Asian Best Practices for Care of Diabetes in Elderly (ABCDE)

The elderly population with diabetes is diverse with the majority experiencing a decline in physical and mental capabilities, impacting the entire diabetes management process. Therefore, a need for geriatric-specific guidelines, especially for the Asian population, was identified and subsequently developed by an expert panel across government and private institutions from several Asian countries. The panel considered clinical evidence (landmark trials, position papers, expert opinions), recommendations from several important societies along with their decades of clinical experience and expertise, while meticulously devising thorough geriatric-specific tailored management strategies. The creation of the ABCDE best practices document underscores and explores the gaps and challenges and determines optimal methods for diabetes management of the elderly population in the Asian region.


Introduction
he elderly population with diabetes is diverse. Some have physical and mental capacities like many younger ones, whereas others experience considerable declines in these capabilities. This impacts the entire diabetes management process. Therefore, it is imperative to address the differences in managing diabetes in the elderly population in a patient-centric manner. To obtain multiple perspectives in this regard, the Asian hybrid steering committee meeting on geriatric diabetes was conducted in Rishikesh, India. The expert panel involved key opinion leaders and representatives of the government as well as private institutions from Afghanistan, Bangladesh, The integration of technological aids, and environmental modulation to facilitate the management of diabetes in the presence of problems unique to the elderly was elaborately discussed and best practices were agreed upon. The consensus was drafted on these principles and circulated among expert panel members for their critical appraisal; it was subsequently amended with appropriate changes. Thus, the aim of the ABCDE to underscore and explore the gaps and challenges and determine optimal methods in diabetes management of the elderly population in the Asian region was achieved.

Elderly in Asia 1.Definition of 'Geriatric
The term "geriatric" has had different definitions over the past decades. A few decades ago, those ≥ 85 years of age were classified as oldest-old. Later, older adults were classified into three groups young-old (65-74 years of age), middle-old (75-85 years of age), and the oldest-old (> 85 years of age). Whereas World Health Organization (WHO) defines older persons as ≥ 60 years of age, most countries usually consider 60-65 years of age as geriatric [1,2]. However, for clinical purposes, rather than classifying older adults based on chronological age, a classification based on functional capabilities is more pragmatic. The functional aspects are influenced by genetics, environmental features, and co-morbidities such as metabolic disorders, hypertension, arthritis, obesity, renal function, and most importantly, cognitive abilities, which indeed reflect the physiological and vascular age. Thus, based on the International Diabetes Federation (IDF) classification the ABCDE experts have appropriately categorized older adults into four groups/categories based on functional capacities, level of medical comorbidities, and degree of frailty, which should guide diabetes management (Table 1) [3].

Prevalence of Type 2 Diabetes Mellitus in Asia
Globally, there were 704 million older adults (65-99 years) in 2019, a number that is projected to increase to 995 million in 2030 and 1.4 billion by 2045. The estimated prevalence of diabetes in this population seems constant ranging from 19.3% in 2019 to 19.6% in 2045. Nevertheless, the estimated number of elderly with diabetes will show a considerable spike by 2045 (276.2 million) compared to 2019 (135.6 million), which is more than twice that in 2019, if the trend continues. Thus, diabetes prevalence increases with age so the highest estimated prevalence is in adults > 65 years of age.
The past few decades have seen a rise in the number of persons with type 2 diabetes, with more than 60% of these living in Asia (approximately 230 million with an estimated rise above 350 million by 2040) [4]. The South Asian countries will see a 150% rise from 2000 to 2035. According to the Diabetes Atlas 2021, Southeast Asia has 90 million diabetics [5]. Among older adults (≥ 65 years) it is estimated that diabetes will double from 35.5 million in 2019 to more than 78 million in 2045 [5,6]. India and Pakistan are ranked among the top ten countries with elderly persons living with diabetes and would jump from third to second place and tenth to seventh place by 2045 diabetic patients globally [5,7]. India is projected to have 27.5 million elderly persons living with diabetes in 2045 compared to 12.1 million in 2019, and thus, would replace the United States (23.2 million) for the second position globally. Pakistan is estimated to have 6 million compared to 2.6 million for the same years, also scaling up from tenth to the seventh position, globally. Among the SEA countries, India and Pakistan would retain their top two positions in 2030, followed by Bangladesh with more than 2 million elderlies living with diabetes. In Singapore, a local survey found that 29.1% between 60 and 69 years old have diabetes. It also predicted that one in two Singaporeans will experience diabetes by the age of 70 [8]. The prevalence of elderly persons with diabetes in Thailand was 17.2% as per the InterASIA 2003 study [9]. The prevalence of diabetes was ~11%-13% in the Vietnamese population over the age of 60 years [10]. According to the World Diabetes Federation atlas, the number of elderly with diabetes would increase by more than 200% in two decades in the majority of Asian countries. Thus, these data indicate an enormous surge in the aging population with diabetes in the subsequent decades.
The South Asian region is unique as it still faces the dual pandemic of managing undernourishment and infective disorders at one end and has a rapidly increasing burden of non-communicable disorders like diabetes on the other end of the spectrum. This was further compounded by the COVID-19 pandemic [11,12]. Moreover, the unique thin-fat phenotype which is seen in the South Asian region makes the elderly more prone to develop diabetes with a lower body mass index [13,14]. Furthermore, the dietary pattern in the South Asian region, is a carbohydrate predominant non-diabetic friendly eating pattern, which is difficult to change in an older person [15]. This, along with lower per capita income in the elderly and increasing costs of treatment, in a genetically prone ethnicity,  It also impacts the beta-cell physiology culminating in impaired responses to endogenous incretins, thus accelerating the development of clinical diabetes manifestations [18]. makes diabetes in the elderly even more challenging in this region [16,17]. Thus, the rapidly increasing diabetes burden coupled with the unique features of a thin-fat phenotype, high carbohydrate staple diet, poor affordability, and high-risk ethnicity makes the South Asian population a challenging one to manage. This foreseeable health threat prompted the experts across these countries to develop a consensus addressing the unique aspects of diabetes in older adults, particularly

Physiology
Chronological age itself is an independent risk factor for diabetes as well as other chronic diseases [18,19]. Diabetes mellitus is a precipitant of aging. Thus, common pathways partake in the pathophysiology of diabetes and aging. Numerous factors contribute to the pathophysiology of diabetes in older age ( Figure 1).
Regulation of insulin secretion in response to blood glucose levels permits maintenance of normal range. Unlike young adults, older adults become progressively incapable of regulating glucose metabolism. This is especially true in the post-absorptive phase during which normally half of the hepatic glucose is used by the brain and approximately one-seventh by the skeletal muscle [19].
The Baltimore Longitudinal Study of Aging conducted twice in a span of 30 years found that the impaired response to the two-hour OGTT had a positive association with age; though the glucose tolerance deteriorated from the fourth decade up to the ninth decade of life, the alteration from the sixth decade onwards remained significant even after adjusting for BMI, unlike up to the fifth decade. These findings indicate that up to the fifth decade, blood glucose abnormalities are influenced by body fat and physical activity. With advancing age, plasma glucose levels in response to OGTT were progressively higher for every decade of age until they peaked at the seventh decade, more so in males than females. Although the FPG was attenuated after adjusting for BMI, the correlation of 2hG with age remained significant [19].
On the other hand, studies also confirmed that body composition rather than age (across 30-90 years) affects hepatic glucose production [19]. The association between age and insulin resistance is ambiguous. The insulinglucose dose-response curve shifts to the right with age both in single-and multiple-insulin dose studies. These data mean that compared to the young, for the same amount of glucose, twice the amount of insulin is required in the old. This association remained significant after adjusting for BMI [19]. When adjusted for body composition, physical activity, and peripheral insulin sensitivity, the effect of age on the non-insulin mediated peripheral glucose uptake is obscure [19]. Aging may reduce the amplitude and mass of rapid insulin pulses during fasted and fed state; although a reduction in the frequency of ultradian pulses occurs during the fasted state and it is regularized in the fed state in the old, its clinical relevance remains unknown [19].
Studies that evaluated the effect of age on β-cell function using hyperglycemic clamps found that the second phase of insulin responses reaches a plateau in nearly half the duration in the elderly than in the young (120-150 minutes vs. 300 minutes) [19]. Incretins are enteroendocrine hormones (glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) that enhance insulin response from β-cells beyond the amount ascribed to glucose alone [19].
Using a hyperglycemic clamp, in combination with OGTT studies that examined the effect of age on the sensitivity of β-cells to endogenous GIP, researchers found that β-cell sensitivity to GIP is reduced in advancing age. The insulinotropic effect of GIP diminishes with age but is unaffected at very high plasma glucose levels. These suggest that the agerelated impairment in response to GIP is a significant cause of glucose intolerance [19].
Insulin resistance is primarily attributed to visceral obesity. Overconsumption of food leads to accelerated weight gain in older compared to younger persons because aging is associated with gradual loss of muscle mass and gain in fat mass from the fourth decade. Menopause in women and decline in testosterone with age in men aggravates the loss of lean muscle mass and increase in adipose tissue with suppressed catecholamine-induced lipolysis [19].

