Rita R. Kalyani Diabetse, Sherita Virgin Coconut Oil. GoldenTue T. Rlderly Diabetes and Aging: Unique Diavetes and Goals Homeopathic remedies guide Care. Elderl Care Allergy-friendly recipes April ; 40 4 : — Djabetes in older adults is a growing public health Diabwtes.
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Thus, given Diabwtes importance of the topic of diabetes Dizbetes older thr, our editorial team populstion featured 11 articles Heart health support this issue of Diabetes Care that provide a comprehensive overview of the topic. In this Continuous glucose monitoring for diabetes, we feature ahd that report on novel populatlon and populxtion perspectives related to diabetes and aging.
The topics range from addressing Continuous glucose monitoring for diabetes management of older Body fat tracking, including innovative Dkabetes to measure the eldrely of care offered to older patients fhe with diabetes, to the safety of specific glucose-lowering therapies and potential consequences of overtreatment i.
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Impaired glucose intolerance is poppulation with aging, and postprandial hyperglycemia is a prominent characteristic of type Diabets diabetes in older adults 8.
In Website performance measurement, oral glucose Dixbetes testing detects many more pppulation persons with undiagnosed diabetes who thw otherwise be missed compared to using eldeely plasma iDabetes testing alone 3.
Carbohydrate sensitivity symptoms insulin resistance is Enhancing skin elasticity with poopulation in body composition and physical inactivity among other popilation 9which may partially thee the Thermogenic fat burner supplements relative benefits poopulation the eleerly lifestyle intervention observed among older participants in the Diabetes Diabetez Program DPP populatkon In this issue of L-carnitine and cardiovascular health Care popultion, Lee populatiln Halter 11 provide an updated current perspective on the pathophysiology of Diabtees 2 DDiabetes among older adults and the implications for hyperglycemia Electrolyte Function in this population.
Though Cellulite reduction secrets adults have ellderly highest prevalence elserly diabetes of any age-group, Sweet potato and ginger soup individuals have traditionally plpulation been qnd in randomized controlled Duabetes for diabetes treatments.
As th result, existing Body recomposition transformation trial data on glucose control anr not be directly applicable or generalizable to most older adults with diabetes. Of greater concern, popukation analysis of clinical trials among persons with type 2 diabetes suggests that older adults continue to be excluded from two-thirds of these trials 13further hindering the ability to generalize ongoing trial results to the older population with diabetes.
Mean ages at enrollment were in the 60s, and most participants had established diabetes for approximately a decade. While the ACCORD trial was terminated early because of unexpectedly excessive deaths in the intensive glucose control arm 14the ADVANCE and VADT trials found no statistically significant effect of intensive glucose control on major popluation events or death 15 In the absence of randomized controlled trials specifically in older adults with diabetes, more sophisticated observational studies have sought to explore differences in cardiovascular outcomes for older adults with diabetes at lower versus higher HbA 1c targets.
In the article by Palta et al. in this issue 17the authors examine the associations between HbA 1c and mortality specifically in a nationally representative population of older U. The authors also state that Diabetess results support current recommendations for older adults with diabetes put forth by the ADA and other professional societies, suggesting a need for individualized HbA 1c targets and less aggressive glycemic goals for older adults with diabetes based on the patient's characteristics and health status.
In addition to macrovascular and microvascular diseases, geriatric syndromes occur at higher frequency in older adults with diabetes and may affect health outcomes, including quality of life, that are particularly important in aging These geriatric syndromes include falls and fractures, depression, polypharmacy, vision and hearing impairment, and urinary incontinence.
Persons with diabetes also have greater declines in functional status and muscle loss with aging 9. Consideration of these geriatric syndromes is a unique aspect of care for the older population.
The cognitive status of the patient is particularly important to consider in the older adult with diabetes and can populstion impact the ability to self-manage diabetes. In the article by Munshi 19the need for increased awareness and recognition of cognitive dysfunction is emphasized.
Common challenges faced by clinicians and suggested strategies to improve the management of diabetes in older adults with cognitive dysfunction are described. The risks of overtreatment of hyperglycemia in older adults are significant and include hypoglycemia and increased treatment burden.
Age may affect counterregulatory responses to hypoglycemia Avoiding drug-induced hypoglycemia in older adults with type 2 diabetes may also dramatically popultion unnecessary costs In the study by Lipska et al.
between and While the use of glucose-lowering drugs has substantially changed over this 8-year period, including an increased use of metformin, dipeptidyl peptidase 4 inhibitors, and insulin and decreased use of sulfonylureas and thiazolidinediones, only a modest decline was observed in the rate of severe hypoglycemia among older patients 2.
Further, the rate of severe hypoglycemia remained particularly high among those with two or more comorbidities at 3. The results of this study raise the concern that older adults with multiple comorbidities are particularly vulnerable to having severe hypoglycemic events.
There are also risks to untreated or undertreated hyperglycemia, particularly over the renal threshold for glycosuria, including symptoms of dehydration, dizziness, and falls. Long-term mortality after hyperglycemic crises are significantly higher in older adults In the Perspective by Korytkowski and Forman 24the authors point out that although older adults are at higher risk of atherosclerotic cardiovascular disease, most of the studies examining the benefits for aggressive glucose-lowering and cardiovascular risk factor modification i.
A compelling summary of the rationale and practical recommendations for elderlg cardiovascular disease risk factor reduction in older adults is presented, as is the importance of considering whether the benefits outweigh the risks in this heterogeneous population.
Comparative effectiveness studies of medications to treat diabetes in older adult populations are lacking. Type 2 diabetes is also characterized by defects in β-cell function that may become more manifest later in life.
The safety of therapies in older adults with diabetes is important to consider in clinical practice to minimize polypharmacy and potential adverse side effects. Meneilly et al. Over 2. However, sitagliptin appeared to have neutral effects on cardiovascular risk compared with placebo without any significant safety concerns.
As the problem of diabetes among older adults grows, so too does the cost of providing diabetes-related care. Inthe ADA estimated that the total costs of diagnosed diabetes in popu,ation U.
The majority of these costs were via Medicare which provides coverage to older adults and Medicaid Also, a large portion of these diabetes-related costs involves treating diabetes-related complications, which are more frequent in older adults with diabetes.
In the article by Choi et al. In parallel, out-of-pocket pharmacy expenses decreased by Future strategies to reduce this coverage gap could have particular benefits for older adults with diabetes.
The prevalence of diabetes in hospitalized patients represents a growing concern. Older adults have a more than three times higher prevalence rate of diabetes compared with younger adults who are discharged from hospitals in the U.
In the Perspective by Umpierrez and Pasquel 30the authors highlight the potential risks of hyperglycemia for older patients in the hospital, including longer length of stay and increased mortality.
Additionally, they emphasize that inpatient glycemic targets should be individualized and that insulin is the preferred treatment for older patients hospitalized with diabetes. A smooth transition to outpatient diabetes care is critical and facilitated by appropriate education in skills for home self-management.
The quality of care offered to patients with diabetes in the inpatient setting is also an important concern. Novel methods to anx inpatient quality of care were investigated by Pogach et al. Among almostpatients receiving therapy for diabetes other than metformin with at least one significant medical, neurological, or mental health condition, approximately half of those aged 65 years and over were OOR by this measure, with overtreatment being much more common than undertreatment.
There was significant variation in facility-level rates for OOR, suggesting that this measure may help focus quality improvement efforts for hospitalized patients with diabetes.
