ADA and AGSa
Mrs. O. (Case 2)
67-year-old Hispanic patient
Medical recently diagnosed T2D.
Functional preserved functional status
Mental: mild cognitive impairment (MCI) .
Social: lives at home, independent, has family support
Or 6.5–7.5 %
As long as no hypoglycemic events
There is potential harm in lowering HbA1c <6.5 % in older adults . Implement lifestyle changes towards modest intentional weight loss. Start low, go slow, with pharmacologic interventions, and monitor; follow up and titrate to reach the target
Two years later, Mrs. O. presents with one or several of the following scenarios:
Medical (1): a myocardial infarction, and heart failure
Medical (2): Parkinson’s disease, chronic kidney disease stage 3, and emphysema.
Medical (3): newly diagnosed colon cancer.
Functional: requires assistance with ADLs (bathing and dressing)
Mental: MCI has progressed to dementia
Social: lives in an Assisted Living Facility which cannot administer insulin four times per day
Or 7.0–8.0 %
As long as no hypoglycemic events
Studies support avoiding intensive glycemic control in individuals with macrovascular complications.
Similar approach applies in multimorbidity (more than three chronic diseases), cancer, or mild to moderate cognitive impairment, and with two or more Instrumental ADL impairments
Six years later, Mrs. O. presents with one or several of the following scenarios:
Medical (1): has a massive stroke with major neurological and functional sequel
Medical (2): develops severe liver damage due to acetaminophen toxicity, and now presents end-stage liver disease
Medical (3): develops rapidly progressive chronic kidney disease, and requires hemodialysis
Functional: loss of physical function, bedridden, dependent for most activities of daily living
Mental: advanced dementia
Social: admitted to a nursing home
Her family requests a focus on quality of life and avoidance of polypharmacy
Or 8.0–8.5 %
And up to 9 % in cases unlikely to benefit from lower values, due to limited life expectancy
Higher targets relate to lack of benefit from more aggressive interventions and the need to avoid hypoglycemia.
Still aims to avoid severe hyperglycemia and glycosuria, which may be associated with impaired wound healing, infection, and urinary incontinence, volume depletion, hypernatremia, delirium, falls, as well as hyperosmolar hyperglycemic nonketotic syndrome or diabetic ketoacidosis
22.5.2 Diabetes and Renal Disease
Progressive loss of renal function is associated with aging although the degree of loss is highly variable. Chronic kidney disease (CKD) is a complication of diabetes or can be associated with hypertension (HTN), another common age-related disease. In addition, older adults may be treated with pharmacologic agents that could lead to kidney damage. Since several anti-hyperglycemic medications (Table 22.2) are renally excreted, the management of older adults with diabetes and kidney disease is challenging, particularly in those with advanced CKD.
Pharmacotherapy for diabetes in the older adult
HbA1c Target based on clinical scenarios In Table 22.1
Second line (a)
Or 6.5–7.5 %
As long as no hypoglycemic events
Maximize lifestyle interventions. Avoid medications associated with weight gain
• May help with weight loss
• Start 500 mg PO with largest meal, monitor tolerance, increase slowly, towards target of 1000 mg PO BID
• Monitor renal function, counsel patients when to hold medication in settings where renal function may be impaired (procedures using iodinated contrast)
Glucagon like peptide-1 receptor agonists (GLP-1 RA)
• Reduces appetite, useful if the patient has concomitant obesity
• Requires injection (check manual dexterity, vision)
Dipeptidyl peptidase inhibitors (DPP)-4 inhibitors
• Weight neutral
• May be preferred if the patient has limitations in vision, or prefers an oral agent
• Dose adjust based on renal function; except linagliptin
• Risk of urinary tract infections and ketoacidosis
• Reduces glucose resorption from kidney; caution in patients with urinary incontinence (UI); may cause or contribute to UI. If UI identified, refer to primary care or geriatrics for further evaluation and management
Second generation sulfonylureas
• May cause hypoglycemia and weight gain, start with low dose glipizide or glimepiride, monitor and titrate
• Useful when drug cost is important (generics available)
• Do not use glyburide  which is long acting and has numerous drug interactions
• Evolving concern on cardiovascular safety
Basal insulin for patients who are not eligible or amenable to any of the above options
• Start 0.2 units/kg/day, monitor and titrate 
• Older patients with new onset diabetes and HbA1c above 10 %; patients may not fully respond to oral agents. Start basal insulin and preprandial short-acting insulin
Or 7.0–8.0 %
As long as no hypoglycemic events
DPP-4 inh (same as above)
GLP-1 RA (same as above)
SGLT-2 inh (same as above)
Insulin: as above
Or 8.0–8.5 %
And up to 9 % in selected cases unlikely to benefit from lower values, due to limited life expectancy
Most non-insulin antihyperglycemic agents will require to be stopped due to limitations in renal excretion and disease status
• Insulin basal bolus and preprandial
• Daily home skilled nursing services not feasible long term
• Basal insulin plus oral agents, as long as glycemic target can be achieved
• Use alternatives to insulin if the patient/caregiver cannot check glucose or inject insulin 4 times/day
• Most patients with advanced chronic kidney or liver disease require insulin, due to risks, lack of evidence, unpredictability, or contraindications to non-insulin options.
