|Year : 2015 | Volume
| Issue : 3 | Page : 115-120
Study of frailty index in elderly men with type 2 diabetes mellitus
Marwa AM Saad1, Samar M Abd El-Fattah2, Mohamed S Gad1, Akram M Deghady3
1 Department of Internal Medicine, Geriatric Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Internal Medicine, Moustafa Kamel Military Hospital, Alexandria, Egypt
3 Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
|Date of Web Publication||9-Mar-2016|
Marwa AM Saad
MD, Department of Internal Medicine, Geriatric Unit, Faculty of Medicine, Alexandria University, Alexandria
Source of Support: None, Conflict of Interest: None
Frailty is a common and growing multidimensional health and social care challenge across the world. Diabetes mellitus (DM) is one of the most important causes of morbidity and mortality in Egypt. Frailty and diabetes are inter-related. In addition, diabetes causes early-onset frailty. In this study we aimed to determine the frailty index in elderly men with type 2 DM and compare it with that in pre-elderly diabetic patients and age-matched healthy controls.
Materials and methods
Seventy male participants were included in the present study and were divided into three groups. Group I comprised 20 healthy men aged 65-75 years who were considered the control group; group II comprised 25 patients aged 50-64 years with type 2 DM; and group III comprised 25 patients aged 65-75 years with type 2 DM. Patients on insulin therapy and those with hypogonadism or hypothyroidism were excluded from the study. Frailty index was determined for all participants using Fried's five phenotypic parameters. Patients were considered frail if they fulfilled more than or equal to three parameters, prefrail if they fulfilled one to two parameters, and nonfrail if they fulfilled none of the parameters. Data were collected, analyzed, and compared between groups I and III and between groups II and III. Further, frailty index was correlated with the duration of DM and the degree of glycemic control.
Seventy patients were divided into three groups. The mean age in group I was 68.50 ± 1.90 years, that in group II was 58.24 ± 4.34 years, and that in group III was 68.60 ± 2.43 years. Regarding the frailty index, in group I 17 patients (85%) were nonfrail, three (15%) were prefrail, and none were frail; in group II, four patients (16%) were prefrail, 21 (84%) were frail, and none were nonfrail; and in group III, three patients (12%) were prefrail, 22 (88%) were frail, and none were nonfrail. A statistically significant difference was noted between groups I and III, whereas no significant difference was noted between groups II and III. A significant positive correlation was found between the frailty index score and duration of diabetes and degree of glycemic control in groups II and III.
Diabetes and frailty are causally related. Diabetes is associated with frailty at earlier age. The duration of diabetes and degree of glycemic control correlate with the severity of frailty in both elderly and pre-elderly diabetic patients.
Keywords: Diabetes mellitus, elderly, frailty
|How to cite this article:|
Saad MA, Abd El-Fattah SM, Gad MS, Deghady AM. Study of frailty index in elderly men with type 2 diabetes mellitus. Egypt J Obes Diabetes Endocrinol 2015;1:115-20
|How to cite this URL:|
Saad MA, Abd El-Fattah SM, Gad MS, Deghady AM. Study of frailty index in elderly men with type 2 diabetes mellitus. Egypt J Obes Diabetes Endocrinol [serial online] 2015 [cited 2020 Jul 8];1:115-20. Available from: http://www.ejode.eg.net/text.asp?2015/1/3/115/178291
| Introduction|| |
Aging is an important part of human life, affecting all societies and cultures . Roughly 100 000 people worldwide die each day of age-related causes . Aging of the overall population is a significant driver of the diabetes epidemic . Diabetes has a prevalence of 10-30% in people above 65 years of age. It is a premature aging syndrome, a cause of unsuccessful aging, and a disabling syndrome . It is associated with disability, morbidity, mortality, and institutionalization . Diabetic men and women diagnosed at age 60 have an estimated reduction in life expectancy of 7.3-9.5 years, and a good quality of life of 11.1-13.8 years . Diabetes is the 11th most important cause of premature mortality in Egypt and is responsible for 2.4% of all years of life lost. Similarly, diabetes is the sixth most important cause of disability in Egypt . Diabetic patients are at greater risk for several common geriatric syndromes such as polypharmacy, depression, cognitive impairment, urinary incontinence, infections, pressure ulcers, and falls and hip fractures in the elderly . The disease is also associated with a decrease in leisure activities, a decline in quality of life, and an increase in the requirement of healthcare . Current standards of diabetes care do not specify a different approach to frailty in a setting of diabetes . It has been proposed that diabetes in aging patients may be associated with frailty at an earlier stage than in nondiabetic counterparts ,.