However, Bloomgarden et al. As outlined above, we as a medical community continue to struggle with how best to manage diabetes in older adults.
In large measure, the difficulty results from having continued gaps in research that investigates diabetes in older adults, the age-group with the highest prevalence rates of diabetes and the fastest growing segment of the population.
We also recognize that given the exclusion of older participants from most traditional randomized controlled trials of diabetes interventions, treatment decisions are often made with much uncertainty and need to be individualized.
Therefore, future research should allow and account for the complexity of older adults. Beyond broadening the inclusion criteria for randomized controlled trials, we will increasingly need comparative effectiveness studies to assess safety and efficacy of therapies in older adults with diabetes who are particularly vulnerable to adverse effects from overtreatment.
Older adults with diabetes are a heterogeneous population ranging from the robust to the frail and represent unique challenges and considerations for both the clinician and researcher that will need to be urgently addressed in the future.
On the basis of the considerations cited above and the goal of Diabetes Care to disseminate the latest on this topic, we are proud to feature this special issue devoted to this most complicated topic.
See accompanying articles, pp. is supported in part by National Institutes of Health NIH grant 1UGM, which funds the Louisiana Clinical and Translational Science Center, and NIH grant PAT was supported, in part, by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases RDK Duality of Interest.
has served as the principal investigator of research studies awarded to his institution by AstraZeneca, Janssen, Lexicon Pharmaceuticals, and Sanofi and has served as a consultant for Sanofi, Adocia, Mitsubishi Tanabe Pharma, and Intarcia Therapeutics.
No other potential conflicts of interest relevant to this article were reported. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search.
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: Diabetes and the elderly population| Diabetes and Seniors | The effects of lifestyle, dietary dairy intake and diabetes on bone density populatjon vertebral deformity popultion Diabetes and the elderly population EVOS study. Kalyani RR, Golden SH, Cefalu WT. Lipscombe LL, Jamal SA, Booth GL, Hawker GA. Diabetes Ther ;— A randomized controlled trial of basal-bolus injection therapy vs. Birkeland KI, Jørgensen ME, Carstensen B, Persson F, Gulseth HL, Thuresson M, et al. |
| Top bar navigation | This study found that complications associated with diabetes are costly and vary by condition among Medicare beneficiaries 65 or older with type 2 diabetes. The most common complications were kidney disease, congestive heart failure, and stroke. These three conditions accounted for nearly half of the total cost. Researchers looked at the annual cost of diabetes complications among older adults with type 2 diabetes. They estimated the annual per-person cost of each complication from to and the total cost of all diabetes complications in by using data from Medicare, a national health insurance program primarily for people 65 or older. Policy makers, public health professionals, and researchers can use the findings to evaluate and support health programs that help prevent, delay, or manage diabetes complications. Skip directly to site content Skip directly to search. Español Other Languages. Read about common medication barriers for seniors. The recommended targets for the elderly are the same as for the general population. The recommended fasting blood glucose target blood glucose before a meal for the frail elderly is 5. Elderly people are at higher risk of hypoglycemia. In fact, aging is a risk factor for severe hypoglycemia blood glucose levels that are lower than 2. Common symptoms of hypoglycemia in the elderly include:. Some of the more common factors that can cause hypoglycemia include:. Some symptoms of low blood glucose sugar , such as confusion and disorientation, can be mistaken for other age-related conditions, such as dementia. Family members and caregivers should also be taught how to recognize the signs of hypoglycemia and treat it. Read our expert blog about supporting someone who is at risk for hypoglycemia. If you are having trouble beginning an exercise routine, consider starting off slowly, for example 10 minutes per day of moderate-to-vigorous exercise and work up gradually to minutes of exercise per week. Look for walking clubs in your community. If you have never been physically active, you may want to talk with your healthcare team before you incorporate exercise into your daily routine. They can help you figure out an exercise program that is safe and appropriate for your physical health. Learn more about diabetes and exercise for seniors. If financial concerns are preventing you from being able to obtain required medications and supplies, appropriate nutrition or other diabetes services, there may be some provincial financial assistance programs available specifically for senior citizens. Ask your healthcare team about programs and services in your area that are available to help you manage your diabetes. Find a diabetes support group in your community if you are concerned about your emotional health — feeling overwhelmed, lonely or depressed. Your diabetes healthcare team can refer you to these resources in your area. You can also check out the Emotional Support articles and blogs. Read more about loneliness and diabetes. Ask someone to help you to get to your diabetes-related health care appointments. Some communities provide free or low-cost transportation services to seniors who are no longer able to drive. These data show the need for proper management strategies for elderly patients with diabetes. Management of diabetes in this vulnerable population requires a comprehensive approach that acknowledges the unique challenges faced by older adults. The American Diabetes Association recommends screening for geriatric conditions such as polypharmacy, cognitive impairment, depression, urinary incontinence, falls, persistent pain, and frailty as they may affect diabetes self-management and diminish quality of life [ 3 ]. Multiple comorbidities due to age-related changes in metabolism, reduced physical activity, and cognitive decline may complicate diabetes management. Diabetic complications can be more severe in older people, leading to increased risk of cardiovascular diseases, kidney problems, neuropathy, and visual impairment [ 4 ]. Interactions between medications for different health conditions also need to be considered to avoid adverse effects [ 5 ]. Consequently, these complications and comorbidities may impact individual independence, overall health, and healthcare costs. Elderly people may face difficulties in adhering to complex diabetes management due to limited mobility, financial constraints, or lack of social support; this can lead to unhealthy lifestyle habits. Moreover, health disparities are of greater concern in the elderly. The target goals for glucose control in the elderly should be individualized based on factors such as overall health status, life expectancy, coexisting medical conditions, cognitive function, and functional abilities. For most elderly individuals, a less stringent HbA1c target is often recommended compared to younger adults with diabetes. Preventing hypoglycemia is critical in elderly patients due to blunted hypoglycemia awareness and the potential serious consequences, such as falls, confusion, and cardiovascular events. Advancements in medical technology and the growing fields of personalized medicine and remote monitoring offer promising avenues for tailoring diabetes management to individual needs. For example, continuous glucose monitoring systems and connected insulin pens can facilitate real-time data tracking, allowing healthcare providers to make data-driven treatment decisions for better outcomes [ 7 ]. This may aid in preventing acute hyperglycemic complications and hypoglycemia, which is often neglected in elderly people. However, evidence on the efficacy of these new technologies in older patients is limited. For patients with frailty and immobility, telemedicine and virtual consultations might enable regular checkups, medication adjustments, and lifestyle counseling by reducing barriers to access and increasing adherence to treatment, although its benefit in clinical outcomes needs further clarification [ 8 ]. Also, developing geriatric-focused diabetes education programs can empower them with knowledge and skills to self-manage their diabetes. These programs should focus on diet and exercise capacity and should consider cognitive and learning abilities in older adults. A holistic approach to diabetes management involving a multidisciplinary team of healthcare professionals can ensure comprehensive support for elderly patients. Investing in public health initiatives targeting the prevention and early detection of diabetes in the elderly can have a significant impact on reducing the burden of the disease, especially because a considerable proportion of the elderly with diabetes are unaware of their disease status. Collectively, managing diabetes in the elderly population demands a personalized, evidence-based, and multidimensional approach. It is essential that both healthcare systems and society support the elderly population to receive appropriate care for better controlled diabetes and enhanced quality of life. NOTES CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. |
| Introduction | elcerly ADA Continuous glucose monitoring for diabetes Books Edlerly Compendia Clinical Compendia Home News Body image self-perception News DiabetesPro Elcerly. Rattarasarn C, Soonthornpan Wlderly, Leelawattana R, Setasuban W Decreased insulin secretion but not insulin sensitivity in normal Popularion tolerant Thai subjects. Glycemic targets for T2D in older patients There are few studies specifically addressing optimal glycemic goals in older patients. Dybicz SB, Thompson S, Molotsky S, Stuart B Prevalence of diabetes and the burden of comorbid conditions among elderly nursing home residents. International journal of endocrinology. The international journal of behavioral nutrition and physical activity 7: Permissions Icon Permissions. |
Diabetes and the elderly population -
As Asians and NHPIs age, practitioners must be acutely aware of the duration of their diabetes, which may be more prolonged in these ethnic groups, and tailor glycemic targets and interventions appropriately. In NHPIs, an effective educational strategy may be prudent given their average lack of education compared to other ethnic groups.
