Dr Atsushi Araki MD PhD, Department of Endocrinology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Tokyo 173-0015, Japan. Email: firstname.lastname@example.org
Diabetes mellitus is associated with an increased prevalence and incidence of geriatric syndrome: functional disabilities, depression, fall, urinary incontinence, malnutrition and cognitive impairment. Geriatric syndrome not only leads to frailty, loss of independence and low quality of life, but also becomes a major obstacle in the treatment and care of diabetic people. The risk factors or contributing factors of geriatric symptoms are micro- and macrovascular complications, age-rated comorbid disease and aging per se. Comprehensive geriatric assessment of geriatric syndrome, including basic activities of daily living, instrumental activities of daily living, gait and balance, visual acuity, the Mini-Mental State Examination, depression scores, history and risk of fall, urination and nutrition, should be performed as part of the care of elderly diabetic patients, in particular old-old patients. Because geriatric syndromes are multifactorial and share risk factors, diabetic people with any geriatric symptoms should be treated with a common concentric strategy, such as supervised exercise therapy including muscle-strengthening training, psychological support, social support for adherence, and good glycemic control with avoidance of hypoglycemia.
Diabetes mellitus is more common in the elderly population. At least one-sixth of the elderly population has diabetes mellitus in Japan and other countries.1,2 The treatment of diabetes mellitus in the elderly population, in particular the old-old people, is often difficult because of impairment of their physical, psychological and cognitive functions, and the lack or shortage of family or social support. Elderly diabetic patients may have increased risk for functional dependency and frailty. Therefore, a comprehensive geriatric assessment may be a necessity in the treatment of elderly patients.3
Another important approach to diabetes in the elderly is the assessment, prevention and treatment of geriatric syndrome. The so-called “geriatric syndrome” refers to multifactorial health conditions that occur when the accumulated effects on multiple systems render an old person vulnerable to situational changes.4 Geriatric syndrome is related to the impairment of multiple systems due to aging as well as age-related disease. Diabetes mellitus is considered to lead to accelerated aging because of both the accumulation of advanced glycation end products, a marker of aging, in the tissues and the high incidence of atherosclerotic disease compared with non-diabetic populations. Also, because the development of diabetic micro- and macrovascular complications is dependent on the duration of diabetes, symptoms of the complications may be concentrated in the elderly. The diabetes population has a high prevalence of geriatric syndrome such as functional disabilities, depression, fall, urinary incontinence, pain and dementia, which occur due to the aging and diabetic complications. The geriatric symptoms lead to frailty, loss of independence and low quality of life. Importantly, these geriatric symptoms are major obstacles in the treatment and care of diabetic people.
In this article, we review geriatric symptoms in diabetes mellitus and discuss an approach to the assessment, prevention, and treatment of geriatric syndromes in diabetic people.
Diabetes and functional disability
One of the most serious geriatric symptoms is functional disability. Cross-sectional studies in the USA showed that diabetes was associated with a twofold increased risk of being unable to perform daily physical tasks.5,6 Gregg et al. showed that, among 6588 community-dwelling individuals aged 60 years or more, 32% of women and 15% of men reported an inability to walk one-quarter of a mile, do housework or climb stairs, compared with 14% of women and 8% of men without diabetes, respectively.5 The Women's Health and Aging Study reported that women with diabetes had a 1.6-fold greater risk of basic activities of daily living (bADL) disability (bathing, transferring from bed to chair, using the toilet, dressing and eating) and a 2.3-fold greater risk of severe walking limitation.6 We assessed the disability of 1135 elderly diabetic outpatients using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC; 13 items), which included instrumental activities of daily living (IADL) (tasks of using public transportation, shopping for daily necessities, preparing meals, paying bill and handling one's own banking), intellectual activity (ability to complete the pension form; to read newspapers, books or magazines; and to be interested in news stories or programs dealing with health) and social role.7 The prevalence of disability on at least one item of the TMIG-IC was approximately 45%. When we divided the subjects into three age groups, the oldest group (aged ≥80 years) reported a higher prevalence of disabilities for IADL, such as using public transportation, shopping, preparing meals and paying bills, compared with the youngest group (aged 65–69 years) (Fig. 1). A prospective study of women aged 65 years or more in the Study of Osteoporosis Fractures also demonstrated that diabetes was associated with a 2- to 2.5-fold increased incidence of functional disability for doing housework or walking two or three blocks.8 Coronary heart disease (CHD), obesity (women), stroke (men), peripheral artery disease (PVD), neuropathy, arthritis and depression were important contributors to diabetes-related functional disabilities in US studies.5,8 In contrast, in a Japanese study, a low sense of well-being, insulin treatment, cognitive impairment and visual impairment were associated with functional disabilities after adjustment for age, sex, body mass index (BMI), duration of diabetes, HbA1c, microangiopathy and macroangiopathy.7 In addition to diabetic complications, aging per se contributed to diabetes-related disability, which may lead to difficulty in performing self-care activities such as exercise and diet therapy.