Alzheimer's disease and diabetes
Alzheimer's disease (AD) and type 2 diabetes mellitus are two of the most widespread diseases in the elderly population globally. Pathologically, AD is characterized by extracellular plaques of amyloid-β and intracellular neurofibrillary tangles of hyperphosphorylated tau [20]. Type 2 diabetes is a metabolic disorder marked by hyperglycemia, insulin resistance, and the formation of human islet amyloid polypeptide that causes pancreatic β-cell dysfunction [20]. The term "type 3 diabetes" may echo the plausibility that Alzheimer's disease denotes a form of diabetes that only comprises the brain. Both tend to have certain common molecular and biochemical features including, but not limited to, insulin deficiency, insulin resistance, impaired energy metabolism, mitochondrial dysfunction, and oxidative stress [21].

Screening and diagnosis
The recent ADA, AACE, and United States Preventive Services Task Force (USPSTF) 2021 recommend widespread screening for prediabetes and diabetes, using FPG, 2h-OGTT, or A1C level, for all adults ≥ 45 years, regardless of risk factors, and screening adults who are overweight or obese (BMI ≥ 25 or ≥ 23 in Asian Americans) with one or more risk factors, regardless of age. If the glycemic indices are normal, repeat screening is recommended at a minimum of three-year intervals. However, the endocrine societies, namely the ESE, the GSA, and TOS differ from the recommendations of the diabetes associations. For patients aged ≥ 65 years without known diabetes, only the measurement of A1c may be erroneous. This is attributed due to potential comorbidities that can affect the lifecycle of red blood cells in elderly persons. Hence, these guidelines recommend that older persons with normal glycemic indices undergo repeat screening every two years; subject to the prospective benefit, terminally ill patients with malignancy or organ system failure, therefore, could be exceptions. In patients ≥ 65 years of age with abnormal FPG or A1c, a 2h-OGTT could be useful in high-risk patients (overweight or obese, first-degree relative with diabetes, Asians, history of hypertension, dyslipidemia, sleep apnea, or physical inactivity). In this high-risk group, shared decision-making is suggested if a patient is frail or finds the investigation procedure excessively onerous [22]. Nevertheless, 2h-OGTT rises by 5-10mg/ dL and FPG 1-2 mg/dl every subsequent decade and may be prone to overdiagnosis.
'The experts in the current consensus agree with the Endocrinology Societies' recommendations in that A1c alone may be inadequate. However, routine screening with FPG alone may also lead to underdiagnosis, hence the ABCDE suggests 2h-OGTT as a better diagnostic marker in the elderly as substantiated by the data from BLSA. ' The BLSA found that if only FPG and A1c are used for diagnosis, more than one-third of those with diabetes mellitus would be missed, particularly Asians with low A1c (because it is influenced by ethnicity) [23]. Therefore, it may be agreed that postprandial hyperglycemia is an important feature of type 2 diabetes in the older population and an OGTT is essential to avoid misdiagnosis based on normal FPG or A1C alone [18]. Hence, the ABCDE recommends OGTT for ruling out diabetes in at least high-risk groups.
'The ABCDE recommends screening at the available timepoints along with other routine investigations in the elderly and routine annual screening in older adults with risk factors, particularly high BMI (overweight/ obese), hypertension, dyslipidemia, and heart disease.' Screening for diabetes not only reduces morbidity but also considerably helps to diminish the risk or severity of associated complications. Among more than 150,000 postmenopausal women, the Women's Health Initiative study found that severity of vasomotor symptoms (night sweats and hot flashes) was proportionally associated with increased risk of diabetes (mild VMS 13%, moderate VMS 29%, severe VMS 48%) irrespective of obesity [24].
'The ABCDE experts believe that menopause transition may be an ideal window for clinicians to screen for diabetes in women. ' In the Asian geriatric population, a meta-analysis revealed that the prevalence of sarcopenia is higher in persons with diabetes than without (15.9% vs. 10.8%); therefore, screening for diabetes is relevant [25].
A study from India reported diabetes as a risk factor for dementia (33.3% of those with diabetes vs. 9% of those without) [26]. Studies from India also have suggested that the ApoE4 allele is significantly associated with AD. Other reports from Asia confirm the association between type 2 diabetes and AD in ApoE4 carriers. A meta-analysis of 28 prospective observational studies found that diabetes increased the risk of all types of dementia by 73% and AD by 56% compared to people without diabetes [27,28]. Therefore, persons diagnosed with dementia should be screened for diabetes.
'The ABCDE experts opine those persons with sarcopenia and dementia should be screened for diabetes.' 1.6 Clinical features 1.6

.1 Unique Symptoms
Elderly persons may present with atypical symptoms, and thus, may delay the recognition of diabetes (Table 2). The subtleness, atypical or delayed manifestation of the classical symptoms are misleading. The elevated renal threshold for glucose excretion and diminished thirst perception alters the presentation of classical symptoms [29][30][31][32].

Traditional Vascular Complications
Older persons with diabetes have poorer end-organ function due to aging and co-morbidities. One or more co morbidities are present in 60% and ≥ 3 co-morbidities are present in 40% of the elderly persons with diabetes [18,33].

Macrovascular (Cardiovascular, Cerebrovascular, Peripheral vascular Disease) Complications
More than 40% of elderly adults with diabetes experience some type of coronary heart disease (CHD) [34]. More than 20% of older adults with diabetes have silent myocardial ischemia [35]. Among patients aged 65-84 years, the prevalence of MI was higher in those with than without diabetes (11.3% vs. 8%; p = .032). The CV health study in adults aged ≥ 65 years showed that the CHD-associated mortality in persons with diabetes either treated with oral agents or insulin was more than twice as high as those without [36]. Thus, among older patients with diabetes, CHD is a leading cause of fatal outcomes. Like CHD, the prevalence of CVD in older adults aged between 65 to 84 years is significantly higher in those with than without diabetes (10.6% vs. 7%; p = .003) [37]. Advancing older age intensifies the risk of developing PVD. This was corroborated by an Indonesian study in which persons with type 2 diabetes in the seventh decade were sevenfold more likely to develop PVD compared to those in the sixth decade of life [38].

