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Diabetes in Older People

Case Study

Ilana is a 72-year-old female who has had type 2 diabetes for 3 years. She lives with her husband, Noah, and provides daily care for him in their senior’s apartment. She had a myocardial infarction 4 years ago, but recovered well after having 2 stents inserted. She is active participating in water aerobics twice a week, and walking 30 minutes every day. She enjoys her Sunday night suppers with her children and grandchildren.

Ilana is currently taking metformin 1,000mg twice daily for her diabetes. Her most recent A1C is 7.8%, eGFR > 60 mL/min/1.73m². Other medications are: ramipril 10mg once daily, hydrochlorothiazide 25mg once daily, Enteric-coated ASA 81mg once daily, rosuvastatin 20mg once daily.

Question 1: What would be the most appropriate A1C target for Ilana?

A.	≤6.5%
B.	≤7%
C.	7.1 to 8.0%
D.	7.1 to 8.5%

≤6.5%	Incorrect. Ilana has many characteristics that would actually support a target A1C of ≤6.5 %. She could be described as “otherwise well, functionally independent/not frail” with at least a decade of healthy life expectancy and has not had long-standing diabetes, all features which suggest that Ilana should be considered for treatment to the same glycemic targets as younger people with diabetes. However, Ilana is currently quite active with water aerobics (twice a week), walks 30 minutes every day, and provides daily care for her husband. Since Ilana’s current A1C is 7.8 %, she is already reasonably engaged in self-management, and has a possible existing burden of care, a recommended therapeutic plan for Ilana would be to aim for a more realistic target of ≤7.0 %, with the goal of achieving the target in 2 to 3 months. A conversation in 2 to 3 months would further engage Ilana in shared-decision making, during which time a target A1C of ≤6.5 % could reassessed and considered. Of note, unlike Ilana who is “otherwise well, functionally independent/not frail”, in the clinically complex older adult, tight glycemic control markedly increases the risk of hypoglycemia, and possibly frequent asymptomatic hypoglycemia. This increased risk of hypoglycemia appears to be due to an age-related reduction in glucagon secretion, impaired awareness of hypoglycemic warning symptoms and altered psychomotor performance, which prevents the person from taking steps to treat hypoglycemia. In addition to the consequences of a moderate-to-severe hypoglycemic episode which could include a fall and injury, seizure or coma, or a CV event, A1C values <6.5% are associated with an increased risk of fractures. [Reference: Chapter 37: Diabetes in Older People]
≤7%	CORRECT. Ilana is “otherwise well, functionally independent/not frail” with at least a decade of healthy life expectancy, and therefore should be considered for treatment to the same glycemic targets as “most adults with type 1 or type 2 diabetes”. [Reference: Chapter 8: Targets for Glycemic Control; and Chapter 37: Diabetes in Older People]
7.1 to 8.0%	Incorrect. Ilana is neither functionally-dependent nor at higher-risk for hypoglycemia (i.e. on therapy such as insulin or sulfonylureas) which would suggest a higher A1C of 7.1 to 8.0%. Other considerations which would suggest an higher target A1C of 7.1 to 8.0% are diabetes of several years’ duration, and established complications. [Reference: Chapter 8: Targets for Glycemic Control; and Chapter 37: Diabetes in Older People]
7.1 to 8.5%	Incorrect. Ilana is not “frail and/or with dementia”, nor experiencing recurrent severe hypoglycemia and/or hypoglycemia unawareness, nor having limited life expectancy; any of the 3 parameters which would indicate an increased target A1C between 7.1 and 8.5 %. [Reference: Chapter 8: Targets for Glycemic Control; and Chapter 37: Diabetes in Older People]

Reveal Answer

Question 2: With her history of cardiovascular disease, what would an appropriate second line agent be for Ilana? (More than 1 answer is correct. Can you find them all?)