• Insulin can be challenging, if caloric intake fluctuates, for procedures, e.g. hemodialysis, etc.
DPP-4 inhibitor alone (reduces HbA1c by 0.7 %) consider when this may be sufficient to reach target
DPP-4 inhibitor plus Alpha glucosidase inhibitor (if tolerated)
Long-acting GLP-1 RA (weekly), if effective and safe, may be convenient in certain settings, especially when the patient requires assistance with medications
• Avoid glucose values above 220 mg/dl, since this can be associated with glycosuria (dehydration and UI).
• Not only avoid glucose values close to 100 mg/dl, but if a trend towards these values is detected, a decrease in the intensity of regimen may be required, before a hypoglycemic event occurs.
• Avoid weight loss, which will be mostly be from muscle and bone mass, due to low physical activity levels in many of these patients
The reader is also referred to Chap. 25, Nephrology.
22.5.3 Geriatric Syndromes and Diabetes
Geriatric syndromes are prevalent in older adults, associated with aging and comorbidities, and often lead to poor quality of life, loss of independence, and admission to long-term care facilities . These syndromes include cognitive decline, depression, persistent pain, polypharmacy, urinary incontinence, and reduced mobility and falls. Some of these may impair diabetes self-management, lead to poor glycemic control , and increase the risk for hypoglycemia especially those described below .
In prescribing for an older person with diabetes, it is important to recognize that older people may carry chronic diseases from earlier life, as well as develop new diseases, and that multimorbidity leads to being prescribed a great number of medications, with higher risk for drug–drug or drug–disease interactions. In addition, adherence to medications declines as the number of medications and the frequency of dosing increases. Polypharmacy in older people with diabetes has also been driven by pay-for-performance and the use of HbA1c as a quality outcome measure . Often when providers follow guidelines for a series of conditions, the result is polypharmacy. Guidelines are not based on studies of patients with multimorbidity . The recent shift toward quality outcomes that include reduction of polypharmacy by incorporating age- and patient-specific factors to assess quality and performance should lessen medication burden .
The American Geriatrics Society published the “Beers criteria,” a list of medications that should be avoided or used with caution in older patients . Among them, Glyburide is listed as a drug to avoid, as it is associated with a high risk for hypoglycemia due to its long half-life. While sulfonylureas may have decreased due to new alternative agents, it these agents are still sometimes useful. While glyburide ought to be avoided other sulfonylureas (like glipizide or glimepiride) are acceptable . Similarly the routine use of regular insulin sliding scale is discouraged by the Beers Criteria in older adults with diabetes. Table 22.2 presents an overview of pharmacologic options, and considerations in the geriatric population.
188.8.131.52 Cognitive Impairment
There is epidemiological evidence that diabetes increases risk for cognitive impairment [27, 28]. Long-standing diabetes may contribute to the development of dementia, however there are insufficient longitudinal studies to address the impact of patient attrition (i.e., patients with diabetes may not live long enough to develop dementia). The Atherosclerosis Risk in Communities study showed the association between diabetes in midlife and long-term cognitive decline , suggesting that diabetes prevention and control in midlife may protect against cognitive decline later in life.
Poor glycemic control with recurrent especially severe hypoglycemic events is independently associated with accelerated late-life cognitive decline , and there is no evidence that more intensive glycemic control will slow progression towards dementia.
