Diabetes in Old Age

By Trisha Dunning

This new edition of the popular and market-leading Diabetes in Old Age features up-to-date and comprehensive information about the key aspects of managing older people with diabetes, predominantly type 2 diabetes.
With a strong evidence-based focus throughout, the entire range of issues surrounding diabetes and its many complications are covered, each with a clear focus on how they relate directly to the older patient. Varying approaches to optimizing diabetes care in the community, primary care and secondary care health care arenas are presented, and   the importance of comprehensive functional assessment is emphasized. Coverage of areas unique to an ageing population of older people with diabetes such as falls management, frailty and sarcopenia, and cognitive dysfunction form a key cornerstone of the book.  In every chapter, best practice points and key learning outcomes are provided, as well as published evidence bases for each major conclusion.

Diabetes in Old Age, 4th edition is essential reading for diabetologists and endocrinologists, diabetes specialist nurses, primary care physicians, general physicians and geriatricians, podiatrists and dieticians with an interest in diabetes, as well as all health professionals engaged in the delivery of diabetes care to older people.

• Language: English
• Publisher: Wiley
• Release date: Feb 13, 2017
• ISBN: 9781118954614

Book preview

SECTION A

Pathophysiology, screening and diagnosis

CHAPTER 1

Pathophysiology of diabetes in older people

Graydon S. Meneilly

Division of Geriatric Medicine, Department of Medicine, The University of British Columbia, Vancouver, Canada

KEY MESSAGES

Lifestyle factors play a major role in diabetes in the elderly.

Diabetes in the elderly is metabolically distinct.

Elderly patients with diabetes have an increase incidence of severe or fatal hypoglycemia.

1.1 Introduction

Numerous studies have been conducted to investigate the pathogenesis of type 2 diabetes [1]. Unfortunately, elderly patients were systematically excluded from these protocols. We have more recently started to study, in a systematic fashion, the pathophysiological alterations that occur in elderly patients with diabetes. These studies, the details of which will be reviewed in the following sections, suggest that there are many ways in which diabetes in the elderly is unique. Some of the factors that contribute to the high prevalence of diabetes in the elderly are shown schematically in Figure 1.1.

Overview of the factors that contribute to the high prevalence of diabetes in the elderly.

Figure 1.1 Factors that contribute to the high prevalence of diabetes in the elderly.

Reproduced with permission from Halter, J.B., Carbohydrate metabolism, in: E.J. Masoro (ed.), Handbook of Physiology, Volume on Aging. New York, Oxford University Press Inc., 1995, p. 119.

1.1.1 Genetic factors

There are several lines of evidence which suggest that there is a strong genetic component to diabetes in the elderly, although the specific genes responsible have yet to be defined [2]. If you have a family history of type 2 diabetes, you are much more likely to develop the disease as you age [3]. Diabetes is much more common in the elderly in certain ethnic groups [4], while the likelihood that an elderly identical twin will develop diabetes if their sibling is affected is over 80%. Even in elderly identical twins discordant for type 2 diabetes, the unaffected siblings clearly have evidence of abnormal glucose metabolism [5].

1.1.2 Age-related changes in carbohydrate metabolism

The progressive alterations in glucose metabolism that occur with age explain why genetically susceptible older individuals may not develop diabetes until late in life. Pathogenic mechanisms which contribute to the glucose intolerance of aging include alterations in glucose-induced insulin release and resistance to insulin-mediated glucose disposal [6]. Early investigations suggested that glucose-induced insulin release was normal in the elderly. However, more recent studies enrolling large numbers of carefully characterized healthy young and old subjects have demonstrated definable alterations in glucose-induced insulin release in the aged [6, 7]. Part of the reason for the decrease in insulin secretion is an impairment in islet mass and reduced β-cell proliferation [8]. In addition, the magnitude of the decrement in insulin secretion is more apparent in response to oral than to intravenous glucose [6]. This may be due, in part, to a decreased β-cell response to the incretin hormones (see below). As with many hormones, insulin is secreted in a pulsatile fashion. Normal aging is associated with subtle alterations in pulsatile insulin release, which further contribute to age-related changes in glucose metabolism [9]. Elevated levels of proinsulin, which suggest disordered insulin processing, predict the subsequent development of type 2 diabetes in elderly subjects [10]. Thus, it is clear that alterations in glucose-induced insulin release are an important component of the changes in carbohydrate metabolism with aging. However, the most important pathogenic mechanism underlying the glucose intolerance of aging is resistance to insulin-mediated glucose disposal [2, 6, 11]. Debate persists as to whether the insulin resistance of the elderly is intrinsic to the aging process itself, or is the result of lifestyle factors commonly associated with aging. The consensus of opinion is that the aging process itself is the most important cause of insulin resistance, although lifestyle changes are clearly an important contributing factor. The molecular and cellular changes contributing to insulin resistance are detailed below.

