The frailty risk trajectory associated with kidney and cardiovascular morbidities among patients with incident diabetes: A population-based study

  • Jui Wang
    Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
    Search for articles by this author
  • Szu-Ying Lee
    Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan
    Search for articles by this author
  • Chia-Ter Chao
    Corresponding author. National Taiwan University Hospital, Taipei, Taiwan.
    Neprology Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan
    Search for articles by this author
  • Jenq-Wen Huang
    Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan

    Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
    Search for articles by this author
  • Kuo-Liong Chien
    Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
    Search for articles by this author


      • Patients with diabetes mellitus or chronic kidney disease are at risk of frailty.
      • Diabetes predisposes patients to developing cardiovascular morbidities.
      • The influences of CKD or CV morbidities on the course of frailty in diabetic patients remains unclear.
      • Our findings illustrate the effect of CKD and CV morbidities on incident frailty risk.
      • Comorbidities-oriented care strategies potentially reduce frailty risk in these patients.


      Background and aims

      Frailty denotes the increased vulnerability to stressors/insults associated with aging or diseases, and has high incidence in patients with diabetes mellitus (DM). We hypothesized that chronic kidney disease (CKD) and non-kidney morbidities in patients with newly diagnosed DM might modulate their risk of developing incident frailty.


      From the Longitudinal Cohort of Diabetes Patients, we identified 322,109 patients with newly diagnosed DM, and classified them into those without CKD, with CKD before and after DM. We used Kaplan-Meier analyses and Cox proportional hazard regression to analyze associations between CKD or non-kidney morbidities and the risk of incident frailty. We further analyzed the year-to-year trend of frailty risk brought by CKD or non-kidney morbidities.


      Patients with DM but without CKD (n = 249,752; 77.5%), with CKD prior to (n = 23,829; 7.4%), and after DM (n = 48,528; 15.1%) were enrolled. Those with CKD, regardless of onset timing, had a significantly higher risk of developing frailty than those without (for onset prior to DM, hazard ratio (HR) 1.235, 95% confidence interval (CI) 1.11–1.38; for onset after DM, HR 1.386, 95% CI 1.21–1.59). The risk was more prominent early after the diagnosis of DM was made. Patients with chronic obstructive pulmonary disease, liver, and cardiovascular morbidities all had a significantly higher risk of frailty than those without, with cerebrovascular accident carrying the most prominent risk elevation (HR 4.059, 95% CI 3.73–4.42).


      CKD regardless of onset timing relative to DM predicted a higher risk of incident frailty, while non-kidney morbidities including cardiovascular morbidities, similarly increased frailty risk among incident diabetic patients.