The Memory in Diabetes study (ACCORD MIND) evaluated patients with type 2 diabetes with a mean age 62.5 years, and showed no benefit from intensive glycemic or blood pressure interventions on cognitive testing . Similarly, an ancillary analysis from the Look AHEAD study showed no benefit in cognitive function after 8 years of intensive lifestyle intervention in adults with obesity and type 2 diabetes . Studies in older adults at high-risk or with newly diagnosed type 2 diabetes may provide better understanding on the potential benefits of earlier interventions to reduce the risk of cognitive decline and preserve function in these patients.
Hypoglycemia in older adults with type 2 diabetes is associated with increased risk for cognitive decline and dementia . Conversely, a post-hoc analysis in the ACCORD study showed that poor cognitive function may increase the risk of severe hypoglycemia . These points emphasize the importance of incorporating cognitive assessment as pertinent to refine a treatment plan and to avoid hypoglycemia in the older adult with diabetes.
The reader is referred to Chap. 8, Office Tools for Assessment for recommendations on screening for cognitive impairment.
22.5.4 Challenges with Insulin Use
Due to the progressive natural history of type 2 diabetes, most patients will eventually require insulin. However, the dexterity and ability needed to implement an insulin regimen could be affected by neuropathy, arthritis, cognitive impairment, and other comorbidities. If self-management skills are limited, then providers should assess the availability of informal (i.e., family or friends) or formal (e.g., home health nursing) support to implement and monitor an insulin regimen. In addition, documenting in the patient’s record the presence of these chronic conditions and comorbidities will help providers reach the level of complexity needed for appropriate clinical reimbursement and facilitate coordination of care for older adults with diabetes on insulin.
22.5.5 Challenges with Obesity Management
The prevalence of obesity and its comorbidities increase with age . Obesity could impact the medical (e.g., type 2 diabetes, cardiovascular disease, and cancer), mental (e.g., depression and dementia), social (e.g., stigmatization and isolation), and functional domains (e.g., impaired mobility) in the geriatric population [36–39]. However, the assessment and management of obesity in older adults with diabetes may not be common practice among providers. One contributing factor may be the limited evidence on potential benefits associated with weight loss medications and bariatric surgery in older adults. However, modest intentional weight loss through lifestyle (healthy nutrition and increased physical activity) could reduce the burden of obesity-related comorbidities and improve the quality of life of otherwise healthy obese older adults .
The “obesity paradox ” is a term used to describe the fact that better outcomes are seen in older people at higher BMIs compared to younger people [40–42]. Epidemiological studies have described better survival in overweight older adults with heart failure, hypertension, stroke, and end-organ damage. However, better outcomes are also seen in each BMI category, when better fitness was also present [41, 43, 44] suggesting that fitness and not simply fatness is important. Therefore, it is important that cardiovascular and physical conditioning with modest weight management should be a part of the plan of care in older patients with diabetes. In Case 1, Mr. F. who has a BMI of 29 kg/m2 would benefit from the lifestyle interventions consisting of exercise, and modest intentional weight loss. He may lose 10 lb in 1 year, and lower his BMI to 28 kg/m2. While remaining in the overweight group, he has likely improved his clinical, metabolic, and functional profiles.
22.6 Osteoporosis and Bone Metabolism
Osteoporosis increases with age but there are potential gender differences in its consequences. Osteoporosis-related fractures are more common in older women, probably related to accelerated bone loss in the postmenopausal period, but mortality is greater in older men within the first year after a hip or femoral fracture [45, 46]. In addition, the prevalence of osteoporosis increases in the oldest old (age 80 and older), in whom the average T-score is lower than −2.5 SD. Furthermore, more than 50 % of patients admitted to a hospital with hip fracture belong to this age group [47, 48].
Among non-communicable chronic diseases, osteoporosis is fifth in disability burden behind coronary heart disease, lung disease, osteoarthritis and Alzheimer’s dementia . Therefore, timely assessment and appropriate therapy could reduce the growing burden associated with osteoporosis.