1.1.3 Lifestyle and environmental factors

Despite the strong genetic component, it is abundantly clear that various environmental and lifestyle factors can increase or decrease the likelihood that a genetically susceptible individual will develop the disease in old age. Many older people have coexisting illnesses and take multiple drugs (e.g., thiazide diuretics, antipsychotic drugs), which can allow a latent abnormality in glucose metabolism to develop into full-blown diabetes [12, 13]. Obesity, especially with a central distribution of body fat, and a reduction in physical activity as well as functional decline occur progressively with aging, and these factors are associated with abnormal carbohydrate metabolism and diabetes in the elderly [2, 13–21].

The above information suggests that lifestyle modifications may be of value in the prevention of type 2 diabetes in the elderly, even in patients with a strong family history of the disease. Indeed, the Diabetes Prevention Program found that a combined lifestyle intervention consisting of weight loss and increased physical activity was effective in reducing the incidence of diabetes in elderly patients with impaired glucose tolerance [22].

1.2 Diet and diabetes in the elderly

Diabetes is more likely to develop in older patients who have a diet that is high in saturated fats and simple sugars, and low in complex carbohydrates [14, 23–25]. Moderate alcohol consumption may protect against diabetes in elderly women [26]. It has been suggested that deficiencies of trace elements or vitamins may contribute to the development or progression of diabetes in younger subjects, and it is increasingly recognized that the same may be true in the elderly [13, 23]. Elderly patients with diabetes have exaggerated free radical production, and administration of the antioxidant vitamins C and E to these patients improves both insulin action and metabolic control [27, 28]. Some epidemiologic studies have shown an association between low levels of vitamin D and diabetes in the elderly [29–32] but others have not [33]. To date, there have been no trials to test the hypothesis that treatment with vitamin D in elderly patients predisposed to diabetes will prevent its development. There is a correlation between increased intake of vitamin K and a reduced incidence of diabetes in the elderly [34]. Many elderly patients with diabetes are deficient in magnesium and zinc, and supplements of zinc and magnesium can improve glucose metabolism [35–37]. Increased dietary iron may be associated with an increased risk of diabetes in aged individuals [38]. Although chromium deficiency has been shown to cause abnormalities in glucose metabolism in animals and younger patients, there is no evidence to date that chromium supplements will improve glucose tolerance in the elderly. There is also no evidence that selenium deficiency is associated with an increased risk of diabetes in the elderly [39]. Persistent organic pollutants and byproducts of plastics have been associated with diabetes in some studies [40, 41]. In summary, there is increasing evidence to suggest that dietary abnormalities or environmental factors may contribute to the pathogenesis of diabetes in the elderly, and that modifications of these parameters may be of therapeutic benefit.

1.3 Other factors

The presence of inflammation, as evidenced by elevated levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), cathepsin, and C-reactive protein (CRP), is associated with an increased risk of diabetes in the elderly [42–46]. Higher GGT levels, a marker of ongoing inflammation, are also associated with progression to diabetes in this age group [47]. Higher levels of adiponectin (an adipocytokine that increases insulin sensitivity) are associated with a reduced incidence of diabetes in the aged [48–52], whereas the opposite effect occurs with higher levels of fetuin-A, a protein that binds to the insulin receptor and inhibits insulin action. Sex steroid hormone levels also appear to be related to the development of diabetes in the elderly [53, 54]. In particular, higher testosterone levels in women and lower levels in men appear to be associated with an increased incidence of diabetes.

1.4 Metabolic alterations

The metabolic alterations which occur in middle-aged subjects with type 2 diabetes have been extensively characterized [1]. When compared to age- and weight-matched controls, both lean and obese middle-aged subjects have elevated fasting hepatic glucose production, a marked resistance to insulin-mediated glucose disposal, and a profound impairment in glucose-induced pancreatic insulin release.

Recently, metabolic factors have been characterized in lean and obese elderly patients with diabetes [55–58]. These studies have demonstrated some surprising differences in the metabolic profile between middle-aged and elderly subjects. In contrast to younger subjects, fasting hepatic glucose production is normal in both lean and obese elderly subjects (Figure 1.2). Similar to younger subjects, lean elderly patients have a profound impairment in pancreatic insulin secretion but, in contrast to the young, these patients have minimal resistance to insulin-mediated glucose disposal (Figures 1.3 and 1.4). In contradistinction to the young, obese elderly subjects have relatively preserved glucose-induced insulin secretion (see Figure 1.3), although pulsatile insulin secretion is clearly altered [8]. Similar to the young, however, these patients have a marked resistance to insulin-mediated glucose disposal (Figure 1.4). In summary, the principal defect in lean elderly subjects is impaired glucose-induced insulin release, while the principal defect in obese patients is resistance to insulin-mediated glucose disposal.