      Graphical abstract


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Walston J.
        • Hadley E.C.
        • Ferrucci L.
        • et al.
        Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American geriatrics society/national institute on aging research conference on frailty in older adults.
        J. Am. Geriatr. Soc. 2006; 54: 991-1001
        • Ekram A.
        • Woods R.L.
        • Britt C.
        • Espinoza S.
        • Ernst M.E.
        • Ryan J.
        The association between frailty and all-cause mortality in community-dwelling older individuals: an umbrella review.
        J. Frailty Aging. 2021; 10: 320-326
        • Cunha A.I.L.
        • Veronese N.
        • de Melo Borges S.
        • Ricci N.A.
        Frailty as a predictor of adverse outcomes in hospitalized older adults: a systematic review and meta-analysis.
        Ageing Res. Rev. 2019; 56100960
        • Chi J.
        • Chen F.
        • Zhang J.
        • et al.
        Impacts of frailty on health care costs among community-dwelling older adults: a meta-analysis of cohort studies.
        Arch. Gerontol. Geriatr. 2021; 94104344
        • Collard R.M.
        • Boter H.
        • Schoevers R.A.
        • Oude Voshaar R.C.
        Prevalence of frailty in community-dwelling older persons: a systematic review.
        J. Am. Geriatr. Soc. 2012; 60: 1487-1492
        • Dent E.
        • Morley J.E.
        • Cruz-Jentoft A.J.
        • et al.
        Physical frailty: ICFSR international clinical practice guidelines for identification and management.
        J. Nutr. Health Aging. 2019; 23: 771-787
        • Wang J.
        • Maxwell C.A.
        • Yu F.
        Biological processes and biomarkers related to frailty in older adults: a state-of-the-science literature review.
        Biol. Res. Nurs. 2019; 21: 80-106
        • Kong L.N.
        • Lyu Q.
        • Yao H.Y.
        • Yang L.
        • Chen S.Z.
        The prevalence of frailty among community-dwelling older adults with diabetes: a meta-analysis.
        Int. J. Nurs. Stud. 2021; 119103952
        • Assar M.E.
        • Laosa O.
        • Rodríguez Mañas L.
        Diabetes and frailty.
        Curr. Opin. Clin. Nutr. Metab. Care. 2019; 22: 52-57
        • Wu P.Y.
        • Chao C.T.
        • Chan D.C.
        • Huang J.W.
        • Hung K.Y.
        Contributors, risk associates, and complications of frailty in patients with chronic kidney disease: a scoping review.
        Ther. Adv. Chronic Dis. 2019; 102040622319880382
        • Takeuchi H.
        • Uchida H.A.
        • Kakio Y.
        • et al.
        The prevalence of frailty and its associated factors in Japanese hemodialysis patients.
        Aging Dis. 2018; 9: 192-207
        • Chao C.T.
        • Lee S.Y.
        • Wang J.
        • Chien K.L.
        • Hung K.Y.
        The risk trajectory of different cardiovascular morbidities associated with chronic kidney disease among patients with newly diagnosed diabetes mellitus: a propensity score-matched cohort analysis.
        Cardiovasc. Diabetol. 2021; 20: 86
        • Chao C.T.
        • Wang J.
        • Chien K.L.
        Both pre-frailty and frailty increase healthcare utilization and adverse health outcomes in patients with type 2 diabetes mellitus.
        Cardiovasc. Diabetol. 2018; 17: 130
        • Chao C.T.
        • Wang J.
        • Huang J.W.
        • Chan D.C.
        • Chien K.L.
        Frailty predicts an increased risk of end-stage renal disease with risk competition by mortality among 165,461 diabetic kidney disease patients.
        Aging Dis. 2019; 10: 1270-1281
        • Lee S.Y.
        • Wang J.
        • Chao C.T.
        • Chien K.L.
        • Huang J.W.
        Frailty modifies the association between opioid use and mortality in chronic kidney disease patients with diabetes: a population-based cohort study.
        Aging (Albany NY). 2020; 12: 21730-21746
        • Chao C.T.
        • Lee S.Y.
        • Wang J.
        • Chien K.L.
        • Huang J.W.
        Frailty increases the risk for developing urinary tract infection among 79,887 patients with diabetic mellitus and chronic kidney disease.
        BMC Geriatr. 2021; 21: 349
        • Wu V.C.
        • Wu C.H.
        • Huang T.M.
        • et al.
        Long-term risk of coronary events after AKI.
        J. Am. Soc. Nephrol. 2014; 25: 595-605
        • Kramer H.
        Screening for kidney disease in adults with diabetes and prediabetes.
        Curr. Opin. Nephrol. Hypertens. 2005; 14: 249-252
        • Chang H.Y.
        • Weiner J.P.
        • Richards T.M.
        • Bleich S.N.
        • Segal J.B.
        Validating the adapted diabetes complications severity index in claims data.
        Am. J. Manag. Care. 2012; 18: 721-726
        • Wicke F.S.
        • Glushan A.
        • Schubert I.
        • et al.
        Performance of the adpated diabetes complications severity index translated to ICD-10.
        Am. J. Manag. Care. 2019; 25: e45-e49