One study, in fact, indicated that AAs and Hispanics were more likely to follow exercise recommendations from a healthcare professional than other ethnic groups [ 47 ]. Promoting de-acculturation which advocates eating more fresh foods from their native country and less "Western" style foods has also been successful with Mexican-Americans [ 48 - 50 ].
These lifestyle interventions must be culture-appropriate, as a cross-sectional analysis of the SHIELD US survey showed that despite a similar percentage of respondents from different racial groups receiving exercise recommendations from a healthcare professional, there were large racial differences in the actual implementation of these recommendations [ 47 ].
Most importantly, further studies on the impact of ethnicity on diabetic treatment therapeutics and detailed pharmacogenetic studies are needed, as "one size" may not fit all in diabetes management.
Identifying, recognizing, and then implementing culturally-specific interventions is paramount to good clinical care. There are many potential etiologic reasons for the increase in T2D prevalence with advancing age.
These include lifestyle and cultural factors obesity and sedentary lifestyle , [ 52 , 53 ] potential age-related changes in insulin action and secretion, [ 54 ] inflammatory and hormonal dysregulation, [ 55 , 56 ] genetic factors, [ 57 ] changes in sleep pattern, [ 58 , 59 ] increased oxidative stress, [ 60 ] and increased use of medications that increase hyperglycemic propensity [ 61 , 62 ].
A number of different organ systems and tissues are therefore affected during the aging process with profound ramifications on diabetes risk Figure 1. Figure 1 Changes in hepatic, skeletal muscle, pancreas and adipose tissue during the aging process.
View Figure 1. Obesity is an important cause of both insulin resistance IR and impaired beta β -cell function, the two major factors leading to T2D [ 6 ], and the risk of developing poor glycemic control increases linearly with body mass index BMI [ 63 , 64 ].
The close positive association of BMI with T2D risk, insulin dependence, and macro vascular and micro vascular complications was recently shown in a continuous longitudinal survey of Medicare beneficiaries from [ 65 ].
m2 compared to normal weight individuals, insulin-dependence was five times higher, and the risks of CVD, cerebrovascular disease, renal, and ocular complications were 1.
Compared to other age groups, older adults are the most sedentary [ 68 ]. Greater sedentary time was also associated with increased all-cause mortality. Despite the increased prevalence of T2D in older adults, the fundamental effects of the aging process itself on insulin sensitivity remain relatively unexplored, with the limited available data supporting divergent conclusions.
Insulin resistance is broadly defined as a subnormal biological response to normal insulin concentrations, but in clinical practice typically refers to a subnormal glucose response [ 71 ].
It manifests as the inability of insulin to adequately stimulate peripheral tissue mainly skeletal muscle glucose uptake and suppress hepatic glucose production. Although some studies have reported that older patients have increased insulin resistance [ 72 - 75 ], others have found that aging does not per se cause significant insulin resistance [ 76 , 77 ].
These discrepant results may be related to differences in physical activity level and body composition among study populations [ 78 ]. Of note, prominent risk factors for sarcopenia include both obesity and insulin resistance [ 80 ], and insulin sensitizing agents significantly reduce loss of fat free mass in obese insulin resistant subjects [ 81 ].
A direct causal relationship between insulin resistance and sarcopenia however is uncertain. In some obese individuals, muscle mass is much lower than expected, a condition termed 'sarcopenic obesity'.
This syndrome is accompanied by changes in muscle fiber type [ 82 ], fatty infiltration [ 83 ], and reduced muscle strength [84]. These changes are at least partly attributable to inflammatory mediators and resultant lipotoxicity [ 85 , 86 ].
On a cellular metabolic level, common obesity-associated derangements in mitochondrial function, endoplasmic reticulum ER stress, lipid deposition, and stress-related pathways appear to converge in both insulin resistance and sarcopenia [ 87 , 88 ], but the capacity for glucose utilization remains an undetermined component of the sarcopenia syndrome.
Whether increased adiposity and loss of muscle mass as evident in 'sarcopenic obesity' provide a complete explanation for any observed age-related increases in insulin resistance is unclear.
However, even when study populations are matched for physical activity level and percent lean body mass, results have not been consistent.
Older individuals evaluated by the hyperinsulinemic-euglycemic clamp, the gold standard for assessment of insulin sensitivity, may or may not have reduced peripheral glucose uptake [ 89 , 90 ].
The ability of insulin to suppress hepatic glucose production i. hepatic insulin sensitivity in elderly subjects has been evaluated in a small number of studies mainly involving healthy, normal weight patients [ 72 , 91 , 92 ].
Again, these publications have yielded contradictory results with studies showing greater [ 91 ], no difference [ 92 ], or less [ 91 ] insulin-mediated suppression of hepatic glucose production in the older patient population.
Changes to pancreatic morphology with aging were first noted in the 's [ 93 ]. Cellular senescence of pancreatic β-cells has since been implicated in the pathogenesis of T2D. The aging pancreas exhibits definite defects in β-cell mass [ 94 ], as β-cell proliferation is reduced in aging humans [ 95 , 96 ].
Whether this translates into a decline in β-cell function is controversial. In humans, disorderly insulin release, a decrease in insulin pulse amplitudes, and decreased response to glucose oscillations as well as alterations in insulin clearance have all been observed [ 97 ], which may be related to a loss of pancreatic β-cell GLUT2 expression in humans [ 98 ] as well as differences in β-cell glucose oxidation [ 99 ].
However, in a study of young ages vs. older ages adults, the older patients had greater defects in insulin secretion only in the presence of impaired glucose tolerance or frank T2D.
This suggests that there may not be a strict decline in β-cell function with aging, but this decrement may manifest solely in those with existing dysregulation of glucose homeostasis. Aging is a biological process that is characterized by a decline in basic metabolic processes.
According to the free radical theory of aging, reactive oxygen species ROS can elicit damage to cellular proteins, nucleic acids, and lipids and ultimately lead to age-related organ dysfunction [ ].
ROS produced by the mitochondrial respiratory chain damage mitochondrial proteins, lipids and DNA, and accumulated insults during a lifespan lead to a decline in the bioenergetic function of mitochondria [ ]. Experimental evidence indicates that oxidative stress is an important mechanism for the development of not only T2D, but also the metabolic syndrome, CVD, and nonalcoholic steatohepatitis NASH [ - ].