A.	Empagliflozin
B.	Liraglutide
C.	Gliclazide
D.	Saxagliptin

Empagliflozin	CORRECT. Based on the information given, A1C above target, with a history of clinical cardiovascular disease (MI), empagliflozin would be a good option for Ilana. In addition to the SGLT-2 inhibitor class effects including robust blood glucose lowering, possible weight management (not affiliated with weight gain) and not associated with hypoglycemia in monotherapy, empagliflozin can be used to reduce the risk of major CV events AND may confer renal benefit by reducing the progression of nephropathy. Of note, specific to the use of SGLT-2 inhibitors in the older adult population, the following bears consideration: The older person with diabetes may be more susceptible to dehydration and fractures than younger people treated with these agents. Caution patients about their hydration status. The SGLT-2 inhibitor class appears to be slightly less effective in terms of reductions in A1C in the older adult, likely because of lower GFRs in this age group. Also see Which Vascular Protection Medications Are Indicated For My Patient? [Reference: Chapter 13: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults; Chapter 23: Cardiovascular Protection in People with Diabetes; Chapter 29: Chronic Kidney Disease in Diabetes; and Chapter 37: Diabetes in Older People]
Liraglutide	CORRECT. Based on the information given, A1C above target, with a history of clinical cardiovascular disease (MI), liraglutide would be a good option for Ilana. In addition to the GLP-1 receptor agonist class effects including robust blood glucose lowering, possible weight management (not affiliated with weight gain) and not associated with hypoglycemia in monotherapy, liraglutide has demonstrated CV outcome benefit and may be used to reduce the risk of major CV events. Of note, specific to the use of GLP-1 receptor agonists in the older adult population, the following bears consideration: GLP-1 receptor agonists are well-tolerated in the elderly with a similar side effect profile to younger people with diabetes, except that there may be a higher risk of gastrointestintal side effect in the older adult. The efficacy of the GLP-1 receptor agonists with respect to blood glucose, A1C and weight reduction is independent of age. Also see Which Vascular Protection Medications Are Indicated For My Patient? [Reference: Chapter 13: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults; Chapter 23: Cardiovascular Protection in People with Diabetes; and Chapter 37: Diabetes in Older People]
Gliclazide	Incorrect. Sulfonylureas should be used with caution in the older adult because the risk of severe hypoglycemia increases substantially with age. Of note, however, is that if a sulfonylurea option was to be chosen, gliclazide is a preferred sulfonylurea as it is associated with a lower frequency of hypoglycemia and CV events in comparison to glyburide. Similarly, meglitinides (repaglinide and nateglinide), also insulin secretagogues, are associated with a lower frequency of hypoglycemia in the older person compared to glyburide and may be considered in individuals with irregular eating habits. [Reference: Chapter 37: Diabetes in Older People]
Saxagliptin	Incorrect. In the absence of CVD, in older people with type 2 diabetes, DPP-4 inhibitors should be used over sulfonylureas as second-line therapy to metformin, because of a lower risk of hypoglycemia. However, although DPP-4 inhibitors have the advantages in the older adult of being similarly effective and safe in young and older people with diabetes, cause minimal hypoglycemia when used alone (or with metformin) and do not result in weight gain, DPP-4 inhibitors have not demonstrated CV outcome benefit. Note that unlike any other DPP-4 inhibitors, the product monograph for saxagliptin states, under warning and precautions: “Caution is warranted if saxagliptin is used in patients with history of congestive heart failure (especially those patients who have renal impairment and/or history of MI). [Reference: Chapter 28: Treatment of Diabetes in People with Heart Failure; and Chapter 37: Diabetes in Older People]

Reveal Answer

Question 3: Ilana was started on Empagliflozin 10mg once daily and Ilana is seeing you for her follow up consult. Ilana says to you, “I’m happy. I have lost weight and have even been swimming more. I have no real issues except that I do notice that I have been peeing a lot, probably normal for an old lady, and occasionally I get dizzy spells and feel lightheaded at times… but I just steady myself and it passes.” As a reminder, Ilana’s diabetes-related medications are listed below. Lab values collected 1 week before her appointment with you today are A1C 7.2%, eGFR 58 mL/min/1.73m², ACR 2.2 mg/mmol; and her blood pressure based on home blood pressure readings range from 108/62mmHg to 118/78mmHg.