        • McElvany M.D.
        • Chan P.H.
        • Prentice H.A.
        • Paxton E.W.
        • Dillon M.T.
        • Navarro R.A.
        Diabetes disease severity was not associated with risk of deep infection or revision after shoulder arthroplasty.
        Clin. Orthop. Relat. Res. 2019; 477: 1358-1369
        • Li Y.
        • Zou Y.
        • Wang S.
        • et al.
        A pilot study of the FRAIL scale on predicting outcomes in Chinese elderly people with type 2 diabetes.
        J. Am. Med. Dir. Assoc. 2015; 16 (e7-.e12): 714
        • Adame Perez S.I.
        • Senior P.A.
        • Field C.J.
        • Jindal K.
        • Mager D.R.
        Frailty, health-related quality of life, cognition, depression, vitamin D and health-care utilization in an ambulatory adult population with type 1 or type 2 diabetes mellitus and chronic kidney disease: a cross-sectional analysis.
        Can. J. Diabetes. 2019; 43: 90-97
        • Lee S.Y.
        • Wang J.
        • Tsai H.B.
        • Chao C.T.
        • Chien K.L.
        • Huang J.W.
        Muscle relaxant use and the associated risk of incident frailty in patients with diabetic kidney disease: a longitudinal cohort study.
        Ther. Adv. Drug Saf. 2021; 1220420986211014639
        • Abellan van Kan G.
        • Rolland Y.
        • Bergman H.
        • Morley J.E.
        • Kritchevsky S.B.
        • Vellas B.
        The I.A.N.A Task Force on frailty assessment of older people in clinical practice.
        J. Nutr. Health Aging. 2008; 12: 29-37
        • Lee S.Y.
        • Wang J.
        • Chao C.T.
        • Chien K.L.
        • Huang J.W.
        Frailty is associated with a higher risk of developing delirium and cognitive impairment among patients with diabetic kidney disease: a longitudinal population-based cohort study.
        Diabet. Med. 2021; 38e14566
        • Lorenz E.C.
        • Kennedy C.C.
        • Rule A.D.
        • LeBrasseur N.K.
        • kirkland J.L.
        • Hickson L.J.
        Frailty in CKD and transplantion.
        Kidney Int. Rep. 2021; 6: 2270-2280
        • Buta B.
        • Choudhury P.P.
        • Xue Q.L.
        • et al.
        The association of vitamin D deficiency and incident frailty in older women: the role of cardiometabolic diseases.
        J. Am. Geriatr. Soc. 2017; 65: 619-624
        • Calderon-Larranaga A.
        • Vetrano D.L.
        • Ferrucci L.
        • et al.
        Multimorbidity and functional impairment – bidirectional interplay, synergistic effects and common pathways.
        J. Intern. Med. 2019; 285: 255-271
        • Wu H.
        • Lau E.S.H.
        • Yang A.
        • et al.
        Young age at diabetes diagnosis amplifies the effect of diabetes duration on risk of chronic kidney disease: a prospective cohort study.
        Diabetologia. 2021; 64: 1990-2000
        • Çakmak G.
        • Ganidağlı S.
        • Efendioğlu E.M.
        • Öztürk E.
        • Öztürk Z.A.
        Do long-term complications of type 2 diabetes increase susceptibility to geriatric syndromes in older adults?.
        Medicina (Kaunas). 2021; 57: 968
        • Ida S.
        • Kaneko R.
        • Imataka K.
        • Fujiwara R.
        • Murata K.
        Are diabetes-related factors associated with the social roles of elderly patients with diabetes?.
        J. Diabet. Complicat. 2021; 35107759
        • kwok C.S.
        • Lundberg G.
        • Al-Faleh H.
        • et al.
        Relation of frailty to outcomes in patients with acute coronary syndromes.
        Am. J. Cardiol. 2019; 124: 1002-1011
        • Yong P.S.A.A.
        • Sim E.Y.L.
        • Ho C.Y.X.
        • et al.
        Association of multimorbidity with frailty in older adults for elective non-cardiac surgey.
        Cureus. 2021; 13e15033
        • Proietti M.
        • Cesari M.
        Describing the relationship between atrial fibrillation and frailty: clinical implications and open research questions.
        Exp. Gerontol. 2021; 152111455
        • Pandey A.
        • kitzman D.
        • Reeves G.
        Frailty is intertwined with heart failure: mechanisms, prevalence, prognosis, assessment, and management.
        JACC Heart Fail. 2019; 7: 1001-1011
        • Chunawala Z.S.
        • Qamar A.
        • Arora S.
        • et al.
        Prevalence and prognostic significance of polyvascular disease in patients hospitalized with acute decompensated heart failure: the ARIC study.
        J. Card. Fail. 2022; : S1071-S9164
        • Tamura Y.
        • Omura T.
        • Toyoshima K.
        • Araki A.
        Nutrition management in older adults with diabetes: a review on the importance of shifting prevention strategies from metabolic syndrome to frailty.
        Nutrients. 2020; 12: 3367
        • Vigorito C.
        • Abreu A.
        • Ambrosetti M.
        • et al.
        Frailty and cardiac rehabilitation: a call to action from the EAPC Cardiac Rehabilitation Section.
        Eur. J. Prev. Cardiol. 2017; 24: 577-590