Plot depicting the fasting hepatic glucose production in relation to fasting glucose levels in healthy elderly controls and elderly patients with diabetes.

Figure 1.2 Fasting hepatic glucose production in relation to fasting glucose levels in healthy elderly controls and elderly patients with diabetes. Hepatic glucose production was measured by infusing radioactive glucose tracers.

Plot depicting Glucose-induced insulin release in healthy elderly controls and diabetic elderly patients.

Figure 1.3 Glucose-induced insulin release in healthy elderly controls and elderly patients with diabetes. Insulin values were measured at glucose levels approximately 5 mmol/l above fasting levels.

Histogram showing Insulin-mediated glucose disposal rates in healthy elderly controls and diabetic elderly patients.

Figure 1.4 Insulin-mediated glucose disposal rates in healthy elderly controls and elderly patients with diabetes. Glucose disposal rates were measured utilizing the euglycemic clamp technique. In this technique, insulin is infused to achieve levels occurring after a meal, and glucose is infused simultaneously to prevent hypoglycemia.

The ability of insulin to enhance blood flow is markedly reduced in obese, insulin-resistant older patients with diabetes (Figure 1.5) [57]. Insulin-mediated vasodilation is thought to account for about 30% of normal glucose disposal, presumably because it increases the delivery of insulin and glucose to muscle tissue. Indeed, it has been demonstrated that angiotensin-converting enzyme (ACE) inhibitors may improve insulin sensitivity in elderly patients with diabetes and hypertension [59]. This suggests that drugs which enhance muscle blood flow may prove to be valuable adjuncts in the future for the therapy of elderly patients with diabetes.

Plot depicting Insulin-mediated blood flow in obese middle-aged controls and obese elderly controls and diabetic patients.

Figure 1.5 Insulin-mediated blood flow in obese middle-aged controls and obese elderly controls and patients with diabetes. Blood flow was measured in the calf during euglycemic clamp studies utilizing venous occlusion plethysmography.

Autoimmune phenomena play a pivotal role in the β-cell failure that occurs in patients with type 1 diabetes [60]. It is increasingly recognized that a subset of middle-aged patients with type 2 diabetes have a form of diabetes that is characterized by β-cell failure, and these patients often have high titres of islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD), similar to younger patients with type 1 diabetes. These patients are said to have latent autoimmune diabetes in adults (LADA) [61–64]. It is tempting to speculate that autoimmune phenomena contribute to the profound impairment in glucose-induced insulin secretion seen in lean older patients with type 2 diabetes. However, the clinical significance of elevated antibodies in the elderly is less certain. Some studies have found that elderly patients with diabetes who are positive for GAD have impaired β-cell function relative to controls without these antibodies, but others have not [65, 66]. It has been suggested that screening for auto-antibodies should be performed in elderly patients with impaired glucose tolerance (IGT) and newly diagnosed diabetes in order to help predict which patients will develop islet cell failure. Although this is a compelling idea, we should only begin widespread screening when randomized studies have demonstrated that early intervention will protect the β cells and reduce the need for insulin therapy [63, 64]. Thus, it is unclear at present whether the measurement of autoimmune parameters can be used to predict future insulin requirements in the aged, or whether elderly patients with these abnormalities should be treated with therapies designed to modify autoimmune destruction of the pancreas.

Based on the above information, it is believed that the therapeutic approach to diabetes in the elderly should be different. In middle-aged patients, many endocrinologists recommend that patients be treated with drugs that both stimulate insulin secretion and improve insulin sensitivity, on the assumption that most patients have multiple metabolic problems. However, in lean elderly subjects the principal defect is an impairment in glucose-induced insulin secretion, and the main approach should be to administer secretogogues to stimulate insulin secretion, or to administer exogenous insulin. In obese elderly patients, the principal defect is insulin resistance; hence, patients should be treated initially with drugs that enhance insulin-mediated glucose disposal, such as metformin.