Metformin 1,000mg twice daily
Empagliflozin 10mg once daily
Ramipril 10mg once daily
Hydrochlorothiazide 25mg once daily
Rosuvastatin 20mg once daily
Enteric-coated ASA 81mg once daily

Which of the following is the most appropriate action for Ilana?

A.	Discontinue the Empagliflozin due to frequent urination, eGFR below 60 mL/min/1.73m², and possible adverse effects/hypoglycemia manifesting as dizzy spells and light-headedness.
B.	Reduce the metformin to 500mg twice daily based on eGFR below 60 mL/min/1.73m²
C.	Reduce/discontinue the hydrochlorothiazide based on home blood pressure readings and symptoms of dizzy spells, light-headedness and frequent urination
D.	Reduce/discontinue the ramipril 10mg based on home blood pressure readings and symptoms of dizzy spells and lightheadedness
E.	Increase the empagliflozin from 10mg to 25mg once daily as Ilana is not at target A1C and is experiencing polyuria due to hyperglycemia

Discontinue the Empagliflozin due to frequent urination, eGFR below 60 mL/min/1.73m², and possible adverse effects/hypoglycemia manifesting as dizzy spells and light-headedness.	Incorrect. Ilana complains of dizzy spells, light-headedness and frequent urination. While all three of these symptoms can be associated with the SGLT-2 inhibitor class, Ilana is on other agents that should be considered for discontinuation prior to empagliflozin. Ilana’s home blood pressure readings and the fact that the symptoms resolve quickly with no other intervention other than a short pause, as well as the fact that the antihyperglycemic agents that Ilana is taking have a low association with hypoglycemia, suggest that her symptoms are due to low blood pressure, rather than hypoglycemia. Ilana is taking three agents that can lower blood pressure: Empagliflozin, ramipril and hydrochlorothiazide. Because empagliflozin has additional vascular and renal protective benefits beyond blood pressure lowering, and because Ilana is most likely also benefiting from the blood glucose lowering effect of the SGLT2- inhibitor, empagliflozin is not the most appropriate agent to discontinue at this time. Notably, Ilana should also be checked for the presence of a urinary tract infection (UTI) as a UTI could also result in symptoms of dizziness, light-headedness and frequent urination. Further to UTIs occurring more frequently in the older adult, UTIs are also a possible adverse effect of the SGLT-2 inhibitor class. [Reference: Chapter 13: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults; Chapter 23: Cardiovascular Protection in People with Diabetes; Chapter 26: Treatment of Hypertension; and Chapter 29: Chronic Kidney Disease in Diabetes]
Reduce the metformin to 500mg twice daily based on eGFR below 60 mL/min/1.73m²	Incorrect. Although is it good practice to always consider adjusting medication doses in the presence of chronic kidney disease, reducing the dose of metformin from 1,000mg twice daily to 500mg twice daily (for example) due to an eGFR 58 mL/min/1.73m², is not likely to resolve Ilana’s symptoms of dizzy spells, light-headedness and frequent urination. Ilana’s home blood pressure readings and the fact that the symptoms resolve quickly with no other intervention other than a short pause, as well as the fact that the antihyperglycemic agents that Ilana is taking have a low association with hypoglycemia, suggest that her symptoms are due to low blood pressure, rather than hypoglycemia. [Reference: Chapter 13: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults; and Chapter 37: Diabetes in Older People]
Reduce/discontinue the hydrochlorothiazide based on home blood pressure readings and symptoms of dizzy spells, light-headedness and frequent urination	CORRECT. Ilana is experiencing dizzy spells, lightheadedness and frequent urination. All three of these symptoms can be associated with a diuretic, particularly in Ilana’s case where she has lost weight and is possibly deriving blood pressure lowering benefits through self-management behaviour. Her home blood pressure readings and the fact that the symptoms resolve quickly with no other intervention other than a short pause, as well as the fact that the antihyperglycemic agents