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Pharmacologic and Exercise Considerations in Older Adults With Diabetes

Wenker, Susan L., PT, PhD; Walbrandt Pigarelli, Denise L., PharmD, BC-ADM

Topics in Geriatric Rehabilitation: January/March 2019 - Volume 35 - Issue 1 - p 31–41
doi: 10.1097/TGR.0000000000000214
Pharmacology for the Older Adult: A Primer for the Fine Print

Diabetes mellitus affects approximately 25% of United States adults aged 65 years and older, and the disease often complicates the aging process. Diabetes management requires attention to 3 treatment modalities: exercise, medical nutrition therapy, and medications. The main objective when working with patients who have diabetes is to optimize life while providing interventions to minimize organ system impairment, which may cause reduced body function and, subsequently, decreased life participation.

Department of Family Medicine, School of Medicine and Public Health, University of Wisconsin-Madison Doctor of Physical Therapy Program (Dr Wenker); and University of Wisconsin-Madison School of Pharmacy, and Diabetes Clinic, William S. Middleton Memorial VA Hospital, Madison, Wisconsin (Dr Walbrandt Pigarelli).

Correspondence: Susan L. Wenker, PT, PhD, Department of Family Medicine, School of Medicine and Public Health, University of Wisconsin-Madison Doctor of Physical Therapy Program, 5170 Medical Sciences Center, 1300 University Ave, Madison, WI 53706 (wenker@pt.wisc.edu).

The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Approximately 12.2% of US adults have diabetes mellitus, which equates to about 30.3 million people.1 The disease is more prevalent in older adults; roughly, 25% of US adults aged 65 years or older have diabetes. In addition, the estimated annual excess health care expenditure for adults older than 65 years who have diabetes is $11 825 greater as of 2012 compared with older adults without disease.2 Management of diabetes is based on the foundations of medical nutrition therapy, medications, and exercise. Moreover, physical therapy can be an important intervention to assist with the exercise component while promoting patient safety.

Physical therapists need to use language that is reflective of current recommendations. Common language across health professions is important when documenting patient care and when communicating with patients and other health care providers. Over the years, terminology associated with diabetes has changed, given preferences of and recommendations by the American Diabetes Association (ADA) and other professional and patient advocacy organizations. Table 1 contains a list of terms and definitions that are preferred. Table 2 describes the 3 levels of hypoglycemia.6 Finally, terms associated with diabetes classifications include type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

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CASE PRESENTATION

This case study provides an example of the interconnectedness among medications, nutrition considerations, and exercise.

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Chief complaint

“I have had diabetes for about sixteen years. I would like to start exercising but I am afraid I may have troubles because of my medications.”

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History of present illness

Sarah Martin is a 66-year-old woman who comes to physical therapy to develop a home exercise program; however, she is fearful of falling. She has gained 10 lb over the past year despite attempts to independently change her diet and exercise. Sarah monitors her blood glucose once a day at varying times, and her results range from 190 to 220 mg/dL.

Sarah's goals:

  1. Walk through the grocery store without assistance.
  2. Improve blood glucose values
  3. Prevent falls
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Past medical history

T2DM × 16 years

Hypertension × 17 years

Dyslipidemia × 12 years

Morbid obesity × 20 years

Bilateral knee osteoarthritis

Unsteady gait

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Social history

Sarah has been married for 40 years, and her 2 children live an hour away with families of their own. She is recently retired from a career as a sales associate in a call center. She denies any use of tobacco products since stopping smoking 10 years ago but does drink alcohol occasionally (3 beers or glasses of wine per week). Sarah has been using a single-point cane for the past year whenever she is away from home.