22.6.1 Osteoporosis Screening
Current guidelines provide recommendations for osteoporosis screening for both women (age 65 and older with or without risk factors) [50, 51] and men (age 70 and older with risk factors) [52, 53]. Approximately 50 % of women and 20 % of men are at risk for an osteoporosis-related fracture during their lifetime. Osteoporotic fractures accelerate functional decline in older adults and have major economic impact [54, 55]. The annual costs of incident fractures are estimated at $ 17 billion with men accounting for 29 % of fractures and 25 % of costs. An economic model incorporating the growth of the older adult population projected that by 2025 the annual fractures and costs will increase by 50 % . Forty percent of people who break their hip do not fully recover to their functional level before the fracture and 20 % have such major functional decline that independence is lost and long-term care placement may result .
Prevalence studies find nearly half of all women age 80 and older have a vertebral fracture . Additionally, older adults with vertebral fractures present with progressive height loss, pain, loss of mobility and independence, psychological distress, decreased quality of life, and increased risk of disability [57–59]. Furthermore, patients with vertebral fractures also have increased risk for non-vertebral fractures.
22.6.2 Osteoporosis Risk Assessment
In addition to age-related decline in bone, the loss of gonadal function in both women and men, and conditions associated with inflammation may contribute to increased risk of fracture [60–62]. In the World Health Organization (WHO) Fracture Risk Algorithm (FRAX® , available at www.shef.ac.uk/FRAX/), increasing age is one of the strongest predictors for fracture risk, only second to personal history or family history of previous fragility fracture. Of interest, there is a remarkable variation in the age-specific risk for fracture worldwide. In the 45 countries studied, there was greater heterogeneity between countries than between gender differences within a country . A revision of FRAX (3.0) uses updated epidemiological information in the USA and shows the predictive value for hip fracture even in men and women age 70 and older .
Data from the Osteoporotic Fractures in Men Study (MrOS), suggests that pharmacologic treatment would be needed in one-third of USA; white men aged 65 years and older and one-half of those aged 75 years and older . A practical approach to screening for men is to address height loss, especially if ~1.5–2 in., as potentially associated with asymptomatic vertebral fractures . Additional clinical risk factors that should prompt earlier screening include low body weight, history of prior fragility fracture, family history of osteoporosis, smoking, excessive alcohol intake, and long-term use of high-risk medications (e.g., glucocorticoids at doses >5 mg/d of prednisone, or its equivalent) .
22.6.3 Special Considerations in Older Adults
Falls, sarcopenia, and frailty are not included in FRAX, but they are associated with increased fracture risk in older adults [67–74]. In addition, more than 50 % of people hospitalized due to hip fracture are older than 80, and many of those will sustain another fracture [47, 75–78] For patients with spine and hip fractures, there is a broad body of literature supporting the reduction of fracture risk from pharmacological treatment . In general, these medications are safe in the older population as long as pertinent precautions are followed. For instance, in older adults with CKD stages 4 and 5 bisphosphonates are contraindicated, and proper monitoring is required to avoid adynamic bone disease [79, 80] (see also Chap. 25, for a discussion of metabolic bone disease.) However, the alternative antiresorptive monoclonal antibody denosumab could be considered.
Before starting either type of antresorptive therapy , examination of the oral cavity by a dental professional is indicated. This is especially important in the older people who are at greater risk for oral disease (poor dentition requiring dentoalveolar surgery, tooth extraction, dental fractures) and poor oral health (including periodontal disease, caries, infections) . Oral disease increases risk of osteonecrosis of the jaw. While most cases have been reported after IV formulation in frail older adults with multimorbidity and/or history of malignancy, it is recommended to treatment dental diseases prior to beginning antiresorptives .
