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 [25]. 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 [26].

The American Geriatrics Society published the “Beers criteria,” a list of medications that should be avoided or used with caution in older patients [22]. 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.

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 [29], 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 [30], 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 [31]. 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 [32]. 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 [33]. Conversely, a post-hoc analysis in the ACCORD study showed that poor cognitive function may increase the risk of severe hypoglycemia [34]. 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.

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 % [54]. 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 [55].

Prevalence studies find nearly half of all women age 80 and older have a vertebral fracture [56]. 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.

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 https://​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 [63]. 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 [64].

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 [65]. 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 [17]. 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) [66].

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 [50]. 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) [81]. 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 [82].

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 https://​ods.​od.​nih.​gov/​factsheets/​Calcium-HealthProfession​al/​#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 [86]. Therefore, some experts suggest calcium citrate over calcium carbonate [87]. 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 [50]. 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 https://​go4life.​nia.​nih.​gov) [95] and the National Council on Aging, which lists a number of evidence-based programs (available at https://​www.​ncoa.​org/​center-for-healthy-aging/​physical-activity/​physical-activity-programs-for-older-adults/​) [96].

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 [97] 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 http://​www.​cdc.​gov/​steadi/​) [98]. 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 [99].

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 [100]. Special attention ought to be placed for secondary prevention in those cases.

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) [101], 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 .

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 [99]; age-related loss of lean body mass [103] 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 [106]. 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 [109], given potential clinical implications for nutrition and pharmacologic therapies.

This condition is defined as a high TSH and normal T-4. The European Thyroid Association provides guidelines for subclinical hypothyroidism management [110] 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 [111] and have milder clinical consequences [112, 113].

Guidelines recommend careful monitoring and a watchful waiting in the oldest old [9], 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 [114]. 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 [115].

Increased risk for depression has been reported in subjects older than 60 years with untreated subclinical hypothyroidism [116], while a more recent prospective study in adults age 70–82 [117] 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 [118] 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 [119] 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 [120]. Decisions should include a specific evaluation of the pre-existent cardiovascular risk, degree of TSH elevation, comorbidity, and frailty [107].