that Ilana is taking have a low association with hypoglycemia suggest that her symptoms are due to low blood pressure, rather than hypoglycemia. Ilana is taking three agents that can lower blood pressure: Empagliflozin, ramipril and hydrochlorothiazide. Of the three agents listed, ramipril has additional vascular protective effects, while empagliflozin has vascular and renal protective benefits while also supporting blood glucose lowering. As hydrochlorothiazide is not affiliated with these additional benefits, an appropriate therapeutic plan to manage Ilana’s dizzy spells, lightheadedness and frequent urination would be to discontinue hydrochlorothiazide and then reassess Ilana’s symptoms in 2 to 3 weeks. Of note, Ilana should also be checked for the presence of a urinary tract infection (UTI) as a UTI could also result in symptoms of dizziness, lightheadedness and frequent urination. Further to UTIs occurring more frequently in the older adult, UTIs are also a possible adverse effect of the SGLT-2 inhibitor class. [Reference: Chapter 13: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults; Chapter 23: Cardiovascular Protection in People with Diabetes; Chapter 26: Treatment of Hypertension; and Chapter 29: Chronic Kidney Disease in Diabetes]
Reduce/discontinue the ramipril 10mg based on home blood pressure readings and symptoms of dizzy spells and lightheadedness	Incorrect. Ilana is experiencing dizzy spells and lightheadedness. Her home blood pressure readings and the fact that the symptoms resolve quickly with no other intervention other than a short pause, as well as the fact that the antihyperglycemic agents that Ilana is taking have a low association with hypoglycemia suggest that her symptoms are due to low blood pressure, rather than hypoglycemia. Ilana is taking three agents that can lower blood pressure: Empagliflozin, ramipril and hydrochlorothiazide. Because ramipril has additional vascular protective benefits, and because Ilana has CVD (history of MI), in comparison to the other possible agents that contribute to blood pressure lowering, ramipril should not be discontinued at this time. On the other hand, if Ilana (diabetes and ≥ 55 years) did not have hypertension, an additional CV risk factor or end organ damage (albuminuria, retinopathy, left ventricular hypertrophy), the ACE or ARB would not be indicated for vascular protective benefits. Notably, Ilana should also be checked for the presence of a urinary tract infection (UTI) as a UTI could also result in symptoms of dizziness, lightheadedness and frequent urination. Further to UTIs occurring more frequently in the older adult, UTIs are also a possible adverse effect of the SGLT-2 inhibitor class, of which Ilana just started. [Reference: Chapter 13: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults; Chapter 23: Cardiovascular Protection in People with Diabetes; and Chapter 26: Enteric-coated ASA Treatment of Hypertension]
Increase the empagliflozin from 10mg to 25mg once daily as Ilana is not at target A1C and is experiencing polyuria due to hyperglycemia	Incorrect. Although Ilana’s A1C is not at her individualized target (≤ 7.0 %), blood glucose management, with a current A1C of 7.2 %, is of less urgency in a therapeutic plan in comparison to Ilana’s symptoms of dizzy spells and lightheadedness. Once Ilana’s more urgent symptoms are resolved, Ilana’s glycemic control could be reassessed and an increase of pharmacologic glycemic management could be considered in addition to self-management support and revisiting healthy lifestyle choices. [Reference: Chapter 8: Targets for Glycemic Control; Chapter 13: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults; and Chapter 37: Diabetes in Older People]

Reveal Answer

Question 4: Ilana’s husband, Noah, has just started coming to see you. He is 78 years-old and has been living with type 2 diabetes since the age of 55 when he had a MI. His current medications are listed below and his blood work collected 1 week before his appointment with you today are A1C 8.6%, eGFR 42 mL/min/1.73m². BP in your office today 132/83mmHg. Noah walks with a walker and his lovely wife helps him with daily activities.