In addition, calcium and vitamin D supplementation and exercise (see below) are important in prevention and management of osteoporosis [83, 84]. The recommended calcium intake for older adults is 1200 mg per day, ideally from dietary sources [50, 52, 84, 85]. The National Institutes of Health offer a fact sheet for calcium supplementation, with detailed information on dietary sources of calcium (available at ods.od.nih.gov/factsheets/Calcium-HealthProfessional/#h3). However, the dietary intake of calcium in older adults is usually insufficient (about 600 mg per day), thus prescription supplementation is often required to reach the target (additional 500–600 mg per day). Furthermore, older adults have an increased prevalence of chronic or atrophic gastritis, with achlorhydria, leading to malabsorption of calcium . Therefore, some experts suggest calcium citrate over calcium carbonate . Constipation may develop with either, and it is important to advise proper hydration and measures to avoid this geriatric syndrome. Concomitant intake and maintenance of proper vitamin D is required to ensure calcium absorption. However, older adults commonly have low levels of 25 hydroxyvitamin D (25OHD) and, in spite of reports of measurement inconsistencies [88, 89], this should be measured. Vitamin D supplementation is recommended when levels are below 30 ng/ml, aiming to maintain levels above 35 ng/dl using D3 (cholecalciferol) [90, 91]. Toxicity is rare, as vitamin D has a wide therapeutic range. Additional potential benefits of vitamin D repletion include reduction of falls and improvement of physical function [51, 89, 91].
There is evidence of the effectiveness of exercise to preserve or improve bone mass and also to reduce falls [92–94]. Falls are reduced particularly with the combination of aerobic, flexibility, resistance and balance training. Exercise recommendations must be tailored, especially for those with severe osteoporosis, who should avoid forward flexion exercises, using heavy weights, or side-bending exercises, because pushing, pulling, lifting, and bending exert compressive forces on the spine that may lead to fracture. These patients may benefit from specific recommendations provided by a physical therapist . For the majority of older patients, at risk for or with osteoporosis, resources include the National Institute on Aging Go4Life program, which offers free education materials (available at go4life.nia.nih.gov)  and the National Council on Aging, which lists a number of evidence-based programs (available at www.ncoa.org/center-for-healthy-aging/physical-activity/physical-activity-programs-for-older-adults/) .
For primary prevention of fractures, a patient with known osteoporosis should have an assessment of gait and balance, especially if there is a history of falls. For details see Chap. 8 on Office Based Assessment. While not specific to osteoporosis, the practice guidelines from the American Geriatrics Society and the British Geriatrics Society  outline recommendations for older adults who present with the falls syndrome. Patients with osteoporosis may benefit greatly from a multifactorial risk assessment for falls if they present with more than 2 falls per year, or if a fall leads to an injury or is the chief complaint in the clinical visit. The endocrinologist should ask about falls, and refer the patient to a geriatrician or to a falls clinic. Prevention of falls plays a major role in the prevention of morbidity in patients with osteoporosis. The CDC Stopping Elderly Accidents, Deaths & Injuries (STEADI) program offers tools for assessment and prevention of falls (available at www.cdc.gov/steadi/) . Furthermore, for patients at high risk for falls, home safety assessment and modification in those with a previous fall can reduce the rate of falls and risk for falling .
Regarding secondary prevention, it is important to recognize patient characteristics that are associated with greater risk for a subsequent fall. A recent systematic review and meta-analysis found that female, institutionalization, decreased vision , dizziness, dementia, cardiac and respiratory diseases, in addition to osteoporosis, increased the risk for a second contralateral hip fracture . Special attention ought to be placed for secondary prevention in those cases.
22.6.4 Problems with Calcium Metabolism
The incidence and prevalence of primary hyperparathyroidism (PHP) is greater with aging. Similarly, the prevalence of cancer associated with non-parathyroid hormone dependent hypercalcemia also increases with aging. For PHP, advanced age is not a contraindication for parathyroidectomy; however, assessments of function, cognition, life-expectancy, and other age-related conditions are needed to complete the assessment and recommendation towards surgery, or chronic medical management with a calcimimetic (Cinacalcet) , as well as the pertinent interventions for diagnosis and management of secondary osteoporosis, falls and fracture prevention.
Older adults are a heterogeneous population with a range of comorbidities that influence treatment in all illnesses including calcium disorders. If 10 years passes and PHP is found in Mr. F. (Case 1) who is now 88 years old, with well-controlled diabetes, and preserved physical and cognitive function, parathyroidectomy will be the procedure of choice. However, for Mrs. B. (Case 4), now 82 years old, with cardiovascular disease, severe heart failure, advanced dementia and poor physical function, parathyroidectomy may not be applicable, and medical management may be the first option to discuss with her family .
22.7 Thyroid Disorders
Thyroid disorders are common in older adults with clinical presentations that include both long-standing and new-onset illnesses. Clinical and subclinical hypothyroidism and hyperthyroidism are common as thyroid nodular disease and differentiated thyroid cancer (DTC) .
