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Published in: Cardiovascular Diabetology 1/2019

Open Access 01-12-2019 | Original investigation

Relationship between frailty and mortality, hospitalization, and cardiovascular diseases in diabetes: a systematic review and meta-analysis

Authors: Satoshi Ida, Ryutaro Kaneko, Kanako Imataka, Kazuya Murata

Published in: Cardiovascular Diabetology | Issue 1/2019

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Abstract

Background

In patients with diabetes, death and cardiovascular diseases are attributed to classical risk factors such as hypertension, dyslipidemia, and smoking habit, whereas these events are attributed to frailty in the remaining patients. In this meta-analysis, we examined the relationship between frailty and mortality, hospitalization, and cardiovascular diseases in patients with diabetes.

Methods

Literature search was conducted using databases such as MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. Studies that examined the relationship between frailty and mortality, hospitalization, and cardiovascular disease and included hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were included. Statistical analysis was performed using a random effects model, and pooled HRs, pooled ORs, and 95% CIs were calculated.

Results

The literature search extracted 8 studies (565,039 patients) that met our inclusion criteria, which were included in this meta-analysis. The pooled HR of prefrailty and frailty related to mortality was 1.09 (95% CI 1.01–1.17; P = 0.02) and 1.35 (95% CI 1.05–1.74; P = 0.02), respectively, indicating a significant relationship between them. The pooled OR of prefrailty and frailty related to hospitalization was 2.15 (95% CI 1.30–3.54; P = 0.003) and 5.18 (95% CI 2.68–9.99; P < 0.001), respectively, indicating a significant relationship. Although a significant relationship was found between frailty and cardiovascular diseases, we found only few related studies; thus, robust results could not be obtained.