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Nutrition information

First meal at 7 AM: 2 eggs, 2 whole wheat toast with homemade jam, 8-oz skim milk, and 8-oz black coffee

Second meal at noon: meat sandwich with 1 slice bread, fruit, corn chips, and water

Third meal at 6 PM: grilled skinless chicken breast, corn, lettuce salad, whole wheat bun, and 8-oz skim milk

Snacks: grazes on chocolate candies, graham crackers, and potato chips throughout the day and evening

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Medications

Aspirin 81 mg orally (po) once daily

Atorvastatin 40 mg po once daily

Glipizide 10 mg po twice a day (bid) with food

Hydrochlorothiazide 25 mg po once daily

Lisinopril 20 mg po once daily

Metformin 1000 mg po bid with food

Allergies: Penicillin—hives

Concepts within the case study will be addressed throughout this article.

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Diabetes ABC goals

As an overview, biochemical and physical manifestations of diabetes are managed through prevention and treatment strategies to reduce risk for negative patient-oriented outcomes such as atherosclerotic cardiovascular disease (ASCVD), amputations, dialysis, and so forth. To this end, diabetes ABC (hemoglobin A1C/glycemia, blood pressure, cholesterol/lipid) goals may be identified to reduce risk for long-term disease complications. Goals should also minimize short-term adverse health outcomes such as hypoglycemia and hypotension.

For older adults with diabetes, the ADA recommends considering the person's overall health status when determining ABC goals (Table 3).7

TABLE 3

TABLE 3

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SELECTED MEDICATION CONCEPTS

This section will discuss commonly used pharmacological therapies used in older adults with diabetes. Often, older adults likely take several medications to manage the diabetes ABCs as well as take low-dose, daily aspirin for primary or secondary prevention of ASCVD. Furthermore, more than 1 medication may frequently be required to manage glycemia and blood pressure. The following will group these medications to facilitate an improved understanding pharmacotherapy.

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Glucose-lowering therapies

Of the 10 categories of glucose-lowering agents available in the United States, 6 are likely to be commonly encountered in daily physical therapist (PT) practice (Table 4). Older adults with diabetes may refer to products by either generic or brand name and may need to have therapy adjusted, given other health conditions, cognitive function, or ability to afford medication. Assessment of hypoglycemia risk is critical for PTs to consider when assisting any patient with diabetes and especially older adults. Appraisal of nutritional intake prior to exercise/activity, current blood glucose values, and historical response to exercise would be prudent to know in addition to monitoring physiologic status prior to, during, and after exercise.

TABLE 4

TABLE 4

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Oral medications for type 2 diabetes

Metformin is a requisite medication for most older adults with type 2 diabetes.7 It should be dosed appropriately according to kidney function and discontinued if a person has advanced kidney disease.8 The main adverse effects are gastrointestinal intolerance and may include fecal incontinence; however, sustained-release preparations are available, which may help manage these effects. People with concomitant heart failure may also require additional monitoring for safety if using metformin.

Sulfonylureas and meglitinides are still commonly prescribed in older adults but less so than they were about 10 or 15 years ago.9–11 This trend is likely related to hypoglycemia frequency and, subsequently, falls risk. Glipizide is preferred to other sulfonylureas in older adults, given a lower risk of hypoglycemia; meglitinides such as repaglinide or nateglinide may be chosen because of a shorter duration of action resulting in a lower risk of hypoglycemia overall. However, low blood glucose may occur at any dose with any of these agents.

Thiazolidinediones may be used with caution in older adults with diabetes. Although effective for blood glucose control with a low risk for hypoglycemia, these medications may cause lower extremity edema (which will not respond to diuretics) and may need to be avoided in people with concomitant heart failure. Fracture risk with this class of medications is of special concern for older adult women at high risk of fracture.12

The α-glucosidase inhibitors acarbose and miglitol do not generally cause hypoglycemia, but many (though not all) adults experience gastrointestinal intolerance from them. The main adverse effects are abdominal bloating, flatulence, and more frequent stools, which may be loose or liquid in consistency. The A1C-lowering effect of these medications is less than other drug classes although the greatest clinical benefit is of lowering postprandial blood glucose.

