28] BURGESS S, DANIEL RM, BUTTERWORTH AS, et al.Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways[J]. Int J Epidemiol, 2015, 44(2): 484-495.
[29] BOWDEN J, SMITH GD, HAYCOCK PC, et al.Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator[J]. Genet Epidemiol, 2016, 40(4): 304-314.
[30] BURGESS S, THOMPSON SG.Interpreting findings from Mendelian randomization using the MR-Egger method[J]. Eur J Epidemiol, 2017, 32(5): 377-389.
[31] VERBANCK M, CHEN CY, NEALE B, et al.Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J]. Nat Genet, 2018, 50(5): 693-698.
[32] BURGESS S, BOWDEN J, FALL T, et al.Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants[J]. Epidemiology, 2017, 28(1): 30-42.
[33] ZHAO Q, WANG J, HEMANI G, et al.Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score[J]. Ann Stat, 2020, 48(3): 1742-1769.
[34] GILL D.Heterogeneity between genetic variants as a proxy for pleiotropy in Mendelian randomization[J]. JAMA Cardiol, 2020, 5(1): 107-108.
[35] RELTON CL, DAVEY SMITH G.Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease[J]. Int J Epidemiol, 2012, 41(1): 161-176.
[36] QIAO YS, CHAI YH, GONG HJ, et al.The association between diabetes mellitus and risk of sarcopenia: accumulated evidences from observational studies[J]. Front Endocrinol (Lausanne), 2021, 12: 782391.
[37] PEDRON S, KURZ CF, SCHWETTMANN L, et al.The effect of BMI and type 2 diabetes on socioeconomic status: a two-sample multivariable Mendelian randomization study[J]. Diabetes Care, 2021, 44(3): 850-852.
[38] DARVISHI A, NIKKHAH A, MAHMUDIMANESH M, et al.Socioeconomic inequalities in type 2 diabetes mellitus: a study based on a population-based survey in Iran[J]. BMC Public Health, 2024, 24(1): 926.
[39] CHEVAL B, MALTAGLIATI S, SIEBER S, et al.Why are individuals with diabetes less active? The mediating role of physical, emotional, and cognitive factors[J]. Ann Behav Med, 2021, 55(9): 904-917.
[40] QIU B, ZHOU Y, TAO X, et al.The effect of exercise on flow-mediated dilation in people with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials[J]. Front Endocrinol (Lausanne), 2024, 15: 1347399.
[41] SIMON L, BOURGEOIS BL, MOLINA PE.Alcohol and skeletal muscle in health and disease[J]. Alcohol Res, 2023, 43(1): 04.
[42] RODRÍGUEZ-GRACIANI KM, MOLINA PE, SIMON L. Alcohol-mediated skeletal muscle adaptations and their impact on comorbidities[J]. Am J Pathol, 2026, 196(1): 92-103.
[43] HAHM JH, NIRMALA F, HA TY, et al.Nutritional approaches targeting mitochondria for the prevention of sarcopenia[J]. Nutr Rev, 2024, 82(5): 676-694.
[44] LI J, FONG DYT, LOK KYW, et al.Key lifestyles and health outcomes across 16 prevalent chronic diseases: A network analysis of an international observational study[J]. J Glob Health, 2024, 14: 04068.
[45] BAROUTI AA, TYNELIUS P, LAGER A, et al.Fruit and vegetable intake and risk of prediabetes and type 2 diabetes: results from a 20-year long prospective cohort study in Swedish men and women[J]. Eur J Nutr, 2022, 61(6): 3175-3187.
[46] STANAWAY JD, AFSHIN A, ASHBAUGH C, et al.Health effects associated with vegetable consumption: a burden of proof study[J]. Nat Med, 2022, 28(10): 2066-2074.
[47] 冷朝会, 海珊, 陈龄, 等. 生活方式对肌少症影响的研究进展[J]. 中国疗养医学, 2023, 32(8): 811-814.
PDF(2215 KB)