Microvascular (Retinopathy, nephropathy, neuropathy) Complications
Unlike the macrovascular, the prevalence of ocular complications of diabetes in the elderly (≥ 65 years) is similar to that in middle-aged (40-64 years) patients (29.5% vs. 28%; p = .64) [39]. Moreover, retinopathy is less common among adults diagnosed with diabetes in older age compared to middle age owing to the lesser duration of disease [39].
Similar to CV complications, long-standing (≥ 25-year) diabetes increases the risk of neuropathy with more than 50% being diagnosed with diabetic peripheral neuropathy (DPN) [42][43][44]. The presence of DPN may impair their balance due to malfunctioning of the three major elements: sensory (lack of motion), motor (impaired movement coordination), and autonomic (the existence of postural hypotension) [45]. Diabetic peripheral neuropathy increases the risk of falls almost five-fold.
Further autonomic neuropathy is suspected to be a modifier of the extent of QT-prolongation which is a known risk factor for ventricular arrhythmias [46]. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial found a higher incidence of hypoglycemia and mortality in intensively treated type 2 diabetes patients. Thus, it is plausible that hypoglycemia induces cardiac arrhythmias in patients with type 2 diabetes, causing the 'dead-in-bed syndrome' [46].

Geriatric syndromes and Diabetes: Geriatricspecific Complications
In addition to the traditional vascular complications which affect the quality of life, the incidence of a set of conditions termed geriatric syndromes, prevails at a greater frequency in older adults with diabetes which leads to diminished self-care abilities and clinical outcomes.

Menopause Prevalence
The proportion of older adults/elderly and those diagnosed with diabetes is progressively increasing, and therefore, menopausal women may form a substantial proportion of the diabetic population (19.4% post-menopausal vs. 12.1% pre-menopausal in Asian women) [47].

Pathophysiology
Menopause has deleterious effects on body weight and adipose tissue distribution. Further reduced energy expenditure along with diminished insulin secretion and decreased insulin sensitivity increase the risk of diabetes in addition to aging. The surge in visceral obesity-associated pro-inflammatory state and androgen excess creates an insulin-resistant environment which increases the incidence of metabolic syndrome compared to reproductive age women (30%-70% vs. 14%-45%). However, data obtained from the Women's Health Study have shown that glucose abnormalities observed during menopause are associated with age and not with the waning ovarian function [48]. On the contrary, several studies have shown that premature menopause, whether spontaneous or induced or lesser number of reproductive years, is associated with a 20%-57% increased risk of diabetes, with some studies reporting a risk of 18% after adjusting for obesity [24,[49][50][51][52]. Diabetes per se may hasten the arrival of menopause [53].

Treatment
The basis of managing menopausal diabetic women is lifestyle intervention involving a diet with an energy deficit of 500-750 kcal/day and ≥ 150 minutes/week of moderate exercise or ≥ 75 minutes/week of vigorous exercise [54,55]. Gradual weight loss (NMT 5%-7% of initial body weight per annum) is recommended; since declining, bone mineral density and sarcopenia are important concerns in postmenopausal women [56,57].
Smoking cessation is recommended because it is a known risk factor for CVD and osteoporosis similar to diabetes and aging [57].
Compensatory estrogen supplementation (hormone replacement therapy-HRT) may improve glucose metabolism regardless of diabetes status. In women with pre-existing diabetes and negligible CVD risk, oral oestrogens may be chosen, whereas, in postmenopausal obese and diabetic women, transdermal 17 β-oestradiol should be preferred. Notwithstanding, a progestogen such as progesterone or transdermal norethisterone should be chosen to prevent effects on glucose metabolism.
In women on HRT, the incidence of diabetes reduced from 21% to 12% owing to the improvement in adiposity-associated changes and pro-inflammatory state. But HRT is not a chronic therapy and evidence substantiating its use for diabetes prevention is weak [58]. However, in diabetic women who attain menopause, HRT enhances glycemic control and thereby lowers the dosages of OHA; however, evidence confirming the effect on CVD is missing. Possibly, HRT may be useful in diabetic women during the early menopausal period unlike in older women in whom destabilization of atheroma may occur resulting in acute thrombotic episodes [57].
Studies also have found a higher incidence of urinary tract infections (UTIs) in postmenopausal women with type 2 diabetes [59]. Use of estrogen, either oral or vaginal, maintenance of healthy vaginal flora using vaginal formulations, and antimicrobial therapy may be useful in the prevention and treatment of UTIs in this patient population [59].

Late-Onset Hypogonadism in Men Prevalence
Late-onset hypogonadism (LOH) or age-associated testosterone deficiency syndrome occurs with advancing age [60]. Hypogonadism is reported in 33%-64% of men with diabetes and men with low testosterone levels are at risk of impaired glucose tolerance [61][62][63]65].

Pathophysiology
The association between LOH and diabetes is bidirectional/two-way; insulin resistance is a shared feature [64]. Insulin resistance is both the horse and cart in hypogonadism [65]. This association may be true because high testosterone levels have shown a 42% reduction in the risk of development of diabetes [65][66][67][68][69]. The concern in patients with diabetes and LOH is that both may additively increase the risk of fractures [64]. Male patients with both conditions have high or normal BMD; however, the bone dimensions are lower, with a significantly decreased bone turnover, which is primarily the predominant effect of diabetes on bone. Thus, reduced osteoblastogenesis and osteoblast activity could be decisive elements affecting bone health in males with LOH and diabetes [65].

Treatment
Although few patients may desire relief from hot flashes, increased sweating, loss of libido, low energy levels, and erectile dysfunction, others may be keen on improving bone health and muscle mass. It is necessary to contemplate those symptoms such as fatiguability, sarcopenia, loss of bone mass, central obesity, and sexual dysfunction that are common to LOH and diabetes. Hence lifestyle intervention is essential along with HRT to enhance its effectiveness. Sometime, nonpharmacological means may even preclude the use of hormone replacement.
Observational studies and systematic reviews have demonstrated the benefits of testosterone replacement therapy (TRT) in hypogonadal men with diabetes. The TIMES2 study showed beneficial effects of TRT on insulin resistance, total and LDL-cholesterol, lipoprotein-a, and sexual health.
Individualized decision-making based on concurred and symptom-led outcomes enhances adherence and improved the probability of attaining endpoints [70].
'Experts recommend, an individualized and patientcentric approach as it is pragmatic and rationale and enhances compliance since the expectation of patients are met [70]. Only TRT may not be adequate, lifestyle intervention may enhance its effectiveness and sometimes even preclude its need'

Prevalence
According to the AWGS criteria, the prevalence of sarcopenia in Asian adults (aged ≥ 65 and > 60 years, respectively) with type 2 diabetes is 15% using the AWGS definition [72,73]. Older adults with sarcopenia may have an increased risk of developing type 2 diabetes as confirmed in large epidemiological studies which showed the double risk of developing diabetes in individuals in the lowest skeletal muscle mass quartile compared to those in the highest quartile [74][75][76]. Lower handgrip strength was also prognostic of higher fasting glucose in subjects over 40 years [77]. The Korean Sarcopenic Obesity Study, Health ABC Study, and the English Longitudinal Study of Ageing demonstrated that patients with type 2 diabetes have three times the risk of low skeletal muscle mass, diminishing muscle mass over five years, and 43% greater odds of low handgrip strength at the end of eight years compared to non-diabetic controls [78][79][80].

Pathophysiology
Sarcopenia similar to LOH is the cause and result of diabetes (bidirectional), predisposing older adults to the development and worsening of diabetes through abnormal glucose clearance due to low muscle mass (normally responsible for 80% glucose disposal), and also increased inflammation due to cytokines produced by the excess adipose tissue [81]. Insulin resistance, inflammation, AGE buildup, augmented oxidative stress, and vascular complications impact muscle health; and weakened muscle health also enhances the risk of developing and worsening type 2 diabetes [82].