1.4.1 The incretin pathway

The enteroinsular axis refers to hormones released from the gut in response to nutrient ingestion that result in enhanced glucose-induced insulin release, known as the incretin effect. The most important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). When compared to younger controls, both basal and glucose-stimulated GIP and GLP-1 levels have been found to be unchanged or to be increased in healthy elderly subjects, and elderly patient with diabetes [67–70]. The level of dipeptidyl peptidase IV (DPIV), the enzyme that breaks down GIP and GLP-1, is progressively reduced with aging and diabetes. β-cell responses to GIP are reduced in normal elderly subjects and are absent in elderly patients with diabetes [71, 72]. In contrast, β-cell responses to GLP-1 are preserved in the elderly patient with diabetes [73]. These data suggest that GLP-1 and its analogues may prove to be useful therapeutic options in the elderly. This also suggests that agents which prevent the breakdown of GLP-1, such as DPIV inhibitors, may be less effective, although recent clinical trials do not support this hypothesis.

1.4.2 Glucose effectiveness or non-insulin-mediated glucose uptake

It has been recognized for many decades that insulin is an important hormone involved in the uptake of glucose into cells. It has also been demonstrated that glucose can stimulate its own uptake in the absence of insulin [74], an effect that is known as glucose effectiveness or non-insulin-mediated glucose uptake (NIMGU). Under fasting conditions, approximately 70% of glucose uptake occurs via glucose effectiveness, primarily in the central nervous system. After a meal, approximately 50% of glucose uptake in normal subjects occurs via NIMGU, with the bulk occurring in skeletal muscle. Because many middle-aged subjects with diabetes are insulin-resistant, it has been suggested that up to 80% of postprandial glucose uptake in these patients may occur via glucose effectiveness. At the present time it is uncertain whether defects in NIMGU contribute to elevated glucose levels in middle-aged patients with diabetes, as studies which have evaluated this parameter have provided inconsistent results.

In healthy elderly subjects glucose effectiveness is impaired during fasting, but is normal during hyperglycemia [75]. Elderly patients with diabetes have an even greater impairment in glucose effectiveness than healthy elderly subjects (Figure 1.6) [76]. Although the cause of this abnormality is uncertain, it may relate to a decreased ability of glucose to recruit glucose transporters to the cell surface.

Histogram showing Glucose effectiveness in elderly controls and diabetic patients.

Figure 1.6 Glucose effectiveness in elderly controls and patients with diabetes. During these studies, insulin secretion was suppressed by infusing the somatostatin analogue octreotide. Glucose was then infused to assess glucose disposal in the absence of insulin.

In the future, this metabolic abnormality may prove to be of great therapeutic relevance to the elderly. In younger patients, exercise, anabolic steroids and a reduction in free fatty acid levels have been shown to enhance glucose effectiveness [74]. Since we have shown that the incretin hormone GLP-1 may enhance NIMGU in elderly patients with diabetes [77], it is possible that future therapies for the elderly may be directed not only at increasing insulin secretion and reversing insulin resistance, but also at enhancing glucose effectiveness.

1.5 Molecular biology studies

At present there is limited information available regarding molecular biological abnormalities in elderly patients with diabetes. The glucokinase gene controls the glucose sensor for the β cell, and defects in this gene could lead to the impairment in glucose-induced insulin secretion in lean elderly patients with diabetes. To date, evidence for mutations in this gene in the elderly is conflicting [78, 79].

In skeletal muscle, insulin binds to its receptor, resulting in activation of the insulin receptor tyrosine kinase. Activation of this enzyme sets in motion a cascade of intracellular events that results in the translocation of glucose transporters to the cell surface. In theory, a defect in any of these pathways could lead to insulin resistance. To date, these intracellular processes have been incompletely studied in elderly patients with diabetes, but the preliminary information suggests that while insulin receptor numbers and affinity are normal, the insulin receptor kinase activity may be defective [80]. Recent data have suggested that mitochondrial dysfunction contributes to insulin resistance in middle-aged patients with diabetes, and potentially also to impairments in glucose-induced insulin release [81]. Age-associated reductions in mitochondrial number and function, possibly due to cumulative damage by reactive oxygen species (ROS), predispose the elderly to ectopic lipid accumulation and insulin resistance in muscle and liver [2, 8, 82, 83]. Preserving mitochondrial function by reducing mitochondrial oxidative damage may be a therapeutic target for preventing an age-associated reduction in mitochondrial function, insulin resistance, and type 2 diabetes. Although normal aging is characterized by progressive mitochondrial dysfunction, to date no studies have been performed to assess mitochondrial function in elderly patients with diabetes [83]. Clearly, further studies are required to elucidate the subcellular defects that cause abnormal glucose metabolism in the elderly patient with diabetes.

1.6 Glucose counter-regulation

Numerous studies have demonstrated that elderly patients with diabetes, when compared to younger patients, have an increased frequency of severe or fatal hypoglycemia [13, 84, 85]. Hypoglycemia is the second most common cause of iatrogenic admission to the hospital in the elderly [86]. Asymptomatic hypoglycemia is very common and can be prolonged [87], and it is frequently associated with cardiac abnormalities [88]. Several studies have evaluated glucose counter-regulation in elderly subjects in an attempt to determine the cause of the increased frequency of hypoglycemia, and a number of important observations have emerged. Many elderly patients with diabetes have not been educated about the warning symptoms of hypoglycemia and as a result do not know how to interpret these symptoms when they occur [89].