Diabetes and depression or low sense of well-being
The prevalence and incidence of depressive symptoms are greater in diabetic than in non-diabetic people. Approximately 30% of people with diabetes have depressive symptoms, while 5–10% have major depression.9 The Health, Aging, and Body Composition Study, a cohort study of subjects aged 70–79 years, showed that diabetic people had an increased incidence of depressed mood compared with those without diabetes (23.5% vs 19.0%; hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.07–1.61).10 A community-based study in Spanish elderly subjects demonstrated that diabetes was associated with an increased risk of prevalent depression (odds ratio [OR], 1.47; CI, 1.16–1.83) and incident depression (HR, 1.40; CI, 1.03–1.90).11 Because the presence of comorbid diseases increased the risk of incident depression, diabetes may play a role in the development of depression in the elderly.
The presence of high levels of depressive symptoms based on the Center for Epidemiologic Studies Depression Scale (CES-D) score of 16 or more was associated with diabetic complications, any activities of daily living (ADL) or IADL disabilities, urinary incontinence, visual impairment, poor perceived health status and increased number of hospitalizations.9
The impact of depression on disability is much greater in diabetic patients than in non-diabetic subjects. With no diabetes and no major depression as references, the adjusted OR of functional disability was 7.2 for people with diabetes and comorbid major depression, which was high compared with the OR of 2.4 for people with diabetes alone and 3.0 for those who had major depression alone.12
Reduced well-being or quality of life should be considered as part of the geriatric syndrome. When well-being, which included the concept of positive feeling of happiness, life satisfaction and acceptance of aging as well as negative affects, was assessed using the Philadelphia Geriatric Center (PGC) morale scale in elderly people with diabetes, approximately 19% of them had a low sense of well-being (PGC morale score, ≤7). People with a low sense of well-being had 2- to 3-fold increased odds for disability on the TMIG-IC, except for shopping and use of transportation.7 Multivariate analysis revealed that sex (female), macroangiopathy, high frequency of hypoglycemia, negative social support and reduced positive social support were independently associated with a low sense of well-being.13
Interestingly, a low sense of well-being was an independent predictor of stroke after adjustment for conventional risk factors in our 3-year follow-up study.14 Similarly, depression also predicted stroke and cardiovascular disease independent of the other risk factors.15,16 The association between depression or a low sense of well-being and atherosclerotic disease may be explained by the activation of platelets,17 an activated sympathetic nervous system and the increased expression of inflammatory markers. The use of specific antidepressant agents, such as selective serotonin reuptake inhibitors (SSRI), inhibited the activation of platelets in patients with depression17 and prevented the development of myocardial infarction.18
Depression predicted increased mortality, greater incidences of macro- and microvascular complications, and disability in ADL in older people with type 2 diabetes mellitus.19 The interaction between depression and diabetes in old people (aged ≥65 years) was found to have a synergistic effect on adverse outcomes. Therefore, aggravation of psychological function in diabetic people may lead to adverse outcomes (micro- and macrovascular complications, disabilities and increased mortality) through multifactorial mechanisms.
Diabetes and falling
Falls may lead to fractures, aggravation of glycemic control and reduction of quality of life in diabetic people. Even non-injurious falls can result in a post-fall syndrome characterized by anxiety and reduced physical and social activities.
A growing amount of evidence suggests that diabetes mellitus is one of the major predictors of the risk of falling.20,21 The Study of Osteoporotic Fractures, which involved 9247 women aged 67 years or more, showed that 18% of older women fell more than once a year. They showed that both non-insulin-treated and insulin-treated people with diabetes had an increased risk of falling compared with non-diabetic people (OR, 1.68; CI, 1.37–2.07; and OR, 2.78; CI, 1.82–4.25, respectively).20 The Women's Health and Aging Study demonstrated that diabetes was associated with an increased risk of falling among disabled old women.21 These studies show that poor lower extremity function, poor balance, a history of CHD, a history of arthritis, musculoskeletal pain, depression, poor vision, medication and peripheral neuropathy, overweight and insulin therapy are important predictors of falling among diabetic women.20,21
The increased risk of falling may be partially explained by the impairment of gait balance and gait in diabetic people.22–24 A study reported that diabetic patients had poorer balance during standing in diminished light, and increased sway during standing.22 Diabetes was associated with an increased risk of gait disturbance due to Parkinson's disease-like symptoms in a 9-year follow up of people aged 75 years and over.23 Diabetic individuals with peripheral neuropathy had impaired peripheral sensation and reaction time, and had impaired ability to stabilize their body when walking on irregular surfaces.24 They also had reduced walking speed and step length, and less rhythmic acceleration patterns at the head and pelvis compared with controls.