Frailty is described as a state of increased vulnerability to stressors that results from decreased physiological reserve in multiple systems that causes limited capacity to maintain homeostasis . The prevalence of frailty in the elderly has been described to be between 7 and 30% in different population studies . It has been reported that frailty is a state associated with major adverse health and social events, including mortality, disability, institutionalization, and dependency . Although frailty is more prevalent in older people and in those with multiple medical conditions, it can exist independently of age, disability, or disease and may be an independent physiologic process involving multiple systems . Fried et al.  proposed that the factors involved in aging include neuromuscular abnormalities, deregulation of the neuroendocrine system, dysfunction of the immunological system, and a cycle of frailty. The main components would be chronic malnutrition, sarcopenia, decline in physical activities, and totally consumed energy. The result is a loss of functional capacity and limited energy reserve at a cellular level and in day-to-day activities ,. Hormones are key regulators of human muscle metabolism, and age-related hormonal changes are important biological contributors to skeletal muscle decline, with an accelerated loss of muscle mass and frailty . Total testosterone declines at the rate of ∼1% per year in men as they age, and this is associated with a decline in muscle mass and strength, bone mineral density, and cognition. Also, a number of symptoms of frailty, such as fatigue, are associated with low testosterone levels . In addition, it has been described that low testosterone levels are associated with insulin resistance and that testosterone treatment may reduce insulin resistance ,. Other hormones involved in frailty are dehydroepiandrosterone , insulin-like growth factor-1 , and 25-hydroxyvitamin D . All have been shown to decline with aging. Thyroid hormone derangement as a part of physiological changes of aging plays a role in the pathogenesis of frailty. Hypothyroidism and hyperthyroidism are associated with a decline in muscle strength and cognitive dysfunction and thus can produce frailty .
There are different diagnostic criteria for frailty, with no consensus in the literature as to the most adequate markers for its identification. However, Fried et al.  defined a clinical phenotype of frailty identified by the presence of three or more of the following components :
- Weight loss: unintentional loss of 4.5 kg or more in the past year;
- Weakness: assessed by hand-grip strength and adjusted for sex and BMI;
- Exhaustion: self-reported poor endurance and energy;
- Slowness: based on the time needed to complete a series of functionally important tasks (adjusted for sex and height); and
- Low physical activity level: lowest quintile of kilocalories of physical activity during the last week, measured with the Minnesota Leisure Activity Scale.
Diabetic patients tend to have worse function than nondiabetic individuals, which is associated with an accelerated decline in muscle function. The metabolic changes in diabetes result in changes in the connective tissue and structure of a muscle ,. Skeletal muscle weakness, which is a key component of frailty and muscle dysfunction, can be influenced by both fatty infiltration of muscle tissue, insulin resistance, increased levels of cytokines, and increased levels of adiponectin ,. Motor endplates play an important role in maintaining muscle mass and coordinating muscle contraction. Diabetes is associated with peripheral neuropathy and a decrease in motor endplates, leading to loss of muscle function ,. The conditions necessary for frailty develop faster in diabetic patients than in other aging individuals; therefore, appropriate treatment for diabetes mellitus (DM) and frailty precursors can slow down the aging process ,.