The most important hormone in the defense against hypoglycemia in normal subjects is glucagon. If glucagon responses are deficient, epinephrine becomes important, and growth hormone and cortisol come into play if hypoglycemia is prolonged. The responses of both glucagon and growth hormone to hypoglycemia are impaired in healthy elderly subjects, and to an even greater extent in older patients with diabetes (Figure 1.7) [90], although the responses do not differ from middle-aged patients with diabetes [91]. Yet, even when they are educated about the symptoms of hypoglycemia, the elderly have a reduced awareness of the autonomic and neuroglycopenic warning symptoms at glucose levels that would elicit a marked response in younger subjects (bremer, meneilly). Finally, elderly patients have an impaired psychomotor performance during hypoglycemia [90, 91], which would prevent them from taking steps to return the blood glucose value to normal, even if they were aware that it was low. Thus, the increased frequency of hypoglycemia in the elderly is due to a constellation of abnormalities, including reduced knowledge and awareness of the warning symptoms, decreased counter-regulatory hormone secretion, and altered psychomotor performance.

Plot for Glucagon and growth hormone (GH) responses to hypoglycemia in healthy young, healthy old, and elderly patients with diabetes.

Figure 1.7 Glucagon and growth hormone (GH) responses to hypoglycemia in healthy young, healthy old, and elderly patients with diabetes. Controlled hypoglycemia was induced using the glucose clamp technique. Glucose values at which hormone levels were measured are shown on the top x-axis.

Levels of pancreatic polypeptide (PP) are elevated during hypoglycemia, and this response is mediated by the vagus nerve. The role of PP in normal glucose counter-regulation is uncertain, but in younger patients with diabetes a reduced PP response to hypoglycemia is an early marker of autonomic insufficiency. Although elderly patients with diabetes often have evidence of autonomic dysfunction, their PP responses to hypoglycemia are normal [92]. Thus, PP responses to hypoglycemia cannot be used to predict autonomic function in elderly patients.

Based on the above information, there are a number of interventions that can be proposed to prevent hypoglycemic events in the elderly. First, it would seem prudent to educate elderly patients about the warning symptoms of hypoglycemia so that they can appreciate them when they occur. Second, consideration should be given to the use of oral agents or insulin preparations that are associated with a lower frequency of hypoglycemic events in the elderly.

1.7 Conclusions

In summary, diabetes in older people is caused by a combination of genetic and environmental factors superimposed on the normal age-related changes in carbohydrate metabolism. The metabolic alterations that occur in elderly patients with diabetes appear to be distinct from those that occur in younger patients. As we gain a greater appreciation of the pathophysiological abnormalities that occur in the elderly, we hope to be able to develop a more focused approach to therapy in this age group. It is only in this way that we will be able to better cope with the epidemic of diabetes in the elderly that will befall us in the coming decades.

Acknowledgments

The studies described in this chapter were supported by grants from the Canadian Institutes of Health Research and the Canadian Diabetes Association. I gratefully acknowledge the support of the Allan McGavin Geriatric Endowment at the University of British Columbia, and the Jack Bell Geriatric Endowment Fund at Vancouver Hospital and Health Science Centre.

I am especially indebted to my longstanding collaborators in this work, particularly Dr Dariush Elahi and Dr Daniel Tessier. I thank Rosemarie Torressani, Gale Tedder, Eugene Mar, Gail Chin, and Christine Lockhart for technical assistance in conducting these studies.

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CHAPTER 2

Type 1 diabetes in older age

Medha Munshi¹ and Alan J. Sinclair²

¹Director of Joslin Geriatric Diabetes Programs, Beth Israel Deaconess Medical Center, Harvard University, USA

²Director of Diabetes Frail Ltd and Honorary Professor of Metabolic Medicine, University of Aston, Birmingham, UK

KEY MESSAGES

Many older individuals with type 1 diabetes are highly disciplined and proactive in regards to their health and have lived for many years with a complex disease.

Type 1 diabetes is increasingly being diagnosed in individuals aged 60 years and over.

The primary management goal in older patients with type 1 disease remains the same as in younger patients, preventing acute and chronic complications associated with this disease, but there is the additional need to maintain functional status.

The cautions used in treating aging adults with type 2 diabetes, in particular the focus on overall health goals and prevention of treatment-related complications (especially hypoglycemia), also remain important in those with type 1 disease.