Dipeptidyl peptidase-4 inhibitors are frequently prescribed because they are well tolerated overall and have a low risk of hypoglycemia. However, published data reveal a signal for increased risk of hospitalization for heart failure with some agents in this class.13 Moreover, these medications are not available as generics, and cost may be a barrier for some older adults.

Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have significant adjunct benefits of blood pressure lowering, decreased weight, and secondary ASCVD prevention. Conversely, the agents are expensive and may cause increased urination, genital mycotic infections, urinary tract infections, dizziness, and orthostatic hypotension. Adults older than 65 years are more likely to have reduced medication efficacy, similar decreases in body weight, and greater decreases in blood pressure than younger adults.14

Although all medications have side effects, unique SGLT-2i adverse effects are important to note. Agents in this class have been associated with euglycemic ketoacidosis described as normal or mildly elevated blood glucose (<250 mg/dL). Nausea, vomiting, shortness of breath, and malaise may also occur. Table 5 includes factors associated with increased euglycemic ketoacidosis risk.15

TABLE 5

TABLE 5

Bone and fracture concerns are associated with canagliflozin and dapagliflozin. Canagliflozin has been linked to more frequent fractures than placebo, and the increased risk is evident as early as 12 weeks after starting canagliflozin therapy.16 , 17 Often minor trauma such as a ground-level fall can cause fractures. Decreased bone mineral density with canagliflozin has been noted at the hip and lower spine as compared with placebo.17 Furthermore, dapagliflozin has been associated with bone demineralization and fracture in people with concomitant, moderate kidney disease.18

Finally, canagliflozin has been related to a 2-fold increased risk of lower limb amputations even in people without other risks for amputation.19 The most frequent sites for these amputations are the toe and the mid-foot; some people experienced multiple amputations. The cause for this increased risk is currently unknown.

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Injectable agents

Injectable agents must be carefully considered in older adults. Vision, dexterity, cognition, and caregiver availability may affect if and how these agents are prescribed.

The glucagon-like peptide-1 receptor agonists reasonably lower A1C in people with type 2 diabetes but are also associated with nausea, vomiting, and diarrhea. These adverse effects usually decrease in severity and frequency over the first 4 weeks of therapy; weight loss may occur. Although hypoglycemia risk is low, cost is high with these agents.

Insulin has the greatest A1C-lowering potential for people with diabetes. However, safety issues may limit insulin's utility in older adults. Hypoglycemia is the most common adverse effect with any insulin, and falls risk must be considered both in and outside of the home. Basal insulin therapy entailing a single, daily injection should be considered instead of multiple daily injections whenever possible.7

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Blood pressure therapies

Adults with diabetes may commonly require more than 1 medication to reach blood pressure targets.20 Medication selection is often based on whether or not the person with diabetes has a compelling indication such as a urinary albumin-to-creatinine ratio of 30 mg/g or greater, in which case an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker is preferred. Compelling indications for β-blockers include heart failure, history of myocardial infarction, or angina. Recommended first-line agents for persons without compelling indications include an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, dihydropyridine calcium channel blocker, or thiazide-like diuretic (Table 6). Multidrug antihypertensive regimens may combine 2 or more first-line agents or incorporate medications from other drug classes. For additional information, the reader is directed to review the hypertension treatment algorithm in the cardiovascular disease and risk management position statement in the annual ADA's Standards of Medical Care.20

TABLE 6

TABLE 6

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Lipid management therapies

Statin therapy in addition to lifestyle management is recommended for adults older than 40 years with diabetes to help decrease ASCVD risk, although the strength of recommendation depends upon (1) whether the individual has preexisting ASCVD and (2) the age of the person.20 For people with diabetes who have preexisting ASCVD, high-intensity statin therapy is recommended and well supported in the medical literature. For individuals without ASCVD, moderate-intensity statin therapy is recommended for those aged 40 to 75 years (well supported) as well as for individuals older than 75 years (less well supported) (Table 7). Combination lipid therapy may be appropriate for individuals who do not achieve adequate low-density lipoprotein lowering, though statin combination with a fibrate or niacin is generally not recommended (well supported).