Treatment
Exercise and dietary changes, especially improving the dietary protein intake are the cornerstones of therapy for patients with diabetes and sarcopenia [82]. Resistance training is the most effective strategy for improving lean muscle mass, strength, and metabolic health in sarcopenic and diabetic individuals. It also reduces the muscle loss associated with caloric restrictions by 50% [83]. Aerobic exercise improves mitochondria-derived oxidative stress and may at least partially benefit persons with sarcopenia [84]. However, their efficacy in older diabetic and sarcopenic adults is yet uncharted. Furthermore, improving dietary protein is also challenging in the South Asian region.
There are several drug classes in the pipeline which may improve muscle mass, and physical function, thus improving the metabolic status of diabetes patients [73].
'Recommendations: The experts, suggest a balance of dietary modifications, aerobic and anaerobic exercise in older diabetic adults at risk of sarcopenia. In the functional elderly individuals, resistance training should be encouraged.'

Osteoporosis Prevalence
Advancing age and lifestyle, both affect the incidence of type 2 diabetes and osteoporosis and both frequently co-occur. Type 2 diabetes mellitus is a significant risk factor for fractures. Though the Bone mineral density (BMD) may be normal in these persons with type 2 diabetes, the fracture risk is increased, indicating deteriorating bone health.

Pathophysiology
Type 2 diabetes directly affects bone metabolism and strength, certain anti-diabetic medications affect bone metabolism, and there is an association between diabetic complications and risk for falls and subsequent fractures [56]. Long-standing diabetes, its poor control, and associated complications have been shown to increase the risk of fractures [85][86][87][88][89]. Although high FPG is associated with an increased risk of fracture, elevated PPG has shown the reverse which could be due to high BMI [56]. Furthermore, unlike type 1, type 2 diabetes is not a listed secondary cause of osteoporosis in the FRAX online tool which calculates the ten-year fracture risk probability since BMD is usually higher in those with than without diabetes [56]. An increased risk of hip fracture is observed even in persons with higher BMD. Clinical evidence in older adults suggests that femoral neck BMD T-score and the WHO FRAX score were associated with hip and nonvertebral fractures. Compared to those without diabetes, the fracture risk was higher in persons with diabetes for a given T-score, FRAX score, and age [90]. Bone mineral density assessment as a standalone tool may not sufficiently represent bone health in persons with diabetes [91]. Therefore, instead of BMD, the trabecular bone score related to bone microarchitecture and fracture risk which provides information independent of BMD should be preferred in elderly with diabetes and postmenopausal women [91,92].
Hyperglycemia, oxidative stress, and the formation of AGEs, negatively affect bone remodeling. Vitamin D deficiency, which is found in diabetics due to various interrelated factors such as obesity, less physical activity, and reduced sun exposure, aggravates calcium deficiency and may increase the risk of osteoporosis.

Treatment
As per the Indian Society for Bone and Mineral Research (ISBMR) position statement, in elderly individuals with type 2 diabetes, the intervention threshold should be increased to T-score ≤ −2.0 at the femoral neck or total hip or lumbar spine measured by DXA, unlike non-diabetics in whom T-score ≤ -2.5 [93].
Appropriate exercise program after evaluation of the multifactorial fall risk assessment.
Selective use of orthotics could help reduce discomfort, prevent falls and fractures, and improve quality of life. Supplementation with vitamin D3 greater than 1000 to 2000 international units (IU) of daily maintenance therapy is recommended to maintain an optimal serum 25(OH)D level [93]. Adequate dietary intake of calcium with a total intake (including diet plus supplement, if needed) of ≥ 1000 mg/day is recommended. Bisphosphonates, raloxifene, denosumab, and teriparatide increase BMD in patients with diabetes, the former reduce the risk of vertebral and latter non-vertebral fractures [56,[93][94][95].
'The trabecular bone score related to bone microarchitecture and fracture risk should be used for evaluation of osteoporosis in elderly persons and postmenopausal women with diabetes, instead of BMD. In suspected cases of secondary osteoporosis, FPG, PPBG, and A1C should be evaluated in a known or suspected case of Type 2 diabetes.'

Impaired Cognition and Dementia
Aging is an established risk factor for cognitive impairment and dementia, and co-existing diabetes worsens it [96].

Prevalence
A pooled analysis of 14 studies across Asia, Europe, and the USA found that diabetes was significantly correlated with ~ 60% increased risk of dementia, and there was a 40% risk of nonvascular dementia [97]. More than 66,000 elderly (≥ 65 years) patients with diabetes were found to have a 28% greater risk of cognitive impairment compared to those without in a crosssectional study using the Abbreviated Mental Test [98]. The prevalence progressively increased with increasing age; from 13.1% for the age group 65-74 years to 24.1% in those > 75 years [99]. A cross-sectional study from India found nearly 33% of older adults with diabetes at risk of cognitive impairment [100]. The Edinburgh Type 2 Diabetes Study showed that memory worsened progressively with the severity of hypoglycemia and diabetic retinopathy after adjustment for confounders. Similarly, stroke significantly accelerated the cognitive deterioration in a study over fifteen years. After adjusting for this macrovascular complication, the association between accelerated decline in cognition and diabetes was further reinforced compared to nondiabetics [101][102][103].

Pathophysiology
Diabetes may increase the risk of neurodegeneration [96]. Chronic exposure to hyperglycemia can deteriorate cognitive function and other aspects of mental health ( Figure 2). Reports have demonstrated that hyperglycemia is closely related to the development of cognitive impairment and dementia, suggesting that there may be a cause-effect relationship between hyperglycemia and dementia. Depression is a risk factor for the development of age-related cognitive dysfunction in people with diabetes, independent of vascular complications [104]. should be prioritized for a screening of cognitive impairment at the primary care level [100]. Annual screening for cognitive functions using simple appropriate tools (Mini-Mental State Examination Mini-Cog, and the Montreal Cognitive Assessment) should be conducted [105][106][107][108][109][110]. It is important to note that although robust data are missing currently, recognizing cognitive decline early will have a significant effect on diabetes management in these older adults. The cognitive assessment also should be conducted when glycemic control is impaired. Frequent episodes of hypoglycemia also should prompt cognitive assessment, because it could be due to the inability to identify hypoglycemic signals and consequently incapability of preventing it. Elderly with diabetes who are found to be positive on screening should be referred for prescribed cognitive/neuropsychological assessment.

Treatment
A cross-sectional analysis of the large PREDIMED-Plus study on the elderly suggested that once diabetes has been diagnosed, cognitive decline prevention strategies need to be implemented to improve treatment adherence and quality of life [111]. When cognitive decline is diagnosed, appropriate behavioural therapy should be initiated [112]. No disease-modifying therapy is currently available to cease or decelerate the processes that lead to dementia [113]. Only symptomatic (psychotropic) and standard (cholinesterase inhibitors (ChEIs) and a partial N -methyl-D-aspartate antagonist) AD therapies are currently available [114].

Hypoglycemia Definition
Consistent with a Consensus Report from the ADA, AACE, and other Diabetes Associations three levels of hypoglycemia have been defined-level 1 or hypoglycemia alert (≤ 70 mg/dL); level 2 or clinically significant hypoglycemia (< 54 mg/dL) and level 3 or severe hypoglycemia, associated with severe cognitive impairment necessitating hospitalization for recovery (no specific glucose level).