Co-morbidities commonly found in aging patients with type 2 diabetes, such as cognitive dysfunction, depression, physical disabilities, and polypharmacy, are also likely to coexist in older adults with type 1 disease.

Insulin regimes can be advised according to the capability of patients to self-manage, the need for the individualized approach, and the need to attain sensible and realistic glucose targets.

2.1 Introduction

Traditionally, type 1 diabetes mellitus was thought to be a disease of children and younger adults. Over the past few decades understanding regarding the pathophysiology of diabetes has improved, leading to improvement in the management of the disease, as well as longer life expectancy for people with type 1 diabetes. As a result of the success in managing younger patients with type 1 diabetes, and the recognition that type 1 diabetes occurs in consistent numbers in all adult decades, healthcare providers have started managing a higher number of older adults with type 1 disease and these represent a small but unique population. These individuals are highly disciplined and proactive in regards to their health and have lived for many years with a complex disease. The exact prevalence of type 1 diabetes mellitus in this age group is not known, but is probably increasing as the population is aging. Based on the prevalence of type 1 diabetes in the younger population, and variable life expectancy in different parts of the world, the prevalence of type 1 diabetes in older adults is also likely to vary significantly among countries [1]. The differences in characteristics of older patients with type 1 and type 2 diabetes are noted in Table 2.1.

Table 2.1 Characteristics of older patients with type 1 or type 2 diabetes.

2.2 Goals in the management of type 1 diabetes in older adults

Although there is a paucity of data guiding the management of older persons with type 1 diabetes, small studies and expert analysis in the recent past have provided better understanding of how to manage the aging population with type 2 diabetes (http://www.idf.org/guidelines/managing-older-people-type-2-diabetes) [2–4].

As patients with type 1 diabetes mellitus age, they face additional challenges based on the presence of coexisting medical conditions, which may interfere with the self-care they have performed for many decades. Changes in their social and functional environment may also interfere with their self-care abilities. Overall, as in older patients with type 2 diabetes, the primary management goal in older patients with type 1 disease remains the same as in younger patients, preventing acute and chronic complications associated with this disease, but there is the additional need to maintain functional status. Similarly, the cautions used in treating aging adults with type 2, in particular the focus on overall health goals and prevention of treatment-related complications (especially hypoglycemia), also remain important in those with type 1 disease.

One major difference seen between older adults with type 2 diabetes and those with type 1 diabetes is the discipline they have maintained over many decades to successfully manage their diabetes and keep glycemic control in a tight range. This behavior is typically deeply rooted. However, as patients with type 1 diabetes age, they also develop diabetes-related and diabetes-unrelated co-morbid conditions, functional decline, and the need for caregiver support. Although many older adults with type 1 diabetes continue to successfully manage their diabetes, the complex interaction with additional conditions may interfere with their ability to continue aiming for strict glycemic control and execute routine tasks previously performed for decades, such as rigorous glucose monitoring, complex insulin dose management, pump and continuous glucose monitoring operation, and maintaining dietary compliance. It is important to observe these patients closely for warning signs of decompensation such as coping difficulties or multiple errors in medications/insulin regimen, which may manifest as a change in diabetes control with frequent hypoglycemia or hyperglycemia. Careful discussion regarding risks and benefits of tight control needs to be undertaken at that point to avoid catastrophic consequences of hypoglycemia, such as traumatic falls. We have indicated in Table 2.2 a plan for insulin therapy according to the health and functional status of older people with type 1 diabetes.

Table 2.2 Therapy approach and glycemic targets for type 1 diabetes in older people.

2.3 Complications and co-morbidities

Several observational studies have followed patients with type 1 diabetes as they age and have reported the rate of complications. A cross-sectional observational study of over 350 patients with type 1 diabetes mellitus for a duration of >50 years in the USA reported that glycemic control (HbA1c) was not associated with the risk of complications in this population [5]. This long-surviving population also had very few microvascular and macrovascular complications, suggesting that they may have protective factors against diabetes complications. More studies are needed to understand the factors that might be responsible for this protection. Another study analyzed data from 350 diabetes centers treating over 64,000 patients with type 1 diabetes in Germany [6]. This analysis showed that older patients with type 1 diabetes (>60 years of age) had a higher risk of both macrovascular and microvascular complications compared to their younger counterparts. This older cohort also had lower HbA1c levels (7.6% vs 8.3%) and almost double the risk of hypoglycemia compared with the younger cohort. Such observational data underscores the importance of individualizing glycemic goals as well as treatment strategies in older patients with type 1 diabetes.