TABLE 7

TABLE 7

Unusual muscle discomfort and weakness are possible adverse effects of statins, which require further assessment by the statin prescriber. If discomfort or weakness actually is associated with the statin, various management strategies may be trialed such as assessing for drug interactions, switching to a different statin, ascertaining vitamin D and thyroid status, or dosing the statin less than daily. Because muscle symptoms may affect balance, falls risk, and ability to be active and engaged in exercise, it is important to refer muscle concerns to the statin prescriber for consideration of appropriate management.

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Aspirin

Similar to statin therapy, aspirin recommendations for ASCVD risk reduction are based upon whether a person with diabetes already has ASCVD or not.20 For individuals with ASCVD, daily aspirin dosed between 75 and 162 mg/d is recommended (well supported). Primary prevention of ASCVD with aspirin for adults aged 50 years and older is controversial. Daily aspirin therapy dosed at 75 to 162 mg/d for primary ASCVD prevention in adults older than 50 years may be considered if a person with diabetes has at least 1 additional major ASCVD risk factor (Table 8).

TABLE 8

TABLE 8

General concepts related to diabetes medications in older adults include minimizing health risks while creating an individualized plan with consideration of medication costs. Physical therapists should especially be aware of medications that may contribute to falls risk such as orthostatic hypotension or urge incontinence as related to safety issues such as quickly answering a telephone or doorbell. Some medications are associated with decreased bone mineral density and fractures as well as increased amputation risk. Optimization of diabetes therapies may require interprofessional collaboration to support patient-centered outcomes.

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Medication resources

It is imperative to be familiar with reputable medication information, given relatively frequent approval of new agents (or agent combinations) and changes in prescribing recommendations due to emerging clinical trial data. Physical therapists may find the following resources helpful for diabetes-related medication information.

The annual Diabetes Care January supplement,5 available via open access at http://care.diabetesjournals.org/content/41/supplement_1 and updated online continuously beginning in 2018, includes 3 position statements that provide evidence-based information: “Pharmacologic Approaches to Glycemic Treatment,”21 “Cardiovascular Disease and Risk Management,”20 and “Older Adults.”7

Online, updated databases are also readily available. Table 9 provides summary details for selected databases.

TABLE 9

TABLE 9

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EXERCISE

Physical therapists recognize the benefits of physical activity and exercise for people of all ages with varying conditions. These terms, physical activity and exercise, are used interchangeably, yet they are different. Physical activity is any body movement that works the muscles and requires more energy than resting. In comparison, exercise is a purposeful type of physical activity that will improve fitness. Physical therapists prescribe exercise, and evidence supports incorporation of exercise for people with diabetes. The following section will discuss special considerations PTs recognize when prescribing exercise to people with diabetes in relation to aerobic and anaerobic exercise, flexibility, and balance. In general, PTs should always consider dose, type of exercise, frequency, duration, and self-management education to promote patient safety.

Patient safety is paramount when prescribing exercises. In addition to monitoring a patient's heart rate, blood pressure, and respiratory rate, PTs should have knowledge of the patient's medications (including dosing), nutritional intake prior to exercise, and blood glucose before, during, and postexercise. Duration, type, and intensity of the exercise will influence these factors differently. Furthermore, glycemic responses to exercise are variable, and the ADA provides guidance for carbohydrate intake prior to exercise based on the anticipated duration and intensity of the exercise.22 Blood glucose between 90 mg/dL and 150 mg/dL may require supplemental carbohydrates depending upon type and duration of exercise and medication on board. Carbohydrate supplementation is unnecessary at the beginning of exercise with blood glucose between 150 mg/dL and 250 mg/dL. Blood glucose more than 250 mg/dL may predispose the person to unsafe hyperglycemia; the decision to exercise is at the discretion of the health care provider.