It has been hypothesized that diabetes and frailty are inter-related  and that diabetes can cause premature frailty. We aimed in the present study to determine the frailty index in elderly men with type 2 DM and compare it with that in pre-elderly diabetic patients and age-matched healthy controls.
| Materials and methods|| |
The present study included 70 men who attended the Geriatric Outpatient Clinic, Moustafa Kamel Military Hospital, during the period from November 2014 to July 2015. Participants were divided into three groups. Group I included 20 healthy men aged 65-75 years as a control group; group II included 25 patients with type 2 DM aged 50-64 years; and group III included 25 patients with type 2 DM aged 65-75 years. Patients on insulin therapy, patients with chronic systemic diseases such as hepatic or renal diseases, and those with hypothyroidism or hypogonadism were excluded from the study. The purpose and benefit of the study were explained to all participants, and informed written consent was obtained. The proposal was approved by the ethical committee of the Faculty of Medicine, Alexandria University.
A detailed medical history was taken from each participant of groups II and III with special emphasis on onset, duration, and treatment of DM. Blood samples were collected from all participants and sent for basic laboratory investigations, including assessment of serum thyroid stimulating hormone and free testosterone hormone levels. Frailty index was determined for all participants; patients were classified as frail if they fulfilled three or more of the following parameters, prefrail if they fulfilled one or two parameters, and nonfrail if they fulfilled none of the following parameters ,.
- Weight loss: self-reported unintentional weight loss of 4.5 kg or more in the previous year.
- Weakness (i.e. low hand-grip strength): determined by grip strength of the dominant hand (mean of three measurements) using a Jamar hand-held dynamometer. The patient holds the dynamometer in the hand to be tested, with the arm at right angles and the elbow by the side of the body. The base should rest on the first metacarpal, and the handle should rest on the middle of four fingers. When ready the patient squeezes the dynamometer with maximum isometric effort, which is maintained for about 5 s. No other body movement is allowed. The patient should be strongly encouraged to give maximum effort. The cutoff points adjusted for BMI were ≤32 kg for BMI>28, ≤30 kg for BMI 24.1-28, and ≤29 kg for BMI≤24.
- Poor endurance (i.e. self-reported exhaustion): evaluated using two statements from the center for epidemiological studies depression Scale: (a) 'I felt that everything I did was an effort' and (b) 'I could not get going'. The patients tested positive for poor endurance if they fulfilled at least one condition for 3 days or more during the last week.
- Slowness: evaluated using the timed get up and go test that requires the patient to stand up from a chair, walk a distance of 6 m, turn around, return, and sit down again. It thus serves as an assessment of dynamic balance. Balance function is observed and scored (normal value 17 s).
- Low physical activity level: participants who reported not performing daily leisure activities such as walking or gardening and/or some sport activity per week were categorized as physically inactive.
Data were collected and coded and then entered into an IBM compatible computer using the StatView software version 5.1 for windows (SAS, Inc.). Qualitative variables were expressed as number and percentage. Quantitative variables were expressed as minimum and maximum as well as mean and SD. Exact tests such as Fisher's exact and the Monte Carlo were also applied. Non-normally distributed quantitative data were analyzed using nonparametric tests such as the Mann-Whitney test and the Kruskal-Wallis test. Pearson's coefficient was used to analyze the correlation between the different parameters. Statistical significance was considered at P less than or equal to 0.05.
Group III was compared with their age-matched controls in group I, and group II was compared with group III. Frailty index was correlated with the duration of diabetes in groups II and III, and also with the glycemic control state.
| Results|| |
A total of 70 men were included in the present study. Participants were divided into three groups according to their age. The age range in group I was 65-72 years, with a mean of 68.50 ± 1.90 years; the age range in group II was 50-64 years, with a mean of 58.24 ± 4.34 years; and the age range in group III was 65-73 years, with a mean of 68.60 ± 2.43 years [Table 1].