Prevalence
There has been a steady rise in the occurrence of hypoglycemic episodes due to the increasing trends in achieving tighter glycemic control and prevalent co-morbidities. Hypoglycemia is the second most common adverse drug reaction. Insulin was the second most common medication associated with ED visits in older people ≥ 65 years, due to hypoglycemia [115,116]. The exact incidence of hypoglycemia is not known but it is higher in older than younger persons with diabetes. A one-year, prospective, observational study found significantly higher episodes in persons aged > 70 years than < 60 years old (12.8% vs. 9.0%, p < .01) and more persons in this group needed medical assistance (0.7% vs. 0.1%) [117]. The incidence is even higher in the community setting up to 41.9% over one year [118].

Causes
The counter-regulatory responses to hypoglycemia in persons with diabetes are defective [119]. The risk of hypoglycemia is increased in older adults due to several co-morbidities, including diminished hormonal regulation and counter-regulation, insufficient intake of water and/or food, decreased intestinal absorption, and cognitive impairment [120]. Polypharmacy, frequent in the elderly may increase the risk of severe hypoglycemia [121]. This patient population also demonstrates age-related changes (increased fat: muscle mass ratio, decreased renal function, decreased drug clearance) in pharmacokinetics and pharmacodynamics thus potentially increasing the risk of adverse events [121,122].

Presentation
In older adults, the counter-regulatory response depends on the frequency of hypoglycemic episodes they experience, with recurrent episodes reducing the glycemic level at which these mechanisms are activated [115]. Thus, the elderly with diabetes not only manifest fewer pronounced symptoms but also do so at progressively lower glucose levels compared to their younger counterparts. They tend to present with neuroglycopenic symptoms (i.e., dizziness, visual disturbances, increased agitation, and/or confusion) rather than classical adrenergic symptoms (i.e., palpitations, sweating, tremors), leading to loss of self-correction window [123]. Also, lack of cerebral glucose causes non-specific symptoms like nausea, falls, and unsteadiness. The neuroglycopenic symptoms are also non-specific because these may occur due to several other conditions, especially in the elderly [122,123]. Furthermore, such symptoms may occur even below the level associated with neuroglycopenia, a condition termed hypoglycemia unawareness. Thus, in older adults, hypoglycemiaassociated autonomic failure can occur [115]. Therefore, due to the non-specific nature, multiple potential causes, and co-morbidities, recognizing hypoglycemia in the elderly is challenging.

Management
Periodic feedback to determine awareness of hypoglycemia, any associated symptoms, adherence to treatment, meal frequency, and unintentional repeat doses should be obtained from patients and their caregivers, (e.g., selected questions from the Diabetes Care Profile) [124,125 ]. Also, any future risk should be evaluated using validated risk calculators, and these older patients should be categorized based on the severity of anticipated hypoglycemia [126].
Consideration should be given to cognitive abilities and co-morbidities in older adults when determining the treatment strategy. The most obvious method is to select anti-diabetic regimens with a lower risk of hypoglycemia. Glycemic targets should be adjusted to avoid any risk of hypoglycemia, and at the same time, not enhance hyperglycemia [147].

Severe Hyperglycemia
Hyperglycemic hyperosmolar syndrome (HHS) is a particularly severe complication of unidentified or sub-optimally treated hyperglycemia in older adults. Dehydration, electrolyte abnormalities, urinary incontinence, dizziness, and falls should prompt appropriate glucovigilance to avoid HHS because it has a poorer prognosis in older than younger adults [127][128][129]. Providing a detailed approach to its management is beyond the scope of the current document.

Prevalence
In the data derived from the NHANES I populationbased sample aged 55-74 years, diabetes was associated with an almost double risk of having a serum albumin concentration < 38 g/L. Also, reduced albumin is associated with an unfavourable metabolic profile [131].

Causes
Various studies demonstrate a progressive reduction of albumin serum concentration between 0.08 and 0.17 g/L/year, associated with aging [132]. Diabetes may be associated with impaired liver production of albumin because insulin is an important regulator of its synthesis [133]. Cross-sectional studies show that hypoalbuminemia is an independent risk factor for frailty in elderly with diabetes, suggesting relative malnutrition in these frail patients [133].

Presentation
Modest to very low serum albumin concentrations are associated with muscle wasting, disability, and higher morbidity and all-cause mortality in older persons [134]. Because albumin functions as a low-affinity, high-capacity carrier of several different endogenous and exogenous compounds acting as a depot and a carrier for these compounds, a drop in its serum levels may lead to increased free drug concentration in the plasma, more rapid hepatic metabolism, or both, which needs to be taken into consideration when treating diabetes and co-morbid diseases [135].

Management
Studies suggest serum albumin concentration of elderly people to be maintained at ≥ 4.0 g/dL to prevent frailty [136]. Such elderly with diabetes should be supported with sufficient high biological value protein and energy intake for anabolism.

Dyselectrolytemia Prevalence
Among the various electrolyte abnormalities commonly found in the elderly, hypernatremia and hyponatremia (11%-18%) are the most frequent [137]. Both are associated with a high fatality rate. Based on the settings and the definition, hyponatremia ranges from 2.5% to as high as 50%. Electrolyte disturbances are frequent in persons with diabetes, particularly the elderly.

Causes
Dyselectrolytemia may occur due to altered dispersal of electrolytes corresponding to hyperglycemia-induced osmotic fluid shifts or total-body deficits owing to osmotic diuresis [138]. Elderly persons are at particular risk due to a decline in cognitive ability and may experience a syndrome of inappropriate antidiuretic hormone (SIADH) secretion [138]. Pharmacotherapies used for the treatment of diabetes also may result in electrolyte disturbances, specifically dysnatremia. Additionally, higher water intake in combination with a low salt diet adopted by many elderly patients and hypoproteinaemia due to diabetes and malnutrition may increase the risk of 'Tea and toast' hyponatremia [139].

Caution/Careful considerations
Because advancing age and diabetes (irrespective of hyperglycemia) per se increase the risk of dysnatremia, careful consideration of therapies that affect the electrolyte balance is necessary [140]. It is noteworthy that unlike TZDs and first-generation SU, secondgeneration SU rarely causes dysnatremia. SGLT-2i and GLP-1 agonists have not been found to cause electrolyte abnormalities [139,140]. Thiazide diuretics, and to a lesser, extent loop diuretics, induce hyponatremia [139]. Antidepressants associated with hyponatremia are predominantly attributed to SSRIs, SNRIs, and mirtazapine in persons ≥ 60 years of age [139]. Elderly persons treated with anti-epileptic drugs (AEDs) such as valproic acid, phenytoin, or topiramate have a higher risk of being hospitalized with hyponatremia. Other AEDs such as carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, levetiracetam and gabapentin also induce hyponatremia [139].

Malnutrition Prevalence
It has been suggested that the prevalence of malnutrition or its risk in elderly patients with diabetes is greater than 50% [141]. According to the Mini Nutritional Assessment (MNA), malnutrition is higher in the elderly with diabetes than in those without diabetes [141].

Effects on medication
Malnutrition is associated with functional impairment (decreases in activities of daily life, grip strength, physical performance of the lower limbs) and consequently poor quality of life, longer hospital stays, and increased rates of institution and mortality [141]. Malnutrition also plays a key role in developing frailty and sarcopenia. Muscle hypertrophy and atrophy may occur due to poor protein intake [141]. It can hinder normal brain function and encourage cognitive loss [141]. Thus, in elderly patients' diabetes and its complications are compounded by malnutrition [142].
Besides the disease prolonged use of metformin causes vitamin B 12 deficiency in 10%-30% of patients with diabetes. It may worsen cognitive performance in elderly patients [143]. However, vitamin B12 deficiency also has been reported in diabetic patients not taking metformin [144,145]. These factors should be specially considered in patients who develop paresthesia and neuropathy [146].