Co-morbidities commonly found in aging patients with type 2 diabetes, such as cognitive dysfunction, depression, physical disabilities, and polypharmacy, are also likely to coexist in older adults with type 1 disease. Recently, much attention has focused on the high risk of cognitive dysfunction, as it presents a major barrier in performing self-care [7]. Several studies have shown a link between type 2 diabetes and dementia, and the association is thought to be bidirectional [8, 9]. However, there are fewer studies evaluating type 1 diabetes and neurocognitive disorders in older adults. One study evaluated the volume and severity of white matter hyper-intensities in middle-aged (mean age 50 years) patients with childhood-onset type 1 diabetes and compared them with age-matched controls without diabetes [10]. The results showed that patients with type 1 disease had an earlier presentation of clinically relevant white matter hyper-intensities associated with slower information processing compared to controls. A small study assessed the levels of circulating biomarkers in cerebrospinal fluid (CSF) of middle-aged patients with type 1 diabetes and compared them to age-matched controls [11]. The researchers found higher levels of biomarkers of Alzheimer’s disease, including phosphorylated tau, beta-amyloid 42, and a soluble form of low-density lipoprotein receptor-related protein (sLRP1) in CSF of patients with type 1 disease compared to the controls.

Other population-based studies have evaluated the associations between cognitive dysfunction and diabetes. A recent study evaluated 12-year follow-up data on people >60 years of age belonging to a large US health system. They found 230 patients with type 1 diabetes out of over 490,000 patients on the database. The results showed that older adults with type 1 diabetes were 83% more likely to develop dementia compared with those without the disease [12]. Another prospective study also evaluated cognitive function in 200 patients over the age of 60 years with type 1 diabetes [13]. The authors found that 36–44% of the study patients had cognitive dysfunction as measured by the Montreal Cognitive Assessment (MOCA) tool (available at http://www.mocatest.org) and the trails-making test, respectively. A meta-analysis performed on 33 studies evaluated cognitive dysfunction in patients with type 1 diabetes [14]. The results of the study showed impairment in certain domains of cognitive function, such as mental speed and mental flexibilities. In this study, learning and memory were spared. This type of executive dysfunction is important for self-care behaviors and may lead to errors when complex coping skills are needed. However, this area still needs more investigation, as seen by other small studies reporting variable results. A small longitudinal study that followed 36 patients with type 1 diabetes (mean age 60 ± 6 years; median follow-up 4.1 years) did not show any greater cognitive decline in individuals with type 1 diabetes compared to age-matched controls [15]. However, in this study the subgroup with one or more cardiovascular or hypoglycemic events was found to be more likely to develop cognitive decline. Thus, the data linking cognitive dysfunction to type 1 diabetes are not as robust as those linking to type 2 diabetes. Nonetheless, aging independently also increases the risk of cognitive dysfunction and thus screening for subtle cognitive/executive dysfunction is important in all older patients with diabetes due to its impact on self-care abilities.

The relationship between diabetes and depression has been studied extensively. Similar to cognitive dysfunction, the association between diabetes and depression is thought to be bidirectional. The prevalence of depression in type 1 diabetes is difficult to assess due to the different methods used by different epidemiological studies with sometimes conflicting results. A meta-analysis evaluating the cross-sectional prevalence of clinical depression in patients with type 1 diabetes found inadequate evidence to conclude that the prevalence of depression is different in adult patients with type 1 diabetes (ages 21–43 years) compared to the general population [16]. This study did not include any older adults. Other smaller studies have shown an association between depression in adults with type 1 diabetes and metabolic syndrome [17] and subclinical carotid atherosclerosis in men [18]. Depression in older adults with type 2 diabetes has shown associations with poor glycemic control, decreased adherence to treatment strategies, increased functional disability, and mortality [19–21]. However, studies evaluating these associations in older patients with type 1 diabetes are lacking. Nonetheless, it is important to be aware of the relationship between diabetes, depression, and self-care abilities.

Polypharmacy is a challenging aspect of caring for older adults with multiple chronic diseases. Although complex regimens are generally avoided in older patients with type 2 diabetes, patients with type 1 diabetes frequently need complex insulin regimens to maintain good glycemic control. In general, older patients with both type 1 and type 2 diabetes need more medications to control cardiovascular risk factors associated with diabetes and manage other non-diabetes-related co-morbidities. Polypharmacy is found to increase the risk of non-adherence, drug–drug interactions, side effects, and errors leading to catastrophic consequences [22, 23]. In addition, multiple consultants and lack of coordination of care amongst them can lead to further errors. The general principle of medication reconciliation at each visit is an important part of managing older patients with type 1 diabetes.

Aging and its impact on overall physical function, health status, vision, hearing, chronic pain, and falls leads to high risks of loss of independence and the need for more caregiver support [24, 25]. As many of the barriers to optimal diabetes management develop gradually with subtle presentations, it is important to periodically assess older type 1 diabetes mellitus individuals for physical, social, and emotional/cognitive dysfunctions.