Diabetes and urinary incontinence
Diabetes is associated with increased risk of both stress incontinence and urge incontinence.25–27 Furthermore, overflow incontinence can occur as a complication of autonomic neuropathy in diabetic people. Diabetic women have a threefold increased prevalence of urge incontinence and twice the prevalence of stress incontinence.25 The association between diabetes and urinary incontinence was confirmed with a prospective study of 81 854 women for any incontinence (HR, 1.21; CI, 1.02–1.43) and for severe incontinence (HR, 1.40; CI, 1.15–1.71).26 A cross-sectional study of postmenopausal women aged 55–75 years showed that 52% of diabetic women with diabetes had some form of incontinence in the past month and 15% had severe incontinence, and that diabetic women were more likely to have severe incontinence or mixed incontinence.27 The study also showed that diabetes duration, neuropathy, retinopathy and a history of urinary tract infection were independently associated with severe incontinence in multivariate analysis, and that the association decreased after adjustment for BMI. In contrast, a lifestyle intervention that included weight reduction decreased the frequency of stress incontinence in the Diabetes Prevention Program Trial.28
Diabetes mellitus and malnutrition
Elderly people with diabetes may be at risk of malnutrition as compared with non-diabetic people. A case-control study showed that community-dwelling diabetic people had significantly lower scores of Mini-Nutritional Assessment (MNA) than non-diabetic subjects.29 Anorexia due to morbidity (infectious disease, end-stage renal failure or malignancy), drug adverse effects and excessive dietary restriction may be responsible for the malnutrition in older diabetic people. Because subclinical deficiencies in vitamin B groups (B1, B2, B12, B6 and folate) in the elderly are associated with cognitive impairment or decline,30 sufficient intake of vitamin and micronutrients may be necessary in elderly patients with diabetes.
Even diabetic patients who are obese or have metabolic syndrome can be modified and overshadowed by malnutrition, which is associated with low BMI and low levels of leptin and insulin.31 Sarcopenic obesity, which is defined as excess fat with loss of lean body mass, may be a major problem in the diabetic patients. Sarcopenic obesity preceded the onset of IADL disability in a community-dwelling elderly population.32 The increased production of inflammatory adipokines may alter insulin sensitivity and muscle mass and strength in sarcopenic obesity in diabetic patients.
Malnutrition in the elderly leads to increased mortality, disability and life-threatening complications.33,34 Because we found that people who had serum albumin levels of less than 3.5 mg/dL showed increased mortality in a 6-year follow-up study of 422 elderly diabetic patients (HR, 4.2; CI, 1.3–13.9) (A Araki et al. unpublished data) malnutrition should be included as important geriatric symptoms.
Diabetes and cognitive impairment
Diabetes mellitus is associated with moderate deficits in specific cognitive function domains, such as complex psychomotor skills, speed of information processing, and memory and learning.35–37 Epidemiological studies have shown that the diabetic population has a 1.6- to 3.0-fold increased risk for Alzheimer's-type dementia and vascular dementia.38,39 Hyperglycemia,35–37 advanced glycation end products,40 recurrent severe hypoglycemia,41 symptomatic and asymptomatic cerebrovascular disease,37 polyneuropathy,42 insulin treatment,38 hyperinsulinemia or insulin resistance,43 depression,44 and low serum albumin44 were associated with cognitive impairment in diabetes mellitus. Cognitive impairment was predicted by brain structural changes, subcortical atrophy and subcortical white matter hyperintensity, cortical atrophy in the parietal lobe and thalamus, as well as cortical atrophy.45 Probably decreased cerebral blood flow and hyperglycemia-induced metabolic derangement are involved in the pathogenesis of the diabetic complications in the central nervous system, which refers to diabetic encephalopathy. Cognitive function may be one of the important factors related to poor adherence to diabetic self-care activities, increased frequency of hospitalization, and increased need for assistance in personal care in older adults with diabetes.46
Glycemic control in the short term has some favorable effects on cognitive function in diabetic people. In particular, moderate impairment of learning, memory, and complex psychomotor skill was partially improved by glycemic control with oral drugs or insulin therapy for 3 weeks.40,47
Although insulin-treated diabetic patients had an increased risk of cognitive impairment or dementia,38,39 the association may be explained by increased cerebral complications rather than effects of insulin in insulin-treated patients. In contrast, a defect in insulin signaling or insulin resistance in the brain has been proposed as one cause of Alzheimer's disease.48 Treatment with intranasal insulin, which selectively acted on the central nervous system, improved the impairment of memory saving, attention and functional status in patients in the early stage of Alzheimer's disease.49 Therefore, insulin may have some beneficial effects on cognition.