Goals for glycemic control in elderly
Considering the multiple co-morbidities and syndromic factors associated with advancing age, the usual glycemic targets recommended in younger adults are not justified in older adults with diabetes. In older adults with diabetes, the aim is to maintain an optimal quality of life, which in turn, depends on individual patient risk factors concurrently avoiding acute glycemic extremes.
Hypoglycemic events are a frequent occurrence in older adults due to diminished sympathetic counterregulatory responses. Moreover, hypoglycemia predisposes this patient population to increased risk of diminished cognition, dementia, all-cause hospitalization, and all-cause mortality [147][148][149]. Hyperglycemia due to undertreatment increases the risk of dehydration, dizziness, falls, and long-term mortality [18,150].
Inadequacy of quality RCTs focussing on older diabetic adults impedes the establishment of suitable glycemic goals. Pivotal trials namely ACCORD, VADT, and ADVANCE trials in older adults have failed to demonstrate any additional benefit in cardiovascular outcomes with tight glycemic control as per AACE (A1c < 6% or < 6.5%), rather ACCORD was prematurely No specific target but minimizing symptoms related to hyperglycemia discontinued due to higher mortality (p = .04) and higher frequency of hypoglycemic events (p < .001) in the intensively treated group [151][152][153]. However, even an A1c level > 8% is associated with increased morbidity and mortality [154]. Based on this clinical evidence in older diabetic adults, rather than focussing on contentious glycemic targets, attuning/ personalizing the glycemic goals as a function of the patient's duration of diabetes, life expectancy, functional status, concomitant disease conditions should be considered. Management should aim at a realistic and modest glycemic goal of A1c between 7% and 8% rather than tight control in old diabetic patients (Table 3) [155]. It is worth noting that although there are small differences in the A1c targets among guidelines, all of them recommend a personalized/individualized approach to diabetes management (Table 4). 'The ABCDE experts agree that there is no 'single best' -the best varies for each patient, therefore instead of arguing on the glycemic goals, a tailored approach would be vital in maintaining an asymptomatic and quality life for the older adult with diabetes.'

Prevention of falls
A major cause of morbidity and mortality in older adults with diabetes is falling; the risk in the elderly with diabetes is 17-fold higher compared to those without diabetes [156]. The three-year Longitudinal Ageing Study in Amsterdam found a 67% greater risk of recurrent falls (≥ 2 falls/6 months) in the elderly (> 65 years) with diabetes compared to those without which persisted after adjusting for other risk factors [157]. Overall, 18% of the cohort from the Study of Osteoporotic Fractures followed for more than seven years experienced recurrent falls. Compared to nondiabetics, diabetics treated with OHAs and insulin are at 68% and 178% higher risk of recurrent falls (> 1/year) [158]. These findings for insulin were substantiated again by the five-year Kaiser Permanente Registry in the elderly (> 60 years) [159]. Diabetes is also known to increase the risk of psoriatic, gout, and rheumatoid arthritis, causing movement-limiting pain and mobility weakness. Persons with diabetes are also at twice the risk for osteoarthritis compared to the general population.
It is essential to screen and modify the risk factors for falls in elderly persons with diabetes and formulate interventions tailored to address the detected issue (balance, walking dysfunction, reactions, muscle weakness, pain) (Table 5) [156,160,161].

Lifestyle management
In the elderly with diabetes, lifestyle management should be tailor-made to their frailty status. Optimal nutrition with sufficient protein intake along with a structured exercise program is aimed at decreasing sedentary intervals and increasing mobility in frail elderly persons with diabetes. In the elderly who are not frail, but are overweight or obese, given its multiple benefits, an intervention aimed at weight loss is recommended [162].

Diet and Nutrition
Nutritional status should be assessed for older patients with diabetes for the preclusion of cognitive impairment, frailty, and mortality is BMI ≥ 30 kg/ m 2 , weight gain (> 10%), metabolic syndrome (< 75 years of age), sarcopenic obesity, BMI < 18.5 kg/m 2 , inadvertent weight loss, and malnutrition. A dietitian's referral should be advised in this regard because they provide advice for maintaining nutritional status and medical nutrition therapy, when necessary, bearing in mind the patient's personal preferences (age-related deterioration in taste, dental problems, co-morbidities, dietary restrictions, poor gastrointestinal function), food availability, and individual goals which improve QoL [162,163] (Table 6).

Exercise and Physical activity
Frailty prevalence is ~10% in the population over 60 years old and increases to > 25% in those ages ≥ 80 years of age [164]. A cross-sectional study showed that compared to Europeans, South Asians (~50 years of age) need to undertake ~230 minutes of moderateintensity physical activity every week [165].
In older adults, apart from improved glycemic benefit, exercise also improves body composition and arthritic pain, reduces falls and depression, increases strength and balance, enhances the quality of life, and improves survival [166][167][168]. It is prudent to get the patient to start an exercise or physical activity program gradually and encourage them to remain consistent, with recommended activities based on functional status (Table 7) [169][170][171].

Stress Management
Chronic diseases like diabetes and associated socioeconomic factors can be major causes of stress among

Protein intake
Attenuates the decline in muscle mass and insulin sensitivity that occurs with increasing age and diabetes.
Helps in an increase in protein anabolism, 'high-quality' weight loss (fat loss and muscle preservation/gain), enhanced glycemic control, daily appetite control, and satiety.
Protein intake should be 1.0-1.2 g/kg/day in older adults and 1.2-1.5 g/kg/day in those who are at risk of malnutrition.

Dair y foods
Increased consumption may be beneficial for older adults with diabetes due to the combined effect of dairy on both insulin sensitivity and lean body mass.

Diet rich in fruits and vegetables as well as exogenous antioxidant vitamins (such as vitamins E and C and Carotenoids) and minerals
Restores the skeletal muscle redox homeostasis and prevents oxidative stress, thereby contributing to muscle maintenance. To reduce the risk of coronary heart disease and cerebrovascular disease the elderly. Chronic psychological stress may increase inflammatory and platelet aggregation responses and result in poor diabetes control due to activation of the hypothalamic-pituitary-adrenal axis [172]. If such stressors are not managed, the elderly are at risk of developing mental health issues like anxiety and depression. Considering that psychosocial impact affects morbidity and mortality in persons with diabetes, psychosocial facets should be included at all levels of diabetes management. Thus, elderly persons with diabetes require access to stress management along with treatment of metabolic abnormalities to improve treatment adherence to achieve good glycemic control, reduce the risk of complications and improve QoL [173]. Psychosocial stress management could include Cognitive behavioral therapy, motivational therapy, problem-solving therapy, coping skills training, and family behavior therapy (Table 8) [174][175][176][177][178]180,189].

Sleep Hygiene
Diabetes can cause direct sleep disturbances due to nocturia, polyuria, diabetic neuropathy and neuropathy pain, and other several chronic illnesses that can impair sleep and quality of life [181]. It is important to address their sleep issues and the impaired quality of life due to inadequate and fragmented sleep, as it may be severely affecting their glycemic control and quality of life. Therefore, sleep education is an essential aspect of diabetes management in the elderly (Table 9) [182][183][184].

Problem-solving strategies
• It is important to identify patients' exaggerated fears or worries as well as extreme callousness regarding disease and treatment. These issues should be addressed using problem-solving strategies.

Motivational interviewing
• Motivational interviewing self-management program leads to significant improvement was found for self-efficacy, self-care behaviour, glycemic control, and quality of life (daily life satisfaction, influence of disease) • Assessment of perception of self-management level, hurdles, and coping strategies for self-management and goal setting should be performed.
• Use of verbal persuasion and appreciation for sustaining self-care. Reassess barriers and offer more coping strategies if goals are not met.