2.4 Hypoglycemia

Risk of hypoglycemia is the primary consideration when establishing glycemic goals in all older adults. In this population, the benefits of tight glycemic control are limited, while the immediate consequences of hypoglycemia can be devastating and may include cardiac and cerebrovascular events, progression of dementia, injurious falls, emergency department visits, and hospitalizations [26–28]. The decline in overall functioning may even lead to institutionalization with unacceptable decline in quality of life. Although most of the findings are in older adults with type 2 diabetes and have not been replicated in patients with type 1 diabetes specifically, the risk of hypoglycemia increases with longer duration of the disease, treatment with insulin, and high complexity of the treatment regimen, all of which are more common in type 1 patients [29, 30]. In addition, many co-morbidities associated with poor outcomes are likely to be age dependent and may affect older patients with both type 1 and type 2 disease. One difference frequently seen between older adults with type 2 and type 1 diabetes is that many older patients with type 2 diabetes are afraid of the adverse effects of hypoglycemia (e.g., falling and confusion) and over-treat lows, leading to widely fluctuating blood glucose readings. Paradoxically, many older adults with type1 diabetes are less concerned about hypoglycemic risks as they are accustomed to them, which leads to frequent episodes that are not managed well. In these older patients, appropriate and repeated education is needed as the hypoglycemic consequences may be more deleterious than those of hyperglycemia.

Most experts recommend a liberal goal for HbA1c to avoid hypoglycemia in vulnerable older patients with type 1 and type 2 diabetes. It is important to remember that higher HbA1c values in insulin-treated patients frequently suggest wide fluctuations of glucose levels and do not reflect lower risk of hypoglycemia [31]. Simplified strategies that match older patients’ coping abilities are the best way to prevent hypoglycemia [32].

2.5 Multidisciplinary team approach

It has been well established that optimal diabetes management in all patients requires input from a team that consists of an endocrinologist, a diabetes-educator, a nutritionist, an exercise physiologist, and a psychologist. Older patients with type 1 diabetes may benefit from additional services beyond the traditional teams, such as clinical pharmacists, physical and occupational therapists, and rehabilitation services that take into account clinical, functional, and psychosocial diversity [33]. Caregivers, both formal (such as visiting nurses) and informal (family members or friends), also are an important part of the team caring for older adults with type 1 diabetes who are not able to perform self-care. Diabetes education for patients and caregivers, as well as treatment strategies, need to be flexible since they frequently change due to new obstacles or a decline in the individual’s support structure. Resources such as visiting nurses and physical therapists might be available for housebound patients or post hospitalization for a short time, but delirium and deconditioning may last longer in frail type 1 diabetes mellitus patients. These patients may need a simplified insulin regimen and more caregiver support for a variable time. Personal and community resources are important, especially for patients with type 1 diabetes who are living alone, and these resources may dictate how the patient can be managed.

2.6 Long-term care

The prevalence of type 1 diabetes in long-term care facilities is not currently known, but with longer life expectancy we are bound to see an increasing number of older patients with type 1 disease in long-term care settings. Most published guidelines describing the principles of diabetes management in nursing homes are focused on the management of type 2 diabetes [34, 35]. It is important to educate long-term care facility staff members on diabetes management as they become the primary caregiver for the patients admitted there and perform most of the self-care for patients who are not able to perform this themselves anymore. The education should include the unique challenges facing patients with type 1 diabetes, as compared to commonly seen type 2 diabetes, an overview of the different insulins, interaction between insulin and carbohydrate content of meals, and hypoglycemia recognition and treatment.

2.7 Conclusion

Older adults with type 1 diabetes are a unique population, and are often proactive in their approach to their health care. These patients have mastered their diabetes management and typically feel strongly about controlling their hyperglycemia tightly. Typically, the role of the provider is to continue to support the patients in their effort to manage their diabetes. On the other hand, they do develop age-related impairments and co-morbidities that may interfere with complex management. With increasing functional disability and difficulty performing self-care, there is a high risk of errors in insulin dosing, meal planning or insulin/meal timing. These errors can result in wide glucose fluctuations and lead to great frustration on the part of the patients and caregivers. It is common to see frequent hypoglycemic episodes in older patients with type 1 diabetes who are not concerned about the repercussions, as they have had these episodes since childhood. Subtle executive dysfunction makes it difficult for patients to change behaviors that have been rooted for many decades. Repeated education for patients and caregivers, and patience on the part of medical providers, is needed for successful aging and the best possible quality of life, in addition to good diabetes care.

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