Glucose control and geriatric syndrome
Remarkable hyperglycemia may directly cause several forms of geriatric syndrome: functional disability due to general malaise, urinary incontinence due to polyuria, malnutrition due to increased protein catabolism and cognitive impairment. Poor glucose control in the long term also potentially affects forms of geriatric syndrome such as cognitive function and susceptibility to infection.
There is limited data as to what level should be an appropriate treatment goal of HbA1c for elderly people with diabetes. Gao et al. demonstrated that, in a longitudinal study of 1139 people aged 65 years and over in England and Wales, diabetic individuals who had HbA1c levels of 7.0% or had a significantly higher risk of all-cause and cardiovascular mortality, and dementia compared with the three tertiles of the subjects (HbA1c: 3.7%–5.2%, 5.3%–5.7%, and 5.8%–6.9%), suggesting a HbA1c goal of 7.0% or less.50
Interestingly, glucose control may affect the incidence of falling in people with diabetes. The Health, Aging and Body Composition Study involving a cohort of well-functioning older adults showed that, among those using insulin, HbA1c of 6% or less increased the risk of falls, although no association between HbA1c level and oral hypoglycemic medications was observed.51 Nelson et al. pointed out that the risk of falling in community-dwelling diabetic people aged 75 years or more markedly increased when HbA1c was 7% or less, regardless of frailty status.52 Although the frequency of hypoglycemia was not assessed in these studies, atypical hypoglycemic symptoms (e.g. unsteadiness, poor coordination, double vision and dizziness) have been considered to cause falling in elderly diabetic individuals.53 Severe hypoglycemia may lead to transient depression as well as cognitive impairment.54 Therefore, we consider that, for well-functioning diabetic people free of geriatric syndrome, a HbA1c level between 6.5% and 7.0% would be an ideal goal in order to prevent severe hypoglycemia, diabetic complications, dementia and death.
In contrast, for elderly people with multiple symptoms of geriatric syndrome (i.e. geriatric syndromes) and multiple morbidities, the glucose control should be individualized. The “Guidelines for improving the care of older persons with diabetes mellitus” proposed that treatment goals for blood glucose in older people with diabetes may be individually determined based on age, life expectancy, patient preference and the presence of geriatric syndrome: depression, pain, falls, incontinence, polypharmacy and cognitive impairment.55,56 Huang et al. calculated expected benefits of intensive glucose control (HbA1c level of 7.0%) versus moderate glucose control (HbA1c level of 7.9%) in a diabetic population 60–80 years of age as a quality-adjusted life expectancy from a decision analysis.57 They showed that the expected quality of life benefit of intensive control was 106 days at 60–64 years of age and decreased to 52 days at 75–79 years of age with no comorbid illness or functional impairment. They also demonstrated that for people at 60–64 years of age who had had diabetes for 10–15 years the expected benefits decreased from 116 days for those who were at baseline good health (life expectancy, 13.5 years) to 36 days for those with 4 additional mortality index points, which was calculated from comorbid illnesses and functional impairment (life expectancy, 8.0 years) and to 8 days for those with 8 additional mortality index points (life expectancy, 3.9 years). Thus, in some diabetic patients with multiple morbidity and multiple functional impairments (such as dementia, disability and the other three serious diseases), the goal of a HbA1c level of less than 8.0% might be acceptable.
Geriatric syndromes and their risk factors
The prevalence, odds ratio and risk factors of the typical geriatric syndromes are shown in Table 1. Old diabetic people consistently have an increased risk of geriatric syndrome: functional disability, depression, falling, urinary incontinence, malnutrition and cognitive impairment. As shown in Figure 2, the aging per se, diabetic micro- and macrovascular complications (in particular autonomic neuropathy), hyperglycemia and hypoglycemia are risk factors for the geriatric syndromes. Multiple morbidity and lack of social support also may lead to the aggravation of geriatric syndrome in diabetic people. Some forms of geriatric syndrome such as depression and cognitive impairment adversely affect the risk factors: hyperglycemia and micro- and macrovascular complications to form a vicious cycle, leading to the increased mortality. The geriatric syndromes are multifactorial and interrelated, and share risk factors. For example, depression or reduced well-being is thought to be one of risk factors for disability, fall, cognitive impairment and malnutrition.