Monitoring of blood glucose during exercise will mitigate the risks of hyperglycemia and hypoglycemia. Both of these situations are common in people with diabetes. These risks will vary depending on the insulin or insulin secretagogue dose, carbohydrate intake, timing of last meal, and type of exercise.

Exercise benefits differ both by type of exercise and by type of diabetes. For adults with T2DM, routine exercise may improve insulin sensitivity for up to 72 hours postexercise.23 A1C may also improve, especially with increased exercise intensity.24 Activity recommendations to patients with T2DM should be part of routine education since leisure activities that combine jogging, walking, gardening, tai chi, Hula-Hoop, swimming, dancing, and cycling can lower A1C by −0.60%.25 Conversely, well-designed studies have not consistently demonstrated benefits of exercise on A1C in people with T1DM.26

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Aerobic exercise

Similar to other patient populations, people with diabetes are better able to manage their weight, improve cardiovascular and cardiopulmonary fitness, and decrease mortality rates with aerobic exercise.27 Current recommendations by the ADA indicate that most adults with T1DM and T2DM should engage in at least 150 minutes of moderate to vigorous intensity aerobic exercise per week.28 A minimum duration of 10 minutes of aerobic exercise is recommended and ideally 30 minutes per day or more on most days of the week. Furthermore, people with T1DM have experienced decreases in insulin resistance and improved lipid levels and endothelial function.29 People with T2DM may experience a reduction in A1C, triglycerides, blood pressure, and insulin resistance.30 High-intensity interval training (HIIT) has been found to promote rapid enhancement of skeletal muscle oxidative capacity, insulin sensitivity, and glycemic control.31 However, the safety of HIIT in people with T2DM is less conclusive.32 A person with T2DM who wants to participate in HIIT should be clinically stable, have participated in consistent, moderate-intensity exercise before staring HIIT, and be initially supervised by a licensed health care provider.

In addition to type of aerobic activity, duration, frequency, and intensity need to be considered. People with T2DM should exercise for at least 10 minutes and try to increase the duration to 30 or more minutes per day for most days of the week, with a goal of at least 150 minutes per week of moderate intensity.31 In general, recent evidence supports that all individuals, including those with diabetes, should be encouraged to reduce the amount of time spent being sedentary (eg, working at a computer, watching TV) by breaking up bouts of sedentary activity (being stationary for 30 minutes or more) by briefly standing, walking, or performing other light physical activities.

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Anaerobic/strengthening exercise

According to the ADA, older adults without contraindications should perform 2 to 3 sessions per week of resistance exercises on nonconsecutive days.28 Exercises should include at least 1 set (8-10 repetitions) of 5 or more different exercises involving the large muscle groups of the upper and lower extremities. A recommended resistance provides a moderate level of effort (a rating of 5-6 on a scale where zero is resting and 10 is maximal effort).33 More resistance may produce better glycemic control, yet any type of resistance exercise is better than none. Combining aerobic exercise with anaerobic exercise further improves glycemic control; however, strengthening exercises may be the preferred by adults who are obese, sedentary, and of an older age.34 , 35

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Flexibility and balance

Older adults with T2DM have impaired balance, slower reaction time, and increased risk for falls; however, these limitations can improve with strength and balance training.36 There is limited evidence to guide recommendations about frequency or duration of flexibility and balance exercises, yet the American College of Sports Medicine/American Heart Association suggest spending 10 minutes a day in a stretching routine that involves major muscle and tendon groups with a static stretch of 30 seconds and 3 to 4 repetitions per exercise.37 The ADA suggests that flexibility exercises should be completed 2 times per week.28 With regard to balance, individuals with DM should perform balance exercises 2 to 3 times per week, especially if they have peripheral neuropathy. The type of balance exercises may be highly individualized; however, Tai Chi and Wii Fit–based exercises have been shown to be successful in improving balance and decreasing risk of falls.28 , 36

Aerobic and strengthening exercises along with a flexibility and balance program are an important part of a patient's care. Type, dose, frequency, duration, and intensity will impact a person's glycemic response to exercise. Table 10 provides a summary of exercise recommendations for people who have DM.