The role of oxidative stress in T2D is rapidly evolving. As a direct result of the activation of the oxidative stress cascade, insulin signaling is disrupted through serine phosphorylation of insulin receptor substrate IRS proteins [ ]. In addition, ROS can directly affect systemic inflammation and the expression of the anti-inflammatory factor adiponectin, as plasma markers of oxidative stress correlate negatively with circulating adiponectin levels [ ].
We have previously shown that older compared to younger mice fed a high-fat diet HFD have reduced glucose tolerance, advanced atherosclerosis, and pathologic changes resembling human non-alcoholic steatohepatitis NASH largely due to excess oxidative stress and generation of ROS with loss of antioxidant enzyme capacity, and that this effect can be reversed by insulin sensitizing agents [ ].
These results indicate that chronic overproduction of redox signaling pathways, leading to excess oxidative stress and ROS generation may contribute to cell aging and act as an important mediator in dysglycemia.
To summarize, the pathogenesis of T2D in the elderly is multifactorial. The obesity epidemic is a major contributing factor to the rising prevalence of T2D, as excess adiposity is associated with insulin resistance and inadequate β-cell function.
It is unclear; however, if aging has an independent effect on these two major factors and whether changes to muscle composition resulting in 'sarcopenic obesity' is a major driver of dysregulated metabolism. While it is clear that important changes to numerous organs including skeletal muscle, pancreas, liver and adipose tissue occur with aging, their relative contributions to the rising prevalence of T2D in elderly patients remains uncertain.
Most importantly, well-designed trials of weight loss specifically in the older patient population will shed light on the benefits and drawbacks of intervening in this vulnerable group.
Activation of proinflammatory pathways leads to the secretion of numerous cytokines [ ] which induce changes in gene expression that can directly impair insulin signaling and glucose uptake [ ].
Aging is the most prominent risk factor for a myriad of obesity-related chronic diseases including T2D, Alzheimer's disease, frailty and sarcopenia, CVD, fatty liver and steatohepatitis, and certain forms of cancer.
A common feature that links these age-related conditions is chronic inflammation, a process that has been termed 'Inflammaging' [ , ].
Individuals over the age of 65 have increased serum levels of multiple pro-inflammatory factors including interleukin IL -6, IL-1β and IL and tumor necrosis factor-α TNF-alpha [ , ]. Although a complete discussion of the role of inflammation in the aging process and its contribution to age-related declines is beyond the scope of this review see the comprehensive review by Goldberg, et al.
Acting as the body's primary long-term energy reservoir, adipose tissue AT is now recognized as the largest endocrine organ, secreting over fifty metabolically-active adipokines, cytokines, and chemokines [ ]. In fact, the early stages of systemic inflammatory gene expression are selectively induced in AT, rather than liver and skeletal muscle [ ].
Weight gain occurs when caloric intake exceeds energy expenditure, resulting in adipose tissue expansion to accommodate increased energy storage demands.
In obesity, excessive expansion substantially alters adipose tissue histology and function. As adipocytes enlarge, some become apoptotic and are surrounded by macrophages to form crown-like structures, a hallmark of adipose inflammation [ ].
Interactions among adipocytes and adipose immune cells at different stages of this process enhance pro-inflammatory and suppress anti-inflammatory immune cell accumulation and production of metabolically-active mediators.
A comprehensive, balanced system of pro- and anti-inflammatory mediators and immune cells is required to maintain normal adipose storage, endocrine function, and systemic insulin action, all critical to whole body metabolism [ ].
Recent, transformative animal studies highlight the importance of several immune cells in maintaining lean adipose tissue, creating a shifting paradigm in obesity research.
Eosinophil-derived interleukin IL -4 promotes the differentiation and maintenance of T h 2s, T regs , and AAMacs. Accordingly, eosinophil-deficiency leads to high-fat diet HFD -induced insulin resistance, while IL-4 deficient mice are rescued in proportion to the number of adoptively-transferred wild-type eosinophils entering into adipose tissue [ ].
IL and IL also rapidly activate ILC2s [ ] to produce IL and IL-5 that further promote adipose tissue eosinophil and M2 ATM accumulation, [ ] and lead to activation of iNKTs [ , ].
Adoptive transfer of iNKTs into obese mice induces weight loss and improves glucose tolerance in a cytokine-dependent manner [ ]. Thus, a newly defined ILC2-eosinophil-NKT axis helps maintain lean mice AT metabolic homeostasis; but this axis has yet to be explored in humans.
Figure 2 Inflammatory regulation in lean and obese adipose tissue. Recent animal studies highlight the importance of several immune cells in maintaining lean adipose tissue.
In this context, the normal architecture, energy storage, and endocrine activities of adipocytes are changed. Abbreviations: Sfrp5: Secreted frizzled-related protein 5.
Figure reproduced with permission from Annual Reviews of Pathology [ ]. View Figure 2. In obesity, the immunologic milieu of adipose tissue shifts from a cytokine-associated type 2 anti-inflammatory to a type 1 pro-inflammatory environment.
In this context, the normal architecture, energy storage, and endocrine activities of adipocytes are profoundly altered as they accumulate triglycerides and become hypertrophic. In fact, adipocytes may initiate the cascade of adipose tissue inflammation, as they link storage capacity and endocrine function and are the predominant source of adiponectin, leptin, and other key mediators [ ].
Leptin has multiple pro-inflammatory effects and increases soon after exposure to nutrient excess. Both leptin and MHCII expression promote T h 1 cell polarization and activation, since adipose inflammation is markedly attenuated in both leptin- and MHCII-deficient obese mice [ ].
The effects are also opposed by IL-4 and from T h 2 and T reg cells [ ]. Emerging evidence highlights the importance of T regs in defining the immunologic milieu of lean and obese AT.
In the lean state, the stability of T regs is enhanced by IL [ ], a potent adipocyte-derived anti-inflammatory cytokine that is also produced by anti-inflammatory macrophages and T lymphocytes. Furthermore, adiponectin decreases MHCII expression which is required by antigen presenting cells APCs to increase T reg abundance [ ].
Adipose tissue T regs also regulate systemic insulin action and strongly inhibit pro-inflammatory responses of other T cell subtypes. Insulin-sensitizing PPARγ ligands increase adipose T reg content, while T reg -specific PPARγ deficiency impairs ligand-induced insulin sensitivity [ ].
Adoptive transfer of T regs to obese, insulin-resistant mice improves insulin action, underscoring the role of T regs in insulin sensitivity [ ]. In humans we found not only that adipocyte MHCII up-regulation occurs in obesity [ ], but expression of adipose tissue T reg markers decrease, and expression of T h 1 markers and IFNу increases [ - ].
Of relevance to the aging process, the VAT T reg pool decreases with advancing age in animal models [ ]. This finding has yet to be replicated in humans and a subsequent study demonstrated that mice deficient in AT T regs are protected against age-associated insulin resistance [ ].
If confirmed, the decrease in T regs may be due to reduced IL [ ]. Recently, IL was identified as an indispensable factor for the development and maintenance of VAT T regs , since genetic ablation of IL or its receptor severely reduces adipose T reg abundance [ ].
IL thus has important actions on both T regs and ILC2s, and has emerged as a central regulator of cells that limits inflammation in lean AT. Therefore, further human studies are needed to clarify the role of T regs in human aging and determine whether these immunometabolic AT changes contribute to higher rates of T2D during the human aging process.