Conclusions

In patients with diabetes, a significant relationship was observed between frailty and mortality and hospitalization. However, only few heterogeneous studies were included, warranting further examination.
Literature
1.
go back to reference King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21:1414–31.CrossRef King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21:1414–31.CrossRef
2.
go back to reference Zimmet PZ. Diabetes epidemiology as a tool to trigger diabetes research and care. Diabetologia. 1999;42:499–518.CrossRef Zimmet PZ. Diabetes epidemiology as a tool to trigger diabetes research and care. Diabetologia. 1999;42:499–518.CrossRef
3.
go back to reference Araki E, Haneda M, Kasuga M, Nishikawa T, Kondo T, Ueki K, et al. New glycemic targets for patients with diabetes from the Japan Diabetes Society. J Diabetes Investig. 2017;8:123–5.CrossRef Araki E, Haneda M, Kasuga M, Nishikawa T, Kondo T, Ueki K, et al. New glycemic targets for patients with diabetes from the Japan Diabetes Society. J Diabetes Investig. 2017;8:123–5.CrossRef
4.
go back to reference Mohammedi K, Woodward M, Marre M, Colagiuri S, Cooper M, Harrap S, et al. Comparative effects of microvascular and macrovascular disease on the risk of major outcomes in patients with type 2 diabetes. Cardiovasc Diabetol. 2017;16:95.CrossRef Mohammedi K, Woodward M, Marre M, Colagiuri S, Cooper M, Harrap S, et al. Comparative effects of microvascular and macrovascular disease on the risk of major outcomes in patients with type 2 diabetes. Cardiovasc Diabetol. 2017;16:95.CrossRef
5.
go back to reference Quilliam BJ, Simeone JC, Ozbay AB, Kogut SJ. The incidence and costs of hypoglycemia in type 2 diabetes. Am J Manag Care. 2011;17:673–80.PubMed Quilliam BJ, Simeone JC, Ozbay AB, Kogut SJ. The incidence and costs of hypoglycemia in type 2 diabetes. Am J Manag Care. 2011;17:673–80.PubMed
6.
go back to reference Chen HL, Hsu WW, Hsiao FY. Changes in prevalence of diabetic complications and associated healthcare costs during a 10-year follow-up period among a nationwide diabetic cohort. J Diabetes Complications. 2015;29:523–8.CrossRef Chen HL, Hsu WW, Hsiao FY. Changes in prevalence of diabetic complications and associated healthcare costs during a 10-year follow-up period among a nationwide diabetic cohort. J Diabetes Complications. 2015;29:523–8.CrossRef
7.
go back to reference Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381:752–62.CrossRef Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381:752–62.CrossRef
8.
go back to reference Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.CrossRef Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.CrossRef
9.
go back to reference Morley JE, Malmstrom TK, Rodriguez-Manas L, Sinclair AJ. Frailty, sarcopenia and diabetes. J Am Med Dir Assoc. 2014;15:853–9.CrossRef Morley JE, Malmstrom TK, Rodriguez-Manas L, Sinclair AJ. Frailty, sarcopenia and diabetes. J Am Med Dir Assoc. 2014;15:853–9.CrossRef
10.
go back to reference Saum KU, Dieffenbach AK, Muller H, Holleczek B, Hauer K, Brenner H. Frailty prevalence and 10-year survival in community-dwelling older adults: results from the ESTHER cohort study. Eur J Epidemiol. 2014;29:171–9.CrossRef Saum KU, Dieffenbach AK, Muller H, Holleczek B, Hauer K, Brenner H. Frailty prevalence and 10-year survival in community-dwelling older adults: results from the ESTHER cohort study. Eur J Epidemiol. 2014;29:171–9.CrossRef
11.
go back to reference Ottenbacher KJ, Graham JE, Al Snih S, Raji M, Samper-Ternent R, Ostir GV, et al. Mexican Americans and frailty: findings from the Hispanic established populations epidemiologic studies of the elderly. Am J Public Health. 2009;99:673–9.CrossRef Ottenbacher KJ, Graham JE, Al Snih S, Raji M, Samper-Ternent R, Ostir GV, et al. Mexican Americans and frailty: findings from the Hispanic established populations epidemiologic studies of the elderly. Am J Public Health. 2009;99:673–9.CrossRef
12.
go back to reference Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol. 2014;2:819–29.CrossRef Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol. 2014;2:819–29.CrossRef
13.
go back to reference Chen LK, Chen YM, Lin MH, Peng LN, Hwang SJ. Care of elderly patients with diabetes mellitus: a focus on frailty. Ageing Res Rev. 2010;9:S18–22.CrossRef Chen LK, Chen YM, Lin MH, Peng LN, Hwang SJ. Care of elderly patients with diabetes mellitus: a focus on frailty. Ageing Res Rev. 2010;9:S18–22.CrossRef
14.
