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Sinclair, A.J.;  Abdelhafiz, A.H. Effects of Multimorbidity and Frailty on Diabetes. Encyclopedia. Available online: (accessed on 09 December 2023).
Sinclair AJ,  Abdelhafiz AH. Effects of Multimorbidity and Frailty on Diabetes. Encyclopedia. Available at: Accessed December 09, 2023.
Sinclair, Alan J., Ahmed H. Abdelhafiz. "Effects of Multimorbidity and Frailty on Diabetes" Encyclopedia, (accessed December 09, 2023).
Sinclair, A.J., & Abdelhafiz, A.H.(2022, November 24). Effects of Multimorbidity and Frailty on Diabetes. In Encyclopedia.
Sinclair, Alan J. and Ahmed H. Abdelhafiz. "Effects of Multimorbidity and Frailty on Diabetes." Encyclopedia. Web. 24 November, 2022.
Effects of Multimorbidity and Frailty on Diabetes

Multimorbidity and frailty are highly prevalent in older people with diabetes. This high prevalence is likely due to a combination of ageing and diabetes-related complications and other diabetes-associated comorbidities. Both multimorbidity and frailty are associated with a wide range of adverse outcomes in older people with diabetes, which are proportionally related to the number of morbidities and to the severity of frailty.

older people diabetes multimorbidity frailty outcomes

1. Effects of Multimorbidity

Twelve studies investigated the association of multimorbidity and diabetes outcomes (Table 1). Heikkala et al., reported that multimorbidity was associated with achievement of glycaemic and LDL treatment targets. However, this was a cross-sectional study which did not reflect a cause-and effect relationship and the findings were just an indication that clinicians focused on patients with multimorbidity to achieve targets more than on patients with diabetes as a single disease [1]. Umeh et al., have shown that multimorbidity is associated with poor self-rated health in a proportionate manner and this association was unconnected to glycaemic control [2]. Certain multimorbidity combinations especially those that include depression, hypertension and arthritis increased the risk of disability in older people with diabetes as demonstrated by McClellan et al., while Coles B et al., in their large retrospective analysis found that, in addition to the level of multimorbidity, cardiovascular multimorbidity increased the risk of subsequent cardiovascular events, mortality and cardiovascular mortality [3][4]. However, the effect of multimorbidity on mortality may be affected by the ethnicity of the population studied. For example, data from the UK Biobank (a population predominantly of European origin), showed that a combination of coronary heart disease and heart failure, while the Taiwan National Diabetes Care Management Program (a population predominantly of Chinese ethnicity), showed that a combination of painful conditions and alcohol problems to be associated with the largest effect size on mortality, respectively. Although the UK cohort tended to have higher body weight than that of the Taiwanese cohort, which may increase their cardiovascular risk, {median (IQR) body mass index 30.8 (27.7, 34.8) kg/m2 vs. 25.6 (23.5, 28.7) kg/m2, there is still a need for further exploration of the effects of different patterns of multimorbidity on outcomes across different ethnic groups as suggested by Chiang et al. [5]. Increased risk of emergency department visits and hypoglycaemia-related hospitalisation are another multimorbidity-related outcomes which increases in proportion with the number of morbidities as demonstrated by McCoy et al. [6]. Another retrospective report by McCoy et al., demonstrated that HbA1c levels declined as the number of comorbidities increased reflecting clinical practice of tighter glycaemic control in multimorbid patients, rather than a direct relationship between multimorbidity and glycaemic control [7]. Similarly, Chiang et al., have demonstrated no association between multimorbidity and glycaemic control in their large cross-sectional general practice study [8]. Wong et al., found that health-related quality of life was impaired with increasing number of morbidities [9]. Mental health conditions such as depression, schizophrenia, substance use disorder and anxiety, which was present in 1 in 5 of older people with diabetes, was also associated with increased risk of mortality and hospital services use as reported by Guerrero Fernández de Alba et al. in their retrospective analysis [10]. Chiang el al, found no association between multimorbidity-related adverse outcomes and glycaemia markers such as HbA1c, glycaemic variability or time blood glucose in normal range suggesting that other factors, rather than dysglycaemia, contribute to the adverse outcomes associated with multimorbidity in older people with diabetes [11]. Among comorbidities, Quiñones et al., found that the presence of depressive symptoms or stroke, in particular, pose a substantial functional burden and contributed more to disabilities in ADL and IADL in older people with diabetes than other conditions [12].
Table 1. Recent studies exploring effects of multimorbidity on outcomes in older people with diabetes.