The incidence of hypothyroidism (defined as high TSH and low T-4) increases with age as a result of long-standing hypothyroid disease, resulting from the treatment for hyperthyroidism and differentiated thyroid cancer (DTC), or as a side effect of amiodarone therapy. Diagnosis of hypothyroidism can be delayed by comorbidities, including depression and cognitive decline, thus proper screening must be implemented.
Thyroid hormone replacement with levothyroxine (LT4) is usually based on lean body mass (~1.6 mcg per kg-weight) for healthy middle age patients ; age-related loss of lean body mass  often means dose adjustments are needed with increasing age. In addition, lower starting dosages (25–50 mcg per day) is recommended for healthy older adults, lower (12.5–25 mcg per day) for those with known or possible cardiovascular disease. Replacement therapy must strive to avoid overtreatment, with careful monitoring every 4–6 weeks, and dose adjustments of 12.5 mcg, until TSH target is reached. A start and go slow approach may also provide more stable TSH values over time [102, 104, 105].
For a patient with a clinical presentation similar to Mr. F. (Case 1), who is otherwise healthy and recently developed primary hypothyroidism, LT4 therapy could reach a full dose replacement similar to a younger person. In contrast, for a patient similar to Mrs. B. (Case 4), a more careful approach is required, given concerns for bone and cardiovascular risk.
Guidelines recommend TSH targets between 1 and 2.5 mIU/L, but normal age-specific TSH values are higher in older adults when compared with younger people . The NHANES study has shown that the 97.5 centiles for TSH in the 20- to 29-year and the 80-year and older groups were 3.56 and 7.49 mIU/L, respectively and 70 % of older patients with TSH greater than 4.5 mIU/L were within their age-specific reference range . In addition, some suggest that higher TSH values in healthy older individuals might be associated with better cognitive and physical function [107, 108].
While there are no randomized controlled trials, we recommend caution when treating hypothyroidism in older adults, especially in the oldest old. A TSH closer to 2.5 mIU/L, and perhaps higher (within the normal range) may be more appropriate, whereas reaching TSH of 1 mIU/L may be potentially harmful.
In addition, for older adults with hypothyroidism related to Hashimoto’s thyroiditis, it is important to be aware of the risk of autoimmune atrophic gastritis , given potential clinical implications for nutrition and pharmacologic therapies.
22.7.2 Subclinical Hypothyroidism
This condition is defined as a high TSH and normal T-4. The European Thyroid Association provides guidelines for subclinical hypothyroidism management  with two potential scenarios: the first one with TSH values range between the upper limit of normal and 10 mIU/L, and the second when TSH is greater than 10 mIU/L. About 90 % of cases fall in the first scenario  and have milder clinical consequences [112, 113].
Guidelines recommend careful monitoring and a watchful waiting in the oldest old , avoiding a rush to diagnosis based on one value and rather rechecking TSH at 3–6 months intervals.
A recent systematic-review assessed the risk of stroke in those with subclinical hypothyroidism . Compared to those with normal thyroid function, no increased risks were found in individuals with subclinical hypothyroidism in those aged 65 and older. A subsequent analysis from this research group suggested a pattern of increased risk for fatal stroke in younger individuals with higher TSH concentrations .
Increased risk for depression has been reported in subjects older than 60 years with untreated subclinical hypothyroidism , while a more recent prospective study in adults age 70–82  did not show an association of subclinical hypothyroidism with increased depressive symptoms among those at high cardiovascular risk.
Regarding cognitive decline, a recently published meta-analysis  found no association between subclinical hypothyroidism and cognitive performance (impaired mini-mental state examination, executive function, and memory).
Regarding quality of life, a small randomized trial compared the impact of thyroid hormone replacement versus placebo in adults who screened positive for hypothyroidism and those with subclinical hypothyroidism. They found improved quality of life (less tiredness) for the hypothyroid  but not those with subclinical hypothyroidism. Therefore, clinical judgment is crucial in the management of subclinical hypothyroidism in older adults. Caution with over-screening leading to overtreatment has been raised, particularly if age-adjusted normal limits of TSH are not used . Decisions should include a specific evaluation of the pre-existent cardiovascular risk, degree of TSH elevation, comorbidity, and frailty .