go back to reference Regidor E, Franch J, Segui M, Serrano R, Rodriguez-Artalejo F, Artola S. Traditional risk factors alone could not explain the excess mortality in patients with diabetes: a national cohort study of older Spanish adults. Diabetes Care. 2012;35:2503–9.CrossRef Regidor E, Franch J, Segui M, Serrano R, Rodriguez-Artalejo F, Artola S. Traditional risk factors alone could not explain the excess mortality in patients with diabetes: a national cohort study of older Spanish adults. Diabetes Care. 2012;35:2503–9.CrossRef
15.
go back to reference Volpato S, Blaum C, Resnick H, Ferrucci L, Fried LP, Guralnik JM, et al. Comorbidities and impairments explaining the association between diabetes and lower extremity disability: The Women’s Health and Aging Study. Diabetes Care. 2002;25:678–83.CrossRef Volpato S, Blaum C, Resnick H, Ferrucci L, Fried LP, Guralnik JM, et al. Comorbidities and impairments explaining the association between diabetes and lower extremity disability: The Women’s Health and Aging Study. Diabetes Care. 2002;25:678–83.CrossRef
16.
go back to reference Palmas W, Pickering TG, Teresi J, Schwartz JE, Moran A, Weinstock RS, et al. Ambulatory blood pressure monitoring and all-cause mortality in elderly people with diabetes mellitus. Hypertension. 2009;53:120–7.CrossRef Palmas W, Pickering TG, Teresi J, Schwartz JE, Moran A, Weinstock RS, et al. Ambulatory blood pressure monitoring and all-cause mortality in elderly people with diabetes mellitus. Hypertension. 2009;53:120–7.CrossRef
17.
go back to reference Kojima G. Frailty as a predictor of hospitalisation among community-dwelling older people: a systematic review and meta-analysis. J Epidemiol Community Health. 2016;70:722–9.CrossRef Kojima G. Frailty as a predictor of hospitalisation among community-dwelling older people: a systematic review and meta-analysis. J Epidemiol Community Health. 2016;70:722–9.CrossRef
18.
go back to reference Hajek A, Bock JO, Saum KU, Matschinger H, Brenner H, Holleczek B, et al. Frailty and healthcare costs-longitudinal results of a prospective cohort study. Age Ageing. 2018;47:233–41.CrossRef Hajek A, Bock JO, Saum KU, Matschinger H, Brenner H, Holleczek B, et al. Frailty and healthcare costs-longitudinal results of a prospective cohort study. Age Ageing. 2018;47:233–41.CrossRef
19.
go back to reference Morley JE. Nutritional supplementation and sarcopenia: the evidence grows. J Am Med Dir Assoc. 2015;16:717–9.CrossRef Morley JE. Nutritional supplementation and sarcopenia: the evidence grows. J Am Med Dir Assoc. 2015;16:717–9.CrossRef
20.
go back to reference Theou O, Stathokostas L, Roland KP, Jakobi JM, Patterson C, Vandervoort AA, et al. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res. 2011;2011:569194.CrossRef Theou O, Stathokostas L, Roland KP, Jakobi JM, Patterson C, Vandervoort AA, et al. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res. 2011;2011:569194.CrossRef
21.
go back to reference Cadore EL, Izquierdo M. Exercise interventions in poly pathological aging patients that coexist with diabetes mellitus: improving functional status and quality of life. Age. 2015;37:64.CrossRef Cadore EL, Izquierdo M. Exercise interventions in poly pathological aging patients that coexist with diabetes mellitus: improving functional status and quality of life. Age. 2015;37:64.CrossRef
22.
go back to reference Kim SY, Park JE, Lee YJ, Seo HJ, Sheen SS, Hahn S, et al. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol. 2013;66:408–14.CrossRef Kim SY, Park JE, Lee YJ, Seo HJ, Sheen SS, Hahn S, et al. Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity. J Clin Epidemiol. 2013;66:408–14.CrossRef
23.
go back to reference Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRef Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRef
25.
go back to reference Cacciatore F, Testa G, Galizia G, Della-Morte D, Mazzella F, Langellotto A, et al. Clinical frailty and long-term mortality in elderly subjects with diabetes. Acta Diabetol. 2013;50:251–60.CrossRef Cacciatore F, Testa G, Galizia G, Della-Morte D, Mazzella F, Langellotto A, et al. Clinical frailty and long-term mortality in elderly subjects with diabetes. Acta Diabetol. 2013;50:251–60.CrossRef
26.
go back to reference Wang CP, Lorenzo C, Espinoza SE. Frailty attenuates the impact of metformin on reducing mortality in older adults with type 2 diabetes. J Endocrinol Diabetes Obes. 2014;2(2):1031.PubMedPubMedCentral Wang CP, Lorenzo C, Espinoza SE. Frailty attenuates the impact of metformin on reducing mortality in older adults with type 2 diabetes. J Endocrinol Diabetes Obes. 2014;2(2):1031.PubMedPubMedCentral