Table 1. Prevalence, odds ratio, and risk factors for geriatric syndromes in diabetic people
Prevalence or incidence
Odds ratio (95% CI)
ADL, activities of daily living; BMI, body mass index; CHD, coronary heart disease; CI, confidence interval; DM, diabetes mellitus; MMSE, Mini-Mental State Examination; OR, odds ratio; PVD, peripheral artery disease.
Based on the results discussed above, it is necessary to assess geriatric syndromes when treating diabetic patients, in particular old-old patients. Comprehensive geriatric assessment of geriatric syndromes including bADL, IADL, gait and balance, visual acuity, Mini-Mental State Examination, geriatric depression scores, history and risk of falling and urination status should be performed, as shown in Table 2. The assessment of family or social support, living accommodation and surroundings is also important. The measurement of both supine and standing blood pressures, residual urine volume, and electrocardiogram coefficient of variation of R-R variations may be helpful in the geriatric assessment of diabetic people because autonomic neuropathy may be involved in some geriatric syndromes.
Table 2. Assessment of typical geriatric syndromes in diabetes mellitus
Tools and risk assessment
Basic activities of daily living (ADL), instrumental ADL
Depression or low quality of life
15-Item Geriatric Depression Scale (GDS-15, GDS-5), PGC morale scale
Frequency of fall, gait, balance, blood pressures (supine and standing)
Frequency and severity of incontinence, postvoid residual urine volume, nocturia
Mini-Mental State Examination (MMSE)
Subjective global assessment (SGA), Mini-Nutritional Assessment (MNA), objective data assessment (e.g. serum albumin, BMI, lymphocyte number)
Intervention in geriatric syndrome
The treatment of diabetic patients with geriatric syndrome should focus on a strategy for preventing the aggravation of geriatric syndrome.
The importance of exercise therapy, compared with diet therapy, may be greater in elderly than in younger patients. Muscle-strengthening training, as well as aerobic exercise, led by supervisors or exercise professionals is necessary in order to prevent the worsening of disability and to maintain good glycemic control.
Supervised resistance training for 16 weeks improved the muscle strength of the lower extremities, ADL and glycemic control in elderly patients with diabetes.58 Supervised exercise may be one of the common strategies for the prevention of forms of geriatric syndromes (disability, depression, fall and cognitive impairment).
A fall prevention program should be implemented for diabetic individuals with geriatric syndrome. Multidisciplinary, multifactorial, health or environmental risk factor screening intervention programs; programs of muscle strengthening and balance training, home hazard assessment and withdrawal of psychotropic medication; and Tai Chi group exercise intervention may be effective in preventing falls in diabetic individuals.59
Psychological intervention,60 such as counseling, group therapy, cognitive behavioral therapy, social support and exercise training,61 may be necessary for the treatment of old diabetic patients with depressive symptoms or low sense of well-being. Anti-depressive medication, including SSRI drugs, may be indicated in patients with diabetes and comorbid depression for the prevention of diabetic complications and increased mortality.
Diabetic women with urinary incontinence should be given exercise treatment, including pelvic floor muscle training,62,63 weight reduction,28 training mobility and toileting skills64 for stress incontinence. Biofeedback therapy and behavioral training may be also effective for urge incontinence.65
Intensive care and social support are necessary for elderly people with diabetes and cognitive impairment. The management of cardiovascular risk factors, community-based supervised exercise, day-service activities and support for adherence to medication or insulin injection regimens may be helpful in the management of patients with both diabetes and cognitive impairment.
The avoidance of hypoglycemia and the ability to cope well with hypoglycemia may be also important for the prevention of falling and maintenance of well-being in elderly diabetic people. Prevention of hypoglycemia requires monitoring of HbA1c and self-monitoring of blood glucose, meticulous adjustment of sulfonylureas and insulin dosage, and educating patients, their families and care staff in coping skills for hypoglycemia and sick days.
Common strategy for geriatric syndrome
Because geriatric syndromes are multifactorial and share risk factors, a concentric approach, focusing on pathways associated with risk factor synergism, may be effective in the care of those who have geriatric syndromes.4 Therefore, diabetic people with any geriatric symptoms could be treated with a multidisciplinary common concentric strategy: supervised exercise therapy including muscle-strengthening training, psychological support, social support for adherence to anti-diabetic medications or insulin, and good glycemic control with avoidance of hypoglycemia. Further studies are necessary including randomized trials of the efficacy of multidisciplinary common strategies based on geriatric syndrome in diabetic individuals.