In group II, 11 patients (44%) had been diabetic since 5-10 years, with a mean of 8.09 ± 1.22 years; eight patients (32%) had been diabetic since 11-15 years, with a mean of 13.63 ± 1.30 years; and six patients (24%) had been diabetic since more than 15 years, with a mean of 22.67 ± 1.75 years. In group III, five patients (20%) had been diabetic since 5-10 years, with a mean of 9.00 ± 1.23 years; 11 patients (44%) had been diabetic since 11-15 years, with a mean of 13.00 ± 1.27 years; and nine patients (36%) had been diabetic since more than 15 years, with a mean of 23.67 ± 4.27 years. No statistically significant difference regarding the duration of diabetes was noted between the two studied groups.
Frailty index score showed the following results: in group I, 17 patients (85%) were nonfrail, three (15%) were prefrail, and none were frail; in group II, four patients (16%) were prefrail, 21 (84%) were frail, and none were nonfrail; and in group III, three patients (12%) were prefrail, 22 (88%) were frail, and none were nonfrail. There was significant difference between groups I and III (t = 13.40, P<0.001), but there was no significant difference between groups II and III (t = 1.213, P = 0.231) [Table 2].
|Table 2: Comparison between the studied groups regarding frailty score index|
Click here to view
A significant positive correlation was found between the frailty index score and duration of diabetes and degree of glycemic control in groups II and III [Table 3].
|Table 3: Correlations of frailty index scores in groups II and III with the duration of diabetes and the degree of diabetic control|
Click here to view
| Discussion|| |
Aging is characterized by diverse deleterious changes in cells and tissues that are responsible for the increased risk for morbidity and mortality . Frailty is a common clinical syndrome in older adults that carries an increased risk for poor health outcomes including falls, incident disability, hospitalization, and mortality . The factors implicated in the pathogenesis of frailty include endocrine changes and inflammatory cytokines ,,,. DM is a common condition in older individuals; diabetic patients tend to have an accelerated aging process that places them at greater risk for developing frailty at an earlier age . In the present study, we investigated the correlation between frailty parameters and DM in elderly and pre-elderly men. Seventy men were included in this study and were divided into three groups. There was a statistically significant difference in the frailty index between group III (mean age 68.60 ± 2.43 years) and group I (mean age 68.50 ± 1.90 years), indicating the impact of DM on elderly diabetic patients. Also, a positive significant correlation was found between the duration of diabetes, degree of glycemic control, and frailty index in such patients. In group II (mean age 58.24 ± 4.34 years), 21 patients (83%) were frail, whereas only four patients (16%) were prefrail, and none were nonfrail, indicating the deleterious effect of diabetes in this age group causing early-onset frailty.
In accordance with our results is the study by Park et al.  that included 3075 diabetic adults aged 70-79 years. Muscle strength was lower in men with diabetes. Also, longer duration of diabetes and poorer glycemic control were associated with poorer muscle strength.
Cetinus et al.  studied hand-grip strength in 76 middle-aged, diabetic patients with a mean age of 50.11 years. Hand-grip strength was found to be lower in patients with type 2 DM than in age-matched controls. Shambhuvani et al.  assessed the effect of long-standing DM type 2 on hand-grip strength in 25 patients with diabetes since more than 6 years, who were of a mean age of 60.96 years. Grip strength was significantly reduced in diabetic individuals as compared with nondiabetic individuals.
Several studies have suggested that type 2 DM is associated with the development of frailty in the elderly ,. Studies also suggest that persons aged 55 years or older should be screened for frailty ,.
García-Esquinas et al.  assessed the role of diabetes as a risk factor for frailty. The study included 1750 individuals (346 diabetic individuals) aged 60 years or older. The study participants were followed up to assess incident frailty. The study showed that over a mean follow-up of 3.5 years, 115 cases of incident frailty were ascertained. After adjustment for age, sex, and education, participants with diabetes showed an increased risk for frailty. They concluded that DM was associated with higher risk for frailty; this association was partly explained by unhealthy behaviors and obesity and, to a greater extent, by poor glucose control and altered serum lipid profile among diabetic individuals. Conversely, nutritional therapy to counter diabetes reduced the risk for frailty.