A number of complications and geriatric syndromes are more common in patients with T2D. The risk of nephropathy is doubled. T2D also accelerates CVD [ , ], the primary cause of mortality in T2D patients. The risks of retinopathy and macular degeneration the two primary causes of blindness are both higher in the diabetic population.
Depression is independently associated with poor glycemic control [ ]. Disabilities in activities of daily living ADL's are 1. Older diabetics also have a two-fold inability to climb stairs and an increased risk of falling.
Polypharmacy is an important risk in this patient population and this risk is increasing over time. With an aging population, there has been an alarming increase in the prevalence of cognitive dysfunction including dementia. The metabolic syndrome including central obesity has been associated with the risk of cognitive decline, overall dementia and vascular dementia [ ].
The presence of insulin resistance IR , in itself, has been linked to an increased risk of mild cognitive impairment MCI [ ] and the degree of IR negatively correlates with tests of cognitive function and brain preservation by imaging [ ].
Insulin has direct effects on the brain; affects the production, degradation and clearance of β-amyloid leading to plaque deposition [ ] and plays a pivotal role in the phosphorylation of tau to form neurofibrillary tangles, which are implicated in Alzheimer-associated dementia [ ].
In addition, insulin and hyperglycemia have direct effects on the vasculature, increasing the risk of vascular cognitive impairment and vascular dementia. A recent meta-analysis demonstrated significant improvement in memory and executive function after weight loss [ ].
No other recently published study examined the post-surgical impact of bariatric surgery on cognition using a neuropsychometric test battery but was performed in middle-aged subjects. Gunstad, et al. analyzed data from bariatric surgery patients mean age Compared to controls, surgical patients had improved memory performance and executive function, raising the possibility that large-scale weight loss with bariatric surgery may have a protective effect on cognition in older obese individuals; a critical yet untested outcome measure.
There are few studies specifically addressing optimal glycemic goals in older patients. The vast majority of the available data derives from younger and middle-aged Type 2 diabetic patients and may not necessarily be applicable to older patients.
The American Diabetes Association ADA Consensus Development Conference on Diabetes and Older Adults in admitted that "There are essentially no directly applicable clinical trial data on glucose control for large segments of the older diabetic patient population" [ , ].
Neither the ADA nor the U. Department of Veteran Affairs and the U. In fact, one of the major obstacles in determining therapeutic options in an older patient group is the lack of glycemic targets based on varying age and comorbid subgroups. We recognize that subdividing older patients by age may a useful component in establishing such targets, but the literature is devoid of studies using this approach although they may indirectly utilize age grouping as a criterion by taking into account life expectancy , and this approach is somewhat limited by the extreme differences in functional status, body composition, comorbidities, etc.
that exist in older patients of the same chronologic age. Elderly individuals with T2D fall generally into two predominant categories: those who acquire the condition in middle age and those who acquire T2D later in life i.
middle-aged onset diabetes and elderly- onset diabetes [ ]. The vast majority of older patients with T2D are middle-aged onset and these patients suffer a greater burden of microvascular disease and are at higher risk for inferior glycemic control [ , ].
Despite these differences, however, the limited evidence that underlies our current treatment approaches does not take diabetes duration into account. In addition, although macrovascular disease appears to be related to age at diabetes onset, it is unclear if this is an important factor for the development of CVD [ ].
In determining glycemic targets in older patients, it is important to devise strategies that not only limit hyperglycemia which can increase complication risk, lead to dehydration, and create vision and cognitive changes which can increase fall risk; but also limit hypoglycemia which can also increase the risk of CVD [ ], cognitive impairment [ ] and falls.
In addition, adding anti-diabetic medications can contribute to polypharmacy. Most of the available proposed guidelines are ultimately based upon an individual's overall health and projected life expectancy [ , ].
Since studies have demonstrated that ~8 years are required before the benefits of improved glycemic control are reflected in decreased microvascular complications, a frail, older patient with 10 year life expectancy without complications would benefit from more stringent control i.
HgBA1c Table 1: Consensus framework for considering treatment goals for glycemia in older adults with diabetes. Adapted with permission from American Diabetes Association Older Adults. Section In Standards of Medical Care in Diabetes - Diabetes Care ; 39 Suppl.
View Table 1. In summary, the lack of available evidence-based guidelines for large segments of the elderly diabetic population is a major impediment to providing optimal clinical care. Large, randomized trials specifically in older adults are necessary to better refine an individual's glycemic control targets and to tailor treatment accordingly.
In addition, trials of older patients with certain phenotypic characteristics and specific comorbidities must be performed to ascertain if the results found in younger adults can be properly translated to elderly patients. The treatment of T2D in older patients must be individualized not only to ensure effectiveness, but to maximize patient safety and quality of life.
Treatment options generally fall into 3 categories. Lifestyle modification: The effectiveness of standard lifestyle intervention in weight management and glycemic control has been largely unsuccessful due to poor patient adherence and long-term sustainability. In the UKPDS, for example, all patients were advised to follow a low calorie, low fat, high complex carbohydrate diet in addition to regular physical exercise as recommended by the ADA [ ].
Sustained weight loss has also been difficult to achieve with health care provider dietary and physical activity advice.
As an example, a meta-analysis of behavior intervention diet and exercise recommendations trials failed to show significant weight loss compared to controls [ ].
In contrast, a well-designed and more intensive lifestyle intervention has been shown to be an effective weight loss strategy and improve glucose homeostasis [ ].
Data from the recent multicenter Look AHEAD Action for Health in Diabetes trial found that intensive lifestyle intervention initial weekly meetings to discuss reduced-calorie kcal diet, use of meal replacements, decreased fat intake to ]. However, the average age of the participants in the Look AHEAD study was Despite the above findings, there is evidence that older patients can respond positively to lifestyle interventions, and age should not in itself be a deterrent to improving one's lifestyle.
In an RCT tailoring nutrition to the individual's medical, lifestyle, and personal factors called Medical Nutrition Therapy MNT , the intervention group had greater improvements in fasting glucose and HgBA1c levels [ ].
The effect of differing dietary macronutrient composition on metabolism and glycemic control in younger versus older individuals is largely unknown. The American Diabetes Association ADA recommends both nutrition therapy and exercise as non-pharmacological cornerstones in the management of T2DM.
Despite these recommendations, beneficial effects in both diabetic and non-diabetic subjects, including improved glycemic control and greater weight loss, have been observed by increasing dietary protein and lowering carbohydrate intake [ - ]. Data from several studies conducted in patients with T2DM have found specific benefits of low-calorie diets that contain increased protein and decreased carbohydrate than low-calorie diets with higher carbohydrate content, including a protein-mediated increase in insulin secretion [ ] and greater decreases in body weight, HgbA1c and use of diabetes medications [ ].
These studies, however, were all conducted in young to middle-aged adults. Short-term studies - ] but longer-term studies are needed and current guidelines do not distinguish by patient age. Older adults with T2D, in particular, are at risk for greater loss of muscle strength compared to younger patients and may benefit from increased protein intake, but studies are limited.
The metabolic effects of altering dietary composition in an elderly population and their role in preserving lean mass, especially muscle mass, is thus relatively unknown and requires further investigation.
The effect of differing exercise regimens and diet on cognitive function in older individuals and their relationship to metabolic improvements remains controversial. There is clear evidence that physical activity can contribute to healthy aging and reduce morbidity and mortality [ , ].