TABLE 10

TABLE 10

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CASE QUESTIONS

Review of Sarah's case will assist in responding to the following questions.

1. Based on the International Classification of Function model, what would Sarah's problem list include?

  • Based on the history portion of the initial examination, the following hypotheses may be relevant:
  • Health conditions
    • Diabetes: dysglycemia
  • Body functions and structures (impairments)
    • Decreased strength
    • Impaired sensation
    • Impaired integument
    • Decreased range of motion
  • Activity limitations
    • Falls risk
    • Decreased endurance
    • Decreased walking speed
    • Decreased ambulation in the community
  • Restriction in participation
    • Decreased ability to grocery shop independently
  • Contextual factors
    • Environmental
      • Use of cane in the community
      • Already taking medications for blood glucose, blood pressure, and hyperlipidemia
    • Personal
      • Elevated body mass index
      • Motivated to develop home exercise program
      • Desire to improve eating habits
      • Fear of falling

2. How do Sarah's diet and medications relate to her exercise?

Physical therapists and physical therapy assistants should be cognizant of patients' dietary patterns and interactions with medications. Attention to when Sarah last consumed food and what medications she has already taken are important to determine before engaging in therapy. For example, if Sarah has a morning therapy appointment, it would be important to ascertain what she actually ate for breakfast. In Sarah's case, she eats a mixed nutrient meal of proteins and carbohydrates; this would suggest that she has adequate nutrition to tolerate exercise. Sarah's morning medications include aspirin and 2 glucose-lowering drugs. However, only glipizide has the potential to cause hypoglycemia. Therapists need to monitor Sarah's blood pressure before, during, and postexercise since she takes 2 blood pressure medications. Therapists should be mindful of medication side effects and to what extent PTs and physical therapy assistants are able to maximize a person's physical potential while maintaining patient safety. Particular to Sarah, atorvastatin may be associated with unusual muscle pain or weakness. However, exercise can cause muscle soreness that is unrelated to statin tolerability.

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CONCLUSION

Providing physical therapy to people with diabetes requires increased attention to the physical manifestations of the disease as well as therapeutic and adverse effects of medications and the patient's response to exercise. Physical therapists and physical therapy assistants need to be cognizant of patients' pre-exercise nutrition, hypoglycemic signs/symptoms, interventions to treat low blood glucose, and general safety concerns related to changes occurring as a result of diabetes. Monitoring vitals before, during, and after exercise is also important. Patient safety is of primary concern and may be optimized through collaborative care with other health care providers. A comprehensive plan of care to address strength, balance, mobility, and functional limitations to reduce risk of adverse health outcomes while optimizing independence and quality of life is essential.

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References

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      33. Willey KA, Fiatarone Singh MA. Battling insulin resistance in elderly obese people with type 2 diabetes. Diabetes Care. 2003;26(5):1580–1588.
      34. Church TS, Blair SN, Cocreham S, et al Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2010:304(20):2253–2262.
      35. Röhling M, Herder C, Roden M, Stemper T, Müssiq K. Effects of long-term exercise interventions on glycaemic control in type 1 and type 2 diabetes: a systematic review. Exp Clin Endocrinol Diabetes. 2016;124(8):487–494.
      36. Morrison S, Simmons R, Colberg SR, Parson HK, Vinik AI. Supervised balance training and Wii Fit-based exercises lower falls risk in older adults with type 2 diabetes. J Am Med Dir Assoc. 2018;19(2):e7–e185.
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      Keywords:

      diabetes; exercise; older adult; pharmacotherapy; physical therapy

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