Also, Bouillon et al.  examined whether established diabetes risk factors were associated with future frailty in a prospective cohort study that included 2707 participants (72% men) aged 45-69 years. In that study, after a mean follow-up of 10.5 years 2.8% of the sample was classified as frail and 37.5% as prefrail. Increased age, being female, smoking, poor glycemic control, low physical activity, and not having a daily consumption of fruits and vegetables were each associated with frailty or prefrailty.
Low-grade chronic inflammation and impaired immune response have been noted as important factors that increase patient susceptibility to multiple chronic disease states including diabetes. In addition, increased inflammation is associated with lower muscle mass and strength and increased functional decline . Thus, DM as a chronic disease associated with a chronic state of low-grade inflammation is associated with frailty.
| Conclusion|| |
Frailty is a common and growing multidimensional health and social care challenge across the world. Diabetes and frailty are causally related and operate through each of the key components of the frailty phenotype or through associated medical comorbidities. The presence of frailty in a setting of diabetes increases the level of disability and leads to poorer clinical outcomes. Diabetes is associated with frailty at earlier age. The duration of diabetes and degree of glycemic control correlate with the severity of frailty.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Avendano M, Glymour MM, Banks J, Mackenbach JP. Health disadvantage in US adults aged 50 to 74 years: a comparison of the health of rich and poor Americans with that of Europeans. Am J Public Health 2009; 99:540-548.
Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet 2009; 374:1196-1208.
Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2011. Atlanta, GA: Department of Health and Human Services, Centers for Disease Control and Prevention; 2011.
Sinclair AJ, Meneilly GS. Type 2 diabetes mellitus in senior citizens. In: John Pathy MS, Sinclair AJ, Morley JE, eds Principles and practice of geriatric medicine
. 4th ed. Chichester, UK: Wiley; 2006:1431-1445.
Rockwood K, Awalt E, MacKnight C, McDowell I. Incidence and outcomes of diabetes mellitus in elderly people: report from the Canadian Study of Health and Aging. CMAJ 2000; 162:769-772.
Morley JE. Diabetes and aging: epidemiologic overview. Clin Geriatr Med 2008; 24:395-405.
National Center of Health and Population (NICHP). The burden of disease and injury in Egypt (mortality and morbidity); 2004
Sinclair AJ. Diabetes in the elderly: a perspective from the United Kingdom. Clin Geriatr Med 1999; 15:225-237.
American Diabetes Association. Standards of medical care in diabetes; 2011: 34
Morley JE, Kim MJ, Haren MT. Frailty and hormones. Rev Endocr Metab Disord 2005; 6:101-108.
Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 2004; 59:255-263.
Rockwood K, Howlett SE, MacKnight C, Beattie BL, Bergman H, Hébert R, et al.
Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and anging. J Gerontol A Biol Sci Med Sci 2004; 59:1310-1317.
Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL, et al
. Women′s Health Initiative Frailty: emergence and consequences in women aged 65 and older in the Women′s Health Initiative Observational Study. J Am Geriatr Soc 2005; 53:1321-1330.
Ottenbacher KJ, Ostir GV, Peek MK, Snih SA, Raji MA, Markides KS. Frailty in older Mexican Americans. J Am Geriatr Soc 2005; 53:1524-1531.
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al
. Cardiovascular Health Study Collaborative Research Group Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56:M146-M156.
Chin A Paw MJ, de Groot LC, van Gend SV, Schoterman MH, Schouten EG, Schroll M, van Staveren WA. Inactivity and weight loss: effective criteria to identify frailty. J Nutr Health Aging 2003; 7:55-60.
Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 2002; 50:889-896.
Cappola AR, Xue QL, Fried LP. Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women′s Health and Aging studies. J Gerontol A Biol Sci Med Sci 2009; 64:243-248.
Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 2003; 58:618-625.
Spark RF. Testosterone, diabetes mellitus, and the metabolic syndrome. Curr Urol Rep 2007; 8:467-471.
Morley JE. Is the hormonal fountain of youth drying up? J Gerontol A Biol Sci Med Sci 2004; 59:458-460.
Valenti G, Denti L, Maggio M, Ceda G, Volpato S, Bandinelli S, et al.