Family behaviour therapy
• Involving family members and caregivers in interventions for the elderly population may be vital for providing them with social support related to their diabetes management.
• Spouse participation in diabetes education program for elderly diabetic patients showed greater improvements in knowledge, metabolic control, and stress level than those who participated alone.
• Such programs involving family social support training have also helped older patients to maintain dietary restrictions.

Social Interaction
• Communication between social groups for the elderly at sports centres, local parks, religious centres may improve selfmanagement skills and the elderly may also find motivation from patients of the same age-group Table 9. NPI for elderly persons with diabetes: methods to improve sleep hygiene [182][183][184] • The patient should be educated to maintain a pre-sleep routine, the same sleeping and waking hours (7-8 hours) • Advice getting sufficient sunlight during the day • Suggest using a fan or white noise machine to block disturbances • Advice sleep in a quiet dark room and use of comfortable bed and clothes • If unable to fall asleep, suggest reading, listening to soothing music, and trying to sleep again • Advice avoiding day-time napping • Advice avoiding CNS stimulating substances (caffeine, alcohol, tobacco) and activities (screens-television, mobiles, computers) 90 minutes before bedtime • Advice avoiding spicy, heavy dinners

Environmental Modulation
Aging with individuality is vital for the elderly which includes living independently in one's home and choosing on spending one's time [185,186]. These aspects are influenced by an interaction between health and the environment. Physical environmental barriers can generate hazards in the home and community. Elderly individuals with chronic conditions and www.diabeticstudies.org Rev Diabet Stud (2022) 18:100-134 functional limitations are not only at significant risk for adverse health events (such as falls) and injuries but also face difficulties in performing ADLs. Moreover, these barriers attenuate the effectiveness of caregivers, assistive technologies, and health care devices sometimes necessitating early institutionalization (Table 10) [187,188]. 'Experts suggest that given the less consultation time (~3.5 minutes) and large patient pool, physicians should recruit dietitians and patient care educators for patient benefit since lifestyle changes form the cornerstone of diabetes management.'

Pharmacological
The pharmacotherapy for the elderly should be directed at achieving good glucose control, without causing hypoglycemia, and preventing symptomatic hyperglycemia. Intensive glycemic control should be avoided and so should polypharmacy. Polypharmacy increases the risk of drug-drug and drug-disease interactions, particularly in elderly persons with diabetes with sensory and cognitive deficits due to age [189]. Such deficits may impede the prompt conveying of initial symptoms of adverse drug events. Therefore, pharmacotherapy for the elderly person with diabetes should be chosen based on individuals' functional capabilities. These include but are not limited to visual, motor, or cognitive abilities, pre-existing comorbidities, and risk factors (Table 11 and Table 12).

Dose adjustment Strengths/Advantages
Biguanide Metformin [190][191][192] • • Lower risk of hypoglycemia • Self-monitoring of blood glucose is not needed to adjust the dose • Weight loss • No differences in the efficacy and safety profile between elderly and younger patients • Non-inferior to placebo in reducing MACE in patients with established CVD and potentially for those at high risk for CVD [198,199] [196] Glycaemic control was equivalent with glibenclamide and gliclazide but the incidence of hypoglycaemic (symptomatic, serious) reactions was significantly greater (twice) with glibenclamide [200][201][202][203] Glibenclamide contraindicated Risk factors for severe hypoglycaemia [202] recent hospital admission advanced age (>80 years) -Extensive use of comedication Decreasing endogenous (β-cell function may limit the therapeutic efficacy of sulfonylureas [204] No Use of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients ≥65 years. Higher risk of readmission for heart failure with TZD treatment and lower risk with metformin treatment Not be used in patients with heart failure NYHA class III or IV. Treatment decisions must remain individualized, with clinicians weighing the potential benefits and harms of TZD treatment, especially among high-risk elderly populations No Lee (2011/3,752 ambulatory men aged ≥ 65 years) [206] Lose less lean muscle mass Beneficial for older adults, frail elderly patients, but the downside is increased risk of fractures, probable macular edema, heart failure, and fluid retention Ye (2016/544,093 participants, age not stated) [197] The incidence rate of dementia was reduced with thiazolidinediones, with a marginal trend toward significance

Might protect against incident dementia Yes
Schwartz (2006/69/70-79 years) [207] BMD loss only in women, proportional to the duration of use Use for continuously 5 years, average BMD loss 3% more than expected.
Patients with diabetes already have an increased risk of fracture. TZDs associated with bone loss and increased risk of bone fractures, in elderly women [208,209]. Not recommended for use in older adults with preexisting osteoporosis, if prescribed BMD needs to be closely monitored Solomon (2009/20,964 Medicare beneficiaries, ≥ 65 years) [210] TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin. Vildagliptin was shown to be effective, safe, and well-tolerated in a wide sample of older patients, which was characterized by an elevated prevalence of mild renal insufficiency, multiple comorbidities, and polypharmacy Vildagliptin has similar efficacy to TZDs as an add-on to metformin over 3 months regardless of race, age, or BMI Yes Schweizer (2011/301/77 years) [215] Pooled analysis showed that in the very old patient population with comorbidities and polypharmacy, vildagliptin led to a clinically relevant A1C reduction either as monotherapy or add-on Has a similar safety profile in younger and older patients.
Modest decreases in LDL-C, triglycerides, and total cholesterol Significantly reduce SBP and DBP Multiple pleiotropic effects that can help reduce polypharmacy in older diabetes patients with co-occurring chronic diseases (e.g. fatty liver disease and hypertension) and syndromes (such as sleep apnea and Parkinson's disease).
Improved hepatic function in NAFLD as measured by transaminase levels, biopsy, and images Prevented the expected decline of cerebral metabolic rate for glucose uptake in the parietal-temporal frontal and posterior cingulate cortices.
Neuroprotective, and even regenerative, properties may be utilized in patients with AD or PD Cochrane review 2017 [224].
No relationship between the use of diabetes medications and cognitive decline during a follow-up period of 40-60 months

Therapeutic parsimony
Geriatric physiology and psychology are different from those of younger and healthy adults [234]. Due to age-related changes in pharmacokinetics and pharmacodynamics, elderly persons respond to lower doses of several drugs [235]. Furthermore, they also occasionally forget to take their medicines at the right dose and at the right time. Unfortunately, however, polypharmacy becomes more common with advancing age. This is attributed, at least in part, to the presence of multiple co-morbidities and complications in this population.
The law of therapeutic parsimony provides us with a framework in which to plan therapy for geriatric persons living with diabetes. It states the following: 'minimal therapeutic interventions should be used, in place of multiple ones, as long as this can achieve equivalent therapeutic outcomes' [236]. Being cognizant of this law, an attempt should be made to minimize the number of tablets/capsules or pill burden, and the frequency of their administration. A few means of achieving this end include prescribing rational fixeddose combinations, which in turn, reduce the dose of individual agents. Agents with proven pleiotropic effects also could be preferred, provided adequate efficacy is assured. It should be suggested to the patient that all medications can be taken at the same time, perhaps five minutes before a meal or immediately after a meal. It also should be ensured that while prescribing brand names, strips or tablets that are similar in appearance are not prescribed. It is common for the patient to get confused between two strengths of the same medication; e.g., 1 mg and 2 mg of glimepiride tablets due to similarity in packaging.