Yet there are only a limited number of studies, with small population sizes, addressing the effect of exercise in tertiary prevention of cognitive decline in those with existing dementia [ , ]. Research on the effect of dietary modification to prevent cognitive decline is also in its infancy and the benefits of changing macronutrient content is oftentimes difficult to separate from their effects on associated comorbidities such as obesity, diabetes, and CVD [ ].
One of the major limitations in our current knowledge is the lack of established guidelines and evidence-based studies for exercise and diet in older patients with T2D.
These same guidelines advise older adults to increase their activity to minutes of moderate-intensity or minutes of vigorous-intensity exercise per week combined with muscle training activities [ ].
However, recommendations specific for an older type 2 diabetic patient are lacking. The ADA, for instance, endorses a similar amount of exercise in diabetics as the CDC does for the general population aged 18 to 64, but provides no specific exercise recommendations in those over the age of 65 [ ].
In addition, the ADA has very generalized guidelines for dietary caloric content and macronutrient composition in Type 2 Diabetics, does not set an ideal percentage of calories from carbohydrates, protein, or fat, and does not dictate specific recommendations based on patient age [ ].
Drug therapy for T2D in older patients: There is a paucity of data related to specific drug therapy in older patients with T2D [ ]. Hypoglycemia in older individuals is associated with significant morbidities leading to both physical and cognitive dysfunction, and recurrent hospital admissions due to frequent hypoglycemia are associated with further deterioration in patients' general health that can eventually lead to frailty and disability [ ].
Patients with dementia are four times more likely to be admitted for hypoglycemia episodes compared to those with normal cognition [ ]. Severe hypoglycemia can result in acute vascular complications including stroke, heart failure and arrhythmia [ ].
In addition, the brain is dependent on glucose and is exquisitely vulnerable to the effect of hypoglycemia. After a single hypoglycemia event, cognitive changes occur, and recurrent hypoglycemia leads to a graded increased risk of dementia with each subsequent hypoglycemic episode [ ]. Given that the risk of hypoglycemia is also increased by folds in obesity, the inter-relationship between T2D, obesity, cognitive dysfunction and hypoglycemia during aging must be given consideration in determining a safe treatment regimen.
Table 2: Non-Insulin pharmacotherapy options for Type 2 Diabetes Mellitus in the elderly. Listed medications are limited to those commercially available in the U. at time of manuscript submission. View Table 2.
According to the most recent ADA guidelines, metformin a biguanide is considered first-line therapy in T2D [ ]. Given its low hypoglycemic risk profile and low cost, metformin may also be beneficial in older adults.
However, limitations to its use include side effects predominantly gastrointestinal , weight loss which may preclude its use in frail patients, and a small risk of lactic acidosis in patients with renal dysfunction. Sulfonylureas are also cost-effective, but are limited by hypoglycemia that may be problematic for older patients, especially those with reduced glomerular filtration capacity or poor appetites.
The shorter duration glipizide and the glinides repaglinide and nateglinide may be preferable in this scenario; but overall the risk of prolonged hypoglycemia with all sulfonylureas and glinides makes their use largely inadvisable in the elderly population.
Alpha-glucosidase inhibitors such as acarbose specifically target post-prandial hyperglycemia and have low hypoglycemia risk; however, gastrointestinal side effects, frequent dosing, and relatively low efficacy may limit their applicability in some older patients.
Thiazolidinediones pioglitazone and rosiglitazone improve sensitivity to insulin predominantly by binding to the PPARγ receptor. However, they have been associated with weight gain, edema, heart failure, bone fractures, and bladder cancer, precluding their use in certain older adults.
Dipeptidyl peptidase-IV DPP-4 inhibitors sitagliptin, linagliptin, saxagliptin, and alogliptin preferentially target post-prandial hyperglycemia, carry limited hypoglycemic potential, and are generally well tolerated. This suggests that they may be useful for older patients; but applicable prospective studies are limited.
A recent retrospective observational study focused on the safety and tolerability of the DPP-4 inhibitors in type 2 diabetics aged 65 years and older.
Additionally, patients on DPP-4 inhibitors showed a reduction in HgBA1c from approximately 8. Among patients receiving DPP-4 inhibitors identified in this study, most patients were taking sitagliptin In addition, no significant differences were noted in the HgBA1c-lowering effects of these agents between elderly and younger patients.
Glucagon-like peptide-1 GLP-1 receptor agonists twice daily exenatide, once daily liraglutide, once weekly exenatide XR, dulaglutide, and albiglutide are also useful in preventing post-prandial hyperglycemia and impart low hypoglycemic risk. They can promote weight loss, and at higher doses, liraglutide is approved for weight reduction independent of diabetes status.
However, they can cause nausea, promote weight loss, and are injectable therapies and thus may not be ideal for frail patients or those with vision, sensory or hearing impairment. Both the DPP-4 and GLP-1 receptor agonists also require dose reductions with kidney dysfunction and are largely unstudied with coexistent hepatic impairment.
Sodium-glucose co-transporter-2 SGLT2 inhibitors canagliflozin, empagliflozin, and dapagliflozin are newer oral diabetes medications, but there experience in older adults is unknown. Their use may also be limited by side effects dehydration, increased thirst, polyuria , increased risk of genital and urinary tract infections and reduced effectiveness in patients with preexisting kidney disease.
Insulin therapy can be used successfully in select older adults with T2D, and generally have similar efficacy and hypoglycemia risk compared to younger patients. The biggest limitation is the potential for hypoglycemia and this risk must carefully be assessed in an individual older patient. A separate study demonstrated that long-acting insulin in older patients mean age 69 years old with T2D did not increase the risk of hypoglycemia compared to younger patients [ ].
In addition, vision impairment and limited manual dexterity may be barriers to insulin therapy compliance for some older adults. Bariatric surgery as a treatment modality in obese older patients: Nearly half of adult patients with T2D fail to achieve adequate glycemic control with medication and lifestyle modifications alone.
In contrast, marked weight loss following bariatric surgery BS often results in complete remission of T2D [ ]. Conventional bariatric surgery procedures include Roux-en-Y gastric bypass RYGB , laparoscopic adjustable gastric banding LAGB , laparoscopic sleeve gastrectomy SG , biliopancreatic diversion BPD and biliopancreatic diversion with duodenal switch BPD-DS.
Currently, the three most popular bariatric surgical procedures performed in the United States and worldwide are the RYGB, SG and LAGB procedures [ ].
Eligibility criteria for bariatric surgery have been expanded from the original NIH Consensus Conferences of to include individuals up to 60 years of age [ , ]. Although the majority of outcome data related to BS derives from studies of young and middle-aged patients, there has been a discernable increase in the number of older patients undergoing BS [ - ], especially laparoscopic SG.
This increase is likely related to the perceived safety and effectiveness of the SG procedure, with shorter operating times, abbreviated hospital stays, substantial weight loss and remission of comorbidities [ , ].
Despite the increasing popularity of BS, aging is an important negative predictor of diabetes remission following BS [ ].
However, BS can still be successful in older obese patients. Retrospective data of operations, mainly performed by laparoscopy, have shown that older obese adults undergoing bariatric surgery have more baseline co-morbidities and require more medications than younger subjects, but lose clinically significant amounts of weight and have a significant reduction in co-morbidities post-surgery [ - ].
Based on these results it was determined that RYGB is effective in producing marked weight loss in patients over the age of 65 with an acceptable safety profile.