Effect of DHEAS on skeletal muscle over the life span: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 2004; 59:466-472.
Harman SM, Blackman MR. Use of growth hormone for prevention or treatment of effects of aging. J Gerontol A Biol Sci Med Sci 2004; 59:652-658.
Wilhelm-Leen ER, Hall YN, Deboer IH, Chertow GM. Vitamin D deficiency and frailty in older Americans. J Intern Med 2010; 268:171-180.
Yeap BB, Alfonso H, Chubb SA, Walsh JP, Hankey GJ, Almeida OP, Flicker L. Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study. Clin Endocrinol (Oxf). 2012; 76:741-748.
Casellini, CM, Vinik AI. Clinical manifestations and current treatment options for diabetic neuropathies. Endocr Pract 2007; 13:550-566.
Sakkas GK, Kent-Braun JA, Doyle JW, Shubert T, Gordon P, Johansen KL. Effect of diabetes mellitus on muscle size and strength in patients receiving dialysis therapy. Am J Kidney Dis 2006; 47:862-869.
Francis GJ, Martinez JA, Liu WQ, Zochodne DW, Hanson LR, Frey WH, Toth C. Motor end plate innervation loss in diabetes and the role of insulin. J Neuropathol Exp Neurol 2011; 70:323-339.
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-S22.
Amer MS, Khater MS, Adly NN, El Maraghy MO Insulin resistance and cognitive functions in a sample of pre-frail, frail and non-frail elderly. Adv Aging Res 2014; 3:177-186.
Hayflick L. How and why we age. Exp Gerontol 1998; 33:639-653.
Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, et al.
Phenotype of frailty: characterization in the women′s health and aging studies. J Gerontol A Biol Sci Med Sci. 2006; 61:262-266.
Abdelhafiz AH, Sinclair AJ. Low HbA1c and increased mortality risk-is frailty a confounding factor? Aging Dis 2015; 6:262-270.
Park SW, Goodpaster BH, Strotmeyer ES, de Rekeneire N, Harris TB, Schwartz AV, et al
. Decreased muscle strength and quality in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes 2006; 55:1813-1818.
Cetinus E, Buyukbese MA, Uzel M, Ekerbicer H, Karaoguz A. Hand grip strength in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2005; 70:278-286.
Shambhuvani M, Diwan S, Vyas N. Effect of longstanding diabetes mellitus II on handgrip strength: an observational study. IAIM 2015; 2:135-139.
Khallaf M, Fayed E, Al-Rashidi M. Effect of longstanding diabetes mellitus type II on hand grip strength and pinch power of females in the city of Hail-KSA. IOSR-JNHS 2014; 3:41-44.
Seo Y, Hahm J, Kim T, Choi W. Factors affecting fatigue in patients with type II diabetes mellitus in Korea. Asian Nurs Res (Korean Soc Nurs Sci) 2015; 9:60-64.
Saum KU, Dieffenbach AK, Müller 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; 29:171-179.
Jung HW, Kim SW, Ahn S, Lim JY, Han JW, Kim TH, et al
. Prevalence and outcomes of frailty in Korean elderly population: comparisons of a multidimensional frailty index with two phenotype models. PLoS One 2014; 9:e87958.
García-Esquinas E, Graciani A, Guallar-Castillón P, López-García E, Rodríguez-Mañas L, Rodríguez-Artalejo F. Diabetes and risk of frailty and its potential mechanisms: a prospective cohort study of older adults. J Am Med Dir Assoc 2015; 16:748-754.
Bouillon K, Kivimäki M, Hamer M, Shipley MJ, Akbaraly TN, Tabak A, et al.
Diabetes risk factors, diabetes risk algorithms, and the prediction of future frailty: the Whitehall II prospective cohort study. J Am Med Dir Assoc 2013; 14:851.e1-6.
Li H, Manwani B, Leng SX. Frailty, inflammation, and immunity. Aging Dis 2011; 2:466-473.
[Table 1], [Table 2], [Table 3]