27.
go back to reference Li Y, Zou Y, Wang S, Li J, Jing X, Yang M, 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(714):e7–12. Li Y, Zou Y, Wang S, Li J, Jing X, Yang M, 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(714):e7–12.
28.
go back to reference Castro-Rodriguez M, Carnicero JA, Garcia-Garcia FJ, Walter S, Morley JE, Rodriguez-Artalejo F, et al. Frailty as a major factor in the increased risk of death and disability in older people with diabetes. J Am Med Dir Assoc. 2016;17:949–55.CrossRef Castro-Rodriguez M, Carnicero JA, Garcia-Garcia FJ, Walter S, Morley JE, Rodriguez-Artalejo F, et al. Frailty as a major factor in the increased risk of death and disability in older people with diabetes. J Am Med Dir Assoc. 2016;17:949–55.CrossRef
29.
go back to reference Chode S, Malmstrom TK, Miller DK, Morley JE. Frailty, diabetes, and mortality in middle-aged African Americans. J Nutr Health Aging. 2016;20:854–9.CrossRef Chode S, Malmstrom TK, Miller DK, Morley JE. Frailty, diabetes, and mortality in middle-aged African Americans. J Nutr Health Aging. 2016;20:854–9.CrossRef
30.
go back to reference Liccini A, Malmstrom TK. Frailty and sarcopenia as predictors of adverse health outcomes in persons with diabetes mellitus. J Am Med Dir Assoc. 2016;17:846–51.CrossRef Liccini A, Malmstrom TK. Frailty and sarcopenia as predictors of adverse health outcomes in persons with diabetes mellitus. J Am Med Dir Assoc. 2016;17:846–51.CrossRef
31.
go back to reference Chao CT, Wang J, Chien KL, 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.CrossRef Chao CT, Wang J, Chien KL, 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.CrossRef
32.
go back to reference Li CL, Stanaway FF, Lin JD, Chang HY. Frailty and health care use among community-dwelling older adults with diabetes: a population-based study. Clin Interv Aging. 2018;13:2295–300.CrossRef Li CL, Stanaway FF, Lin JD, Chang HY. Frailty and health care use among community-dwelling older adults with diabetes: a population-based study. Clin Interv Aging. 2018;13:2295–300.CrossRef
33.
go back to reference Kojima G. Frailty Defined by FRAIL Scale as a predictor of mortality: a systematic review and meta-analysis. J Am Med Dir Assoc. 2018;19:480–3.CrossRef Kojima G. Frailty Defined by FRAIL Scale as a predictor of mortality: a systematic review and meta-analysis. J Am Med Dir Assoc. 2018;19:480–3.CrossRef
34.
go back to reference Vermeiren S, Vella-Azzopardi R, Beckwee D, Habbig AK, Scafoglieri A, Jansen B, et al. Frailty and the prediction of negative health outcomes: a meta-analysis. J Am Med Dir Assoc. 2016;17(1163):e1–17. Vermeiren S, Vella-Azzopardi R, Beckwee D, Habbig AK, Scafoglieri A, Jansen B, et al. Frailty and the prediction of negative health outcomes: a meta-analysis. J Am Med Dir Assoc. 2016;17(1163):e1–17.
35.
go back to reference de Miguel-Yanes JM, Jiménez-García R, Hernández-Barrera V, Méndez-Bailón M, de Miguel-Díez J, Lopez-de-Andrés A. Impact of type 2 diabetes mellitus on in-hospital-mortality after major cardiovascular events in Spain (2002–2014). Cardiovasc Diabetol. 2017;16:126.CrossRef de Miguel-Yanes JM, Jiménez-García R, Hernández-Barrera V, Méndez-Bailón M, de Miguel-Díez J, Lopez-de-Andrés A. Impact of type 2 diabetes mellitus on in-hospital-mortality after major cardiovascular events in Spain (2002–2014). Cardiovasc Diabetol. 2017;16:126.CrossRef
36.
go back to reference Kosiborod M, Gomes MB, Nicolucci A, Pocock S, Rathmann W, Shestakova MV, et al. Vascular complications in patients with type 2 diabetes: prevalence and associated factors in 38 countries (the DISCOVER study program). Cardiovasc Diabetol. 2018;17:150.CrossRef Kosiborod M, Gomes MB, Nicolucci A, Pocock S, Rathmann W, Shestakova MV, et al. Vascular complications in patients with type 2 diabetes: prevalence and associated factors in 38 countries (the DISCOVER study program). Cardiovasc Diabetol. 2018;17:150.CrossRef
37.
go back to reference Kiss Z, Rokszin G, Abonyi-Toth Z, Jermendy G, Kempler P, Aradi D, et al. Dissimilar impact of type 2 diabetes on cardiovascular outcomes according to age categories: a nationwide population study from Hungary. Cardiovasc Diabetol. 2018;17:107.CrossRef Kiss Z, Rokszin G, Abonyi-Toth Z, Jermendy G, Kempler P, Aradi D, et al. Dissimilar impact of type 2 diabetes on cardiovascular outcomes according to age categories: a nationwide population study from Hungary. Cardiovasc Diabetol. 2018;17:107.CrossRef