However, the effect of age on BS-induced changes in insulin sensitivity and β-cell function are currently unknown and further studies on the metabolic improvements and limitations of BS in older patients are certainly warranted.
The number of elderly individuals in the U. is growing. Within this rapidly expanding demographic, the rates of T2D and obesity are reaching epidemic proportions. T2D in old age carries an increased risk of the traditional diabetes-associated complications including microvascular and macrovascular disease, but also age-related comorbidities including cognitive impairment, urinary incontinence, sarcopenia, and increased falls.
An overall state of chronic inflammation and dysregulated immunometabolism may underlie these increased risks. Unfortunately, a majority of the clinical trial data related to risk profiles, glycemic targets, and therapeutic interventions for T2D are not applicable for large segments of the older patient population.
Recognition of this knowledge gap is not adequate. We need strong evidence-based data upon which to successfully intervene in a heterogeneous group of elderly patients with T2D.
In order to truly recognize, understand and ultimately treat metabolic disease in older individuals, we must first address several substantial limitations in our fundamental understanding of T2D pathogenesis and treatment during the aging process.
Most importantly, evidence-based data from studies in younger diabetic patients need to either be validated or refuted in older patients to truly individualize diabetic care and ultimately improve patient outcomes. This study was supported by grants from the American Diabetes Association ICTS and the National Institutes of Health KL2 Scholar Award KL2TR This study was supported by grants from the American Diabetes Association ICTS and the National Institutes of Health KL2 Scholar Award.
WH serves on a Scientific Advisory Board for Merck, Astra Zeneca, and NovoNordisk. Join Us Latest Articles Contact. Journal Home Editorial Board Archive Submit to this journal Current issue J Geriatr Med Gerontol ISSN: Abstract Keywords Introduction Manuscript Text Conclusions Acknowledgements Sources of Support Author Contributions Disclaimers Figure 1 Figure 2 Table 1 Table 2 References Download PDF.
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J Geriatr Med Gerontol ISSN: Abstract Keywords Introduction Manuscript Text Conclusions Acknowledgements Sources of Support Author Contributions Disclaimers Figure 1 Figure 2 Table 1 Table 2 References Download PDF Journal of Geriatric Medicine and Gerontology DOI: Abstract In the older patient population, rates of Type 2 Diabetes T2D and obesity are reaching epidemic proportions.
Keywords Type 2 Diabetes Mellitus, Obesity, Elderly Introduction In the last decade alone, the percentage of adults over the age of 65 in the United States U.
Manuscript Text Definition of elderly and old age There is currently no universally accepted age threshold to define the terms "elderly" or "old age. Demographics of T2D in aging The higher prevalence of T2D in older individuals is seen in both men and women and across racial and ethnic groups [ 2 ].
Pathogenesis of T2D in the elderly There are many potential etiologic reasons for the increase in T2D prevalence with advancing age. Complications of T2D in the elderly A number of complications and geriatric syndromes are more common in patients with T2D.
Glycemic targets for T2D in older patients There are few studies specifically addressing optimal glycemic goals in older patients. View Table 1 In summary, the lack of available evidence-based guidelines for large segments of the elderly diabetic population is a major impediment to providing optimal clinical care.
Treatment of T2D in the elderly The treatment of T2D in older patients must be individualized not only to ensure effectiveness, but to maximize patient safety and quality of life. View Table 2 According to the most recent ADA guidelines, metformin a biguanide is considered first-line therapy in T2D [ ].
Conclusions The number of elderly individuals in the U. Acknowledgements This study was supported by grants from the American Diabetes Association ICTS and the National Institutes of Health KL2 Scholar Award KL2TR Sources of Support This study was supported by grants from the American Diabetes Association ICTS and the National Institutes of Health KL2 Scholar Award.
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Horm Res Ryan AS Insulin resistance with aging: effects of diet and exercise. The previously described data argue for a more aggressive approach to risk-factor modification in elderly persons than has previously been applied.
There are few original studies of dietary interventions in elderly patients with diabetes 5. It appears that elderly patients with this illness avoid simple sugars but do not adhere to current dietary recommendations regarding fat and fiber composition.
A dietary intervention that results in weight loss has been found to improve glycemic control in ambulatory obese elderly patients with diabetes.
However, diabetic diets complicate the care and increase the cost of looking after frail elderly nursing-home patients, and these diets do not appear to significantly improve glycemic control in this patient population. Elderly patients with diabetes are at risk for deficiency of trace elements, and magnesium and zinc supplementation results in improvements in glycemic control.
Hyperglycemia in elderly patients with diabetes is associated with increased oxidative stress Small-scale studies have demonstrated that supplementation with antioxidant vitamins C and E may improve glycemic control 5. Unfortunately, the effect of exercise programs on glycemic control in elderly patients with diabetes has been incompletely assessed, and the results of the studies that have been done are conflicting 5.
Clearly, further investigations are needed to evaluate the role of dietary and exercise interventions in the management of diabetes in the elderly population. α-Glucosidase inhibitors act by inhibiting the digestion and absorption of simple sugars from the gastrointestinal tract.
The major side effects of these drugs are gastrointestinal, particularly flatulence and diarrhea. A recent randomized controlled trial of glyburide versus the α-glucosidase inhibitor miglitol in elderly patients with diabetes demonstrated that miglitol reduced Hgb A1C by about 0.
However, the patients who were treated with glyburide had more weight gain, a higher frequency of hypoglycemia, and an increased incidence of cardiovascular events In a recent randomized multicenter trial of the α-glucosidase inhibitor acarbose in obese elderly patients with diabetes, acarbose reduced Hgb A1C by about 0.
α-Glucosidase inhibitors are useful drugs as primary therapy for elderly patients with modest fasting hyperglycemia, especially if they are obese. They can also be used in patients taking other oral agents to enhance glycemic control.
Metformin is currently the only biguanide available in North America. Aging does not appear to be a risk factor for lactic acidosis with metformin, provided that careful attention is paid to the contraindications for this drug significant liver, renal, and cardiac disease 5. Limited nonrandomized clinical studies suggest that the drug is safe and effective as monotherapy in obese older people 5.
A recent randomized controlled trial demonstrated that metformin was also effective when added to glyburide in poorly controlled elderly patients with diabetes. In this study, Hgb A1C was reduced by approximately 1. In our view, metformin is an ideal drug for first-line therapy of obese older patients, because it increases insulin sensitivity, assists with weight loss, reduces lipid levels, and rarely causes hypoglycemia.
In addition, it is a useful adjunct for patients who are inadequately controlled on maximum doses of sulfonylureas. Drugs in this class improve glycemic control by ennhancing peripheral insulin sensitivity. Troglitazone was the first drug of this type released for clinical use. This drug was recently removed from the market because of concerns regarding hepatic toxicity.
A randomized controlled trial of troglitazone in elderly patients with diabetes found that the drug was safe if patients were carefully monitored for hepatic toxicity. Troglitazone resulted in significant improvements in insulin sensitivity and glycemic control Two more drugs in this class have recently been released for use.
There are no data yet available on the effect of pioglitazone in elderly patients. The kinetics of rosiglitazone are not significantly altered in elderly patients Pooled data on elderly subjects from the clinical trials that have been done with rosiglitazone have recently been published in abstract form Rosiglitazone appears to be as effective in older patients as in younger patients and results in an approximate 1.
Hepatic toxicity has not been reported in elderly subjects, although all elderly subjects who are started on rosiglitazone should have liver function tests monitored regularly until further studies are forthcoming.