2. Effects of Frailty

Twelve studies investigated the association of frailty and diabetes outcomes (Table 2). Hanlon et al., analysed a large UK Biobank data (20,566 participants) using two frailty and two multimorbidity measures and found that each measure was associated with mortality, major adverse cardiovascular events (MACE), hypoglycaemia and fall or fracture [13]. Data from the Look AHEAD clinical trial showed that, after 8 years, the increases in frailty and multimorbidity were associated with poor cognitive function, physical function and increased mortality as reported by Espeland et al. [14]. Results From the ADVANCE trial showed that frailty predicted macro and microvascular events, all-cause mortality, cardiovascular mortality and hypoglycaemia as demonstrated by Nguyen et al., who concluded that frailty attenuated the benefits from blood pressure lowering and intensive glycaemic control [15]. In a retrospective analysis by Sable-Morita et al., frailty was a predictor of hospitalisations, institutional admissions, emergency outpatient visits, fractures, and mortality in older people with diabetes [16]. Ferri-Guerra et al., prospectively demonstrated association of frailty with all-cause hospitalisation and mortality independent of comorbidity [17]. Gual et al., investigated the impact of frailty on the outcome of a very old (≥80 years) cohort with diabetes and acute coronary syndrome. The association between diabetes and outcomes (incidence of death or readmission after 6 months) was not significant in robust patients, but it was significant in frail patients [18]. Among patients with diabetic kidney disease, frailty increased the risk of progression to end stage renal disease on a dose–response relationship and mortality, compared to those without frailty as reported by Chao et al. [19]. The prospective study by Kitamura et al., showed that all-cause mortality and disability in older people with mild diabetes were strongly affected by the presence of frailty [20]. Frailty was associated with low health related quality of life, depression, lean body mass and higher numbers of health-care visits in people with diabetes and chronic kidney disease as demonstrated in a cross-sectional analysis by Adame Perez et al. [21]. Chao et al., showed that both pre-frailty and frailty were associated with increased mortality, cardiovascular events, hospitalisation and health care utilisation [22]. In the community prospective study by Thein et al., frailty was associated with disability, which was potentiated by the presence of cognitive impairment. In addition, frailty, cognitive impairment or both were strong predictors of mortality [23]. In another community study by Li et al., frailty was associated with increased hospitalisation while both pre-frailty and frailty were associated with increased emergency department visits [24].
Table 2. Recent studies exploring effects of frailty on outcomes in older people with diabetes.