Glycemic Monitoring
Optimal glycemic control in elderly persons with diabetes can be achieved through certain lifestyle adaptations, adjustment, and individualization of the therapy, which invariably depends on careful selfmonitoring and control. Blood glucose monitoring can be done by different methods (Table 13).
A1C Recommendation: It should be performed twice annually for stable glycemic control and four times for unstable/need change in treatment [240].
Self-monitoring of blood glucose (SMBG): International guidelines recommend ≥ three times daily pre-prandial capillary blood glucose measurements for patients with intensive insulin therapy or insulin pump carriers; in other cases, the frequency of SMBG should be individualized depending on the treatment scheme and glycemic level control. Postprandial monitoring is recommended for cardiovascular prevention. Continuous glucose monitoring-time in range (CGM-TIR): For older patients including high-risk ones (those with complications or co-morbidities, such as cardiovascular or kidney disease, cognitive deficits, osteoporosis, fractures, or joint disease), the TIR target is > 50% [241]. For the elderly TIR, the target was lowered from > 70% to > 50% and reduced TBR to < 1% at < 70 mg/dL (< 3.9 mmol/L) to place greater importance on reducing hypoglycemia than maintaining target glucose levels [242].

Methods to improve adherence and reduce dosing errors
Advances in technology are being used to improve elderly care and quality of life aiming at both diseasespecific and elderly-specific parameters. Table 14 and

Table 15
The application of technological advances in elderly care may be broadly categorized.
Elderly persons have different barriers to adherence, the most common ones being remembering to inject themselves or injecting the correct dose or maintaining supplies. Therefore, in this patient population with diabetes, insulin pumps and continuous delivery devices certainly can facilitate improving adherence, and consequently, glycemic control [245]. Moreover, the use of an insulin delivery system is more accurate and precise than insulin administration via injections [249]. Use of insulin delivery systems also helps to reduce hypoglycemia and consequently its complications. (Table 16) Self-monitoring of blood glucose (SMBG) is a key component of diabetes management; however, it is limited by its staticity. Unlike SMBG, Continuous glucose monitoring (CGM) provides a trend of glycemic status, and therefore, is used for pattern management and assessment of glucose excursions. Hybrid systems combine insulin delivery and monitoring systems, enhancing the convenience of use [246,249]. The patients or the caregiver must be educated on interpreting and utilizing the information obtained from monitoring devices so that it affects adherence positively.
Self-monitoring is a basis of behavioral lifestyle interventions. The incorporation of personal fitness technologies into behavioral interventions enhances physical activity, decreases sedentary behaviours, and improves glycemic control in older adults. Activity trackers may boost physical activity through the amalgamation of analytically-tested behavioral change techniques such as goal-setting, self-monitoring, social support, social comparison, feedback, and rewards.
Studies have observed weight loss, social connection, and increased activity awareness in the elderly using activity trackers (Table 17 and Table 18) [247,248].

Religious/Cultural Fasting
Many patients with diabetes may fast for religious or cultural reasons. Elderly persons often are more religious and may insist on fasting. Fasting could be either regular or intermittent for a few days in a week or continuously for an entire month. Management of intermittent fasting is more challenging because the pharmacotherapy schedule becomes more complex compared to when it is continuous. Maintaining euglycemic status is even more complex in patients using insulin therapy. The rate of complications is significantly greater in older adults than in younger ones with diabetes. Therefore, management is even more challenging for the elderly. Besides, this population is excluded in most trials, and guidance is based on expert opinions rather than clinical evidence.
The experts suggest the management of diabetes should be attuned to the patient's lifestyle, not the opposite as a reassurance of living a normal life even with diabetes. For the elderly who wish to fast, a careful risk-benefit analysis must be performed. The results should be discussed with the person and his/her family to arrive at a shared decision.
The other aspect of fasting is dehydration in case liquids are also restricted or the patient is on diuretics or SGLT-2i or those with brittle diabetes or renally impaired. Most liquid intake depends on the type of food consumed, particularly in the elderly who depend on a liquid diet (juices and soups). These patients also should avoid fasting or can observe fasting provided extreme caution is followed along with recommended dietary and medication modifications. If the patient still insists on fasting, the use of SGLT2i must be avoided.

Sick Day Rule
Most common illnesses in the general population can assume serious complications in people with diabetes, particularly in the elderly who have a compromised immune system. Certain illnesses like common cold or flu, upper and lower respiratory infections, urinary tract infections gastrointestinal tract infections, and skin infections are accompanied by high body temperature. These illnesses can dysregulate the plasma glucose resulting in serious complications like DKA or HHS.
Our experts agree with the ADA and IDF-Europe recommendations for the management of sick patients with diabetes. The anti-diabetic medication should be continued; in particular, insulin should not be discontinued but plasma glucose should be more frequently monitored (at least every four hours). Adequate hydration and oral caloric intake should be • Uses technology to stop insulin delivery for up to 30 minutes to 2 hours if the glucose level reaches a preset low limit and the user doesn't react to a low-glucose alarm • Bolus prandial insulin needs to be initiated • Reduce hypoglycemia • Reduce glucose variability • Improve glucose control • Downloadable reports • Alarm/alert Table 17. Technologies important for elderly persons with diabetes for Non-specific parameters [244] Information and Communication Technologies (ICTs) • Monitoring of vital signs • Provision of information through calls or educational contents Monitors the evolution of gait speed, muscle power, and involuntary weight loss to define preventive strategies to avoid disability.
Home-based technology mHealth technology (Apps in smartphones) • May enable continuous and transparent monitoring of the independent elder Identifies older people at risk of disability Activity trackerssensor-based wearable devices (smart watched, bands) • Automatically track and monitor various indicators of physical activity -steps taken, stairs climbed, duration and quality of sleep, pulse or heart rate, calories consumed or burned, and even mood, moderate-intensity aerobic and muscle-strengthening activitieswalking, jogging, bicycle riding, yard work, and gardening -Synchronize obtained data with users' personal accounts, for easy access from any device.
• Convenient tool for this age group since it provides unbiased feedback about physical activity amount and intensity • Delivers prompts via short message service • Increases physical activity   [250,251]. Glucose lowering therapy should be adjusted according to oral caloric intake. Fatigue, weight loss, and polyuria are indicators of hyperglycemia. Plasma glucose above 270 mg/dL, ketones in the urine, and excessive thirst are signs of DKA. Vomiting, abdominal pain, tachycardia, and reduced level of consciousness constitute medical emergencies.

Inpatient management
In critically ill patients in the ICU as well as for most patients admitted for general illnesses or surgery in the www.diabeticstudies.org Rev Diabet Stud (2022) 18:100-134 non-ICU setting, the various guidelines recommend target glucose between 140-180 mg/dl (Table 19). Insulin, preferably delivered intravenously, remains the best alternative for maintaining glycemic status in the inpatient setting, specifically in the ICU. However, evolving data suggest that OHAs from the DPP-4i class either as monotherapy or in combination with basal insulin may be used in patients with mild to moderate hyperglycemia. In a non-ICU setting (general medicine or surgery) the recommended total daily insulin dose for most people should start between 0.15-0.3 units/kg body weight, with lower doses of 0.1-0.15 units/kg recommended for older patients with renal failure (eGFR < 60 mL/min/1.73 m 2 ), history of hypoglycemia, or poor oral intake [252]. In addition, patients with enteral or parenteral nutrition should be monitored for glucose at 4-6-hour intervals to avoid hypo-hyperglycaemia [171].

Summary
The panel opined that the current and expected geriatric population with type 2 diabetes in Asia is enormous along with a huge spectrum of dietary and disease (communicable and non-communicable) disparities unique to the region. Hence, management of diabetes in the Asian geriatric population is indeed challenging. The Best Practice Document has considered the conventional as well as unique factors when proposing recommendations for glycemic targets. Particular attention has been paid to the geriatric syndrome and management of type 2 diabetes with pharmacological and non-pharmacological interventions aligned to its existence. The use of technological aids to monitor the disease status and avoid several risks specifically in this vulnerable population has been emphasized. Modifications to diabetes management in special situations like religious fasting or hospitalization or days when they feel unwell have been addressed. The panel has been thorough in addressing aspects specific to geriatric diabetes.