38.
go back to reference Veronese N, Cereda E, Stubbs B, Solmi M, Luchini C, Manzato E, et al. Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: results from a meta-analysis and exploratory meta-regression analysis. Ageing Res Rev. 2017;35:63–73.CrossRef Veronese N, Cereda E, Stubbs B, Solmi M, Luchini C, Manzato E, et al. Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: results from a meta-analysis and exploratory meta-regression analysis. Ageing Res Rev. 2017;35:63–73.CrossRef
39.
go back to reference Abdelhafiz AH, Rodriguez-Manas L, Morley JE, Sinclair AJ. Hypoglycemia in older people—a less well recognized risk factor for frailty. Aging Dis. 2015;6:156–67.CrossRef Abdelhafiz AH, Rodriguez-Manas L, Morley JE, Sinclair AJ. Hypoglycemia in older people—a less well recognized risk factor for frailty. Aging Dis. 2015;6:156–67.CrossRef
40.
go back to reference Blaum CS, Ofstedal MB, Langa KM, Wray LA. Functional status and health outcomes in older Americans with diabetes mellitus. J Am Geriatr Soc. 2003;51:745–53.CrossRef Blaum CS, Ofstedal MB, Langa KM, Wray LA. Functional status and health outcomes in older Americans with diabetes mellitus. J Am Geriatr Soc. 2003;51:745–53.CrossRef
41.
go back to reference McGuire LC, Ford ES, Ajani UA. The impact of cognitive functioning on mortality and the development of functional disability in older adults with diabetes: the second longitudinal study on aging. BMC Geriatr. 2006;6:8.CrossRef McGuire LC, Ford ES, Ajani UA. The impact of cognitive functioning on mortality and the development of functional disability in older adults with diabetes: the second longitudinal study on aging. BMC Geriatr. 2006;6:8.CrossRef
42.
go back to reference Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011;34:1164–70.CrossRef Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011;34:1164–70.CrossRef
43.
go back to reference Lung TW, Petrie D, Herman WH, Palmer AJ, Svensson AM, Eliasson B, et al. Severe hypoglycemia and mortality after cardiovascular events for type 1 patients with diabetes in Sweden. Diabetes Care. 2014;37:2974–81.CrossRef Lung TW, Petrie D, Herman WH, Palmer AJ, Svensson AM, Eliasson B, et al. Severe hypoglycemia and mortality after cardiovascular events for type 1 patients with diabetes in Sweden. Diabetes Care. 2014;37:2974–81.CrossRef
44.
go back to reference Zaslavsky O, Walker RL, Crane PK, Gray SL, Larson EB. Glucose levels and risk of frailty. J Gerontol A Biol Sci Med Sci. 2016;71:1223–9.CrossRef Zaslavsky O, Walker RL, Crane PK, Gray SL, Larson EB. Glucose levels and risk of frailty. J Gerontol A Biol Sci Med Sci. 2016;71:1223–9.CrossRef
45.
go back to reference Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988;319:1701–7.CrossRef Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988;319:1701–7.CrossRef
46.
go back to reference Kojima G. Frailty as a predictor of future falls among community-dwelling older people: a systematic review and meta-analysis. J Am Med Dir Assoc. 2015;16:1027–33.CrossRef Kojima G. Frailty as a predictor of future falls among community-dwelling older people: a systematic review and meta-analysis. J Am Med Dir Assoc. 2015;16:1027–33.CrossRef
47.
go back to reference Yang Y, Hu X, Zhang Q, Zou R. Diabetes mellitus and risk of falls in older adults: a systematic review and meta-analysis. Age Ageing. 2016;45:761–7.CrossRef Yang Y, Hu X, Zhang Q, Zou R. Diabetes mellitus and risk of falls in older adults: a systematic review and meta-analysis. Age Ageing. 2016;45:761–7.CrossRef
48.
go back to reference Sinclair A, Dunning T, Rodriguez-Mañas L. Diabetes in older people: new insights and remaining challenges. Lancet Diabetes Endocrinol. 2015;3:275–85.CrossRef Sinclair A, Dunning T, Rodriguez-Mañas L. Diabetes in older people: new insights and remaining challenges. Lancet Diabetes Endocrinol. 2015;3:275–85.CrossRef
49.
go back to reference Rodriguez-Manas L, Fried LP. Frailty in the clinical scenario. Lancet. 2015;385:e7–9.CrossRef Rodriguez-Manas L, Fried LP. Frailty in the clinical scenario. Lancet. 2015;385:e7–9.CrossRef
Metadata
Title
Relationship between frailty and mortality, hospitalization, and cardiovascular diseases in diabetes: a systematic review and meta-analysis
Authors
Satoshi Ida
Ryutaro Kaneko
Kanako Imataka
Kazuya Murata
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2019
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-019-0885-2

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