The incidence of edema and anemia was substantially higher in elderly patients than in middle-aged patients treated with this drug, and volume status and blood count will need to be carefully monitored in patients started on rosiglitazone.
Rosiglitazone can be a useful first-line therapy in obese elderly patients, particularly for those patients who cannot tolerate metformin or have a contraindication to it. The absorption and elimination of glyburide is impaired with age, and elderly subjects appear to have enhanced insulin responses to the drug as well 5.
This may explain, in part, the age-related exponential increase in the frequency of severe or fatal hypoglycemia with this drug. The kinetics of other sulfonylureas do not appear to alter importantly with age 5.
In our opinion the use of chlorpropamide is relatively contraindicated in elderly persons because this drug is associated with an increased frequency of hypoglycemia, and can interact with multiple drugs and cause an antabuse effect and syndrome of inapproriate secretion of antidiuretic hormones, or SIADH.
The risk of hypoglycemia associated with sulfonylureas in aged adults appears to be reduced with tolbutamide, gliclazide, and, possibly, glipizide In addition to the type of sulfonylurea, other potential risk factors for hypoglycemia with these drugs in elderly persons include black race, multiple medications, male sex, renal dysfunction, and ethanol consumption 27 Sulfonylureas should be considered as a first-line therapy in lean elderly patients with diabetes.
Elderly subjects often make errors when trying to mix insulin on their own. The accuracy of insulin injections has been shown to be improved in older patients when they are treated with premixed insulin 5.
Small-scale studies suggest that as long as a premixed insulin is used, the portion of regular to long-acting insulin in the mixture i. Due to compliance problems in older individuals, some clinicians have recommended using one injection of insulin per day.
However, hypoglycemia appears to occur more commonly with one injection rather than two daily injections in this patient population. One study 60 suggested that a combination of a sulfonylurea with insulin is probably more effective than the same dose of insulin alone in elderly patients.
However, another study 61 failed to show a difference from the efficacy point of view between two doses of insulin, one dose of insulin at bedtime plus sulfonylureas, compared with one dose of insulin at breakfast plus sulfonylureas.
In this latter study, weight gain was comparable between groups. Some differences between regimens may have been masked because one third of the patients who were started on one dose of insulin daily needed a second injection to control glycemia. No studies have evaluated the effectiveness of bedtime insulin along with daytime metformin in elderly persons.
Our clinical experience suggests that this strategy is effective in some patients who are reluctant to inject insulin twice a day. We have also had extensive clinical experience with the use of metformin in elderly patients with diabetes treated with bid insulin.
In obese patients, this combination appears to reduce weight gain associated with insulin treatment, reduce insulin requirements, and improve glycemic control. To date, no studies have evaluated the effect of lispro insulin in the treatment of diabetes in elderly patients.
Repaglinide is a nonsulphonylurea drug that has a distinct β-cell binding profile and stimulates insulin secretion from the β cell by a mechanism similar to that of sulphonylureas.
The potential advantage of this drug is that it has a rapid onset and very short duration of action. As a result, it is felt to be of value because it results in a more physiologic insulin profile and because it can be given just before a meal in patients who tend to have irregular eating patterns.
In addition, in younger patient populations, repaglinide has been associated with a lower frequency of hypoglycemic events when compared with conventional sulphonylureas, presumably because of its shorter duration of action. The kinetics of repaglinide are not altered with age Data on elderly subjects from the clinical trials that have been done with this drug has been published in abstract form The drug resulted in a similar change in fasting glucose and Hgb A1C values in middle-aged and elderly subjects, suggesting that it has similar efficacy in each age group.
In addition, when compared with younger patients with diabetes, elderly patients treated with repaglinide had a similar frequency of hypoglycemic events, suggesting that this drug may be associated with a lower frequency of hypoglycemia in elderly persons than conventional sulfonylureas.
Pending the results of properly randomized controlled trials in the elderly population, repaglinide may be considered for elderly patients who have irregular eating habits, or have frequent hypoglycemic events on conventional sulfonylureas.
These potential benefits must be balanced against the cost of the new drug and compliance problems that could result from having to take the drug three times a day. Depression is common in older people with diabetes. A recent randomized controlled trial 64 demonstrated that fluoxetine can assist with weight loss and improve glycemic control in obese elderly patients with diabetes.
This drug should be considered for therapy of depression in obese elderly patients with diabetes, particularly if they are in need of improved glycemic control. Because fluoxetine has a very long half life, caution should be used when administering this drug to older patients, since excessive weight loss could occur before the drug is cleared from the system.
For this reason, fluoxitene should never be given to lean elderly patients with diabetes. Orlistat is the first of a new class of antiobesity agents, the lipase inhibitors, which have been developed for the long-term management of obesity.
This drug acts by selectively inhibiting the absorption of dietary fat. Limited data from studies in middle-aged patients with type 2 diabetes suggest that orlistat can result in clinically meaningful weight loss, improve glycemic control, and improve lipid profile Because elderly persons with diabetes tend to have diets that are high in saturated fat, this drug may prove to be useful in obese patients.
However, there are no data as yet from studies in the elderly population, and caution should be used until further information is forthcoming. Glucagon-like peptide GLP-1 is a peptide hormone secreted from the intestine in response to food ingestion.
This peptide has been shown to enhance glucose-induced insulin release and reduce appetite in middle-aged patients with diabetes. Recent data from our laboratory suggest that GLP-1 maintains its ability to enhance glucose-induced insulin release in elderly patients and may also increase insulin sensitivity and NIMGU G.
Meneilly and D. Elahi, unpublished observations. Long-term clinical studies are required to determine the role of this peptide in the therapy of diabetes in aged adults. No data are currently available on the use of pramlintide in aged adults. Because the renal threshold for glucose increases with age, urine glucose testing is not reliable in aged adults.
Most studies have found that elderly patients can successfully be taught to monitor blood sugar at home, and such monitoring does not alter their quality of life.
Hgb A1C is the standard measure of long-term 2—3 mo glycemic control in this patient population, although serum fructosamine can be used to measure changes in glycemic control over a shorter period 2—3 wk 66 Because of the dramatic increase in its prevalence, diabetes in the elderly population may ultimately prove to be the most important epidemic of the 21st century.
Fortunately, our increased understanding of the pathogenesis and treatment of this illness should allow us to improve the outcome of the large numbers of elderly patients that will be afflicted with this illness. Prevalence of diabetes in men and women in the U.
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Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension.
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Tessier D, Khalil A, Fulop T, Johnston PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL, Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. Meneilly GS, Ryan EA, Radziuk J, et al.
Effect of acarbose on insulin sensitivity in elderly patients with diabetes.
Diabetes is Diabetes and the elderly population one Pancreatic surgery the Diabtees widespread health burning problems in eldedly elderly. Worldwide prevalence of ellderly among subjects over 65 years was million ina number that is Diaebtes to double in Regular meal timetable Old patients with eldrely have a higher risk of common geriatric syndromes, including frailty, cognitive impairment and dementia, urinary incontinence, traumatic falls and fractures, disability, side effects of polypharmacy, which have an important impact on quality of life and may interfere with anti-diabetic treatment. Because of all these factors, clinical management of type 2 diabetes in elderly patients currently represents a real challenge for the physician. Actually, the optimal glycemic target to achieve for elderly diabetic patients is still a matter of debate.
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