  1. Heikkala, E.; Mikkola, I.; Jokelainen, J.; Timonen, M.; Hagnäs, M. Multimorbidity and achievement of treatment goals among patients with type 2 diabetes: A primary care, real-world study. BMC Health Serv. Res. 2021, 21, 964.
  2. Umeh, K. Self-rated health and multimorbidity in patients with type 2 diabetes. J. Health Psychol. 2021, 27, 1659–1678.
  3. McClellan, S.P.; Haque, K.; García-Peña, C. Diabetes multimorbidity combinations and disability in the Mexican Health and Aging Study, 2012–2015. Arch. Gerontol. Geriatr. 2021, 93, 104292.
  4. Coles, B.; Zaccardi, F.; Hvid, C.; Davies, M.J.; Khunti, K. Cardiovascular events and mortality in people with type 2 diabetes and multimorbidity: A real-world study of patients followed for up to 19 years. Diabetes Obes. Metab. 2021, 23, 218–227.
  5. Chiang, J.I.; Hanlon, P.; Li, T.-C.; Jani, B.D.; Manski-Nankervis, J.-A.; Furler, J.; Lin, C.-C.; Yang, S.-Y.; Nicholl, B.I.; Thuraisingam, S.; et al. Multimorbidity, mortality, and HbA1c in type 2 diabetes: A cohort study with UK and Taiwanese cohorts. PLoS Med. 2020, 7, e1003094.
  6. McCoy, R.G.; Lipska, K.J.; Van Houten, H.K.; Shah, N.D. Association of Cumulative Multimorbidity, Glycemic Control, and Medication Use With Hypoglycemia-Related Emergency Department Visits and Hospitalizations Among Adults With Diabetes. JAMA Netw. Open 2020, 3, e1919099.
  7. McCoy, R.G.; Lipska, K.J.; Van Houten, H.K.; Shah, N.D. Paradox of glycemic management: Multimorbidity, glycemic control, and high-risk medication use among adults with diabetes. BMJ Open Diabetes Res. Care 2020, 8, e001007.
  8. Chiang, J.I.; Furler, J.; Mair, F.; Jani, B.D.; I Nicholl, B.; Thuraisingam, S.; Manski-Nankervis, J.-A. Associations between multimorbidity and glycaemia (HbA1c) in people with type 2 diabetes: Cross-sectional study in Australian general practice. BMJ Open 2020, 10, e039625.
  9. Wong, E.L.Y.; Xu, R.H.; Cheung, A.W.L. Measurement of health-related quality of life in patients with diabetes mellitus using EQ-5D-5L in Hong Kong, China. Qual. Life Res. 2020, 29, 1913–1921.
  10. Guerrero Fernández de Alba, I.; Gimeno-Miguel, A.; Poblador-Plou, B.; Gimeno-Feliu, L.A.; Ioakeim-Skoufa, I.; Rojo-Martínez, G.; Forjaz, M.J.; Prados-Torres, A. Association between mental health comorbidity and health outcomes in type 2 diabetes mellitus patients. Sci. Rep. 2020, 10, 19583.
  11. Chiang, J.I.; Manski-Nankervis, J.-A.; Thuraisingam, S.; Jenkins, A.; O’Neal, D.; Mair, F.S.; Jani, B.D.; Nicholl, B.I.; Furler, J. Multimorbidity, glycaemic variability and time in target range in people with type 2 diabetes: A baseline analysis of the GP-OSMOTIC trial. Diabetes Res. Clin. Pract. 2020, 169, 108451.
  12. Quiñones, A.R.; Markwardt, S.; Botoseneanu, A. Diabetes-Multimorbidity Combinations and Disability Among Middle-aged and Older Adults. J. Gen. Intern. Med. 2019, 34, 944–951.
  13. Hanlon, P.; Jani, B.D.; Butterly, E.; Nicholl, B.; Lewsey, J.; McAllister, D.A.; Mair, F.S. An analysis of frailty and multimorbidity in 20,566 UK Biobank participants with type 2 diabetes. Commun Med. 2021, 1, 28.
  14. Espeland, M.A.; Justice, J.N.; Bahnson, J.; Evans, J.K.; Munshi, M.; Hayden, K.M.; Simpson, F.R.; Johnson, K.C.; Johnston, C.; Kritchevsky, S.R. Look AHEAD Research Group. Eight Year Changes in Multimorbidity and Frailty in Adults with Type 2 Diabetes Mellitus: Associations with Cognitive and Physical Function and Mortality. J. Gerontol. A Biol. Sci. Med. Sci. 2021, 77, glab342.
  15. Nguyen, T.N.; Harris, K.; Woodward, M.; Chalmers, J.; Cooper, M.; Hamet, P.; Harrap, S.; Heller, S.; MacMahon, S.; Mancia, G.; et al. The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial. Diabetes Care 2021, 44, 1622–1629.
  16. Sable-Morita, S.; Tanikawa, T.; Satake, S.; Okura, M.; Tokuda, H.; Arai, H. Microvascular complications and frailty can predict adverse outcomes in older patients with diabetes. Geriatr. Gerontol. Int. 2021, 21, 359–363.
  17. Ferri-Guerra, J.; Aparicio-Ugarriza, R.; Salguero, D.; Baskaran, D.; Mohammed, Y.N.; Florez, H.; Ruiz, J.G. The Association of Frailty with Hospitalizations and Mortality among Community Dwelling Older Adults with Diabetes. J. Frailty Aging 2020, 9, 94–100.
  18. Gual, M.; Formiga, F.; Ariza-Solé, A.; López-Palop, R.; Sanchís, J.; Marín, F.; Vidán, M.T.; Martínez-Sellés, M.; Sionis, A.; Lorente, V.; et al. LONGEVO-SCA registry investigators. Diabetes mellitus, frailty and prognosis in very elderly patients with acute coronary syndromes. Aging Clin. Exp. Res. 2019, 31, 1635–1643.
  19. 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.
  20. Kitamura, A.; Taniguchi, Y.; Seino, S.; Yokoyama, Y.; Amano, H.; Fujiwara, Y.; Shinkai, S. Combined effect of diabetes and frailty on mortality and incident disability in older Japanese adults. Geriatr. Gerontol. Int. 2019, 19, 423–428.
  21. Perez, S.I.A.; 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.
  22. Chao, C.T.; Wang, J.; Chien, K.L.; COhort of GEriatric Nephrology in NTUH (COGENT) study group. Both pre-frailty and frailty increase healthcare utilization and adverse health outcomes in patients with type 2 diabetes mellitus. Cardiovasc. Diabetol. 2018, 17, 130.
  23. Thein, F.S.; Li, Y.; Nyunt, M.S.Z.; Gao, Q.; Wee, S.L.; Ng, T.P. Physical frailty and cognitive impairment is associated with diabetes and adversely impact functional status and mortality. Postgrad. Med. 2018, 130, 561–567.
  24. Li, C.L.; Stanaway, F.F.; Lin, J.D.; Chang, H.-Y. Frailty and health care use among community-dwelling older adults with diabetes: A population-based study. Clin. Interv. Aging 2018, 13, 2295–2300.
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