Metformin 500mg twice daily
Gliclazide MR 60mg once daily
Insulin glargine U-100 55 units s.c. at bedtime
Telmisartan 80mg once daily
Atorvastatin 10mg once daily
Enteric-coated ASA 81mg once daily

Which of the following is TRUE with respect to considerations regarding self-monitoring of blood glucose (SMBG) in the older adult? (More than 1 answer is correct. Can you find them all?)

A.	If there is discrepancy between the A1C value and the home blood glucose monitoring results (based on comparing with a A1C – average blood glucose chart), the A1C value should always take priority in directing glycemic therapy as lab values are generally more accurate
B.	With respect to older people with diabetes, it has been suggested that postprandial glucose values are a better predictor of outcome, rather than A1C or preprandial glucose values
C.	Another benefit of capillary blood glucose monitoring (CBGM) is that CBGM can reveal fluctuations of glucose; and greater variability of glucose values, even with equivalent glycemic control, is associated with worse cognition
D.	Noah’s CBGM targets for someone who is functionally dependent, as per the Diabetes Canada guidelines are, preprandial CBGM 6 to 9mmol/L and postprandial CBGM <14mmol/L

If there is discrepancy between the A1C value and the home blood glucose monitoring results (based on comparing with a A1C – average blood glucose chart), the A1C value should always take priority in directing glycemic therapy as lab values are generally more accurate

Incorrect. Recently, an A1C-derived average blood glucose value has been developed and offered to people with diabetes and health-care providers as a better way to understand glycemic control. While this is a valuable parameter in younger people, this variable and A1C may not accurately reflect measured glucose values or glycemic variability in the older adult. [Reference: Chapter 37: Diabetes in Older People].
Similarly, there are factors that have been identified that affect A1C, see Table 1, Chapter 9: Monitoring Glycemic Control. In particular in the elderly, some of the common factors that can affect A1C are:
Factors that increase A1C: iron deficiency, b12 deficiency, chronic kidney disease, chronic opiate use
Factors that can decrease A1C: Chronic renal failure, Rheumatoid arthritis
[Reference: Chapter 9: Monitoring Glycemic Control]

With respect to older people with diabetes, it has been suggested that postprandial glucose values are a better predictor of outcome, rather than A1C or preprandial glucose values

CORRECT. In fact, older people with type 2 diabetes who have survived an acute myocardial infarct, such as Noah, may have a lower risk for a subsequent CV event with targeting postprandial versus fasting/preprandial glycemia. [Reference: Chapter 37: Diabetes in Older People]

Another benefit of CBGM is that CBGM can reveal fluctuations of glucose; and greater variability of glucose values, even with equivalent glycemic control, is associated with worse cognition

CORRECT. In people with diabetes with equivalent glycemic control, greater variability of glucose values is associated with worse cognition. [Reference: Chapter 37: Diabetes in Older People]

Noah’s CBGM targets for someone who is functionally dependent, as per the Diabetes Canada guidelines are, preprandial CBGM 6 to 9mmol/L and postprandial CBGM <14mmol/L

Incorrect.

CBGM	Functionally independent	Functionally dependent	Frail and/or with dementia	End of life
Preprandial	4 – 7 mmol/L	5 – 8 mmol/L	6 – 9 mmol/L	Individualized
ostprandial	5 – 10 mmol/L	< 12 mmol/L	< 14 mmol/L

[Reference: Chapter 37: Diabetes in Older People]

Reveal Answer

Question 5: Again about Noah: as a reminder, he is 78 years-old and has been living with type 2 diabetes since the age of 55 when he had a MI. His current medications are listed below and his blood work collected 1 week before his appointment with you today are A1C 8.6%, eGFR 42 mL/min/1.73m². BP in your office today 132/83mmHg. Noah walks with a walker and his lovely wife helps him with daily activities.

Metformin 500mg twice daily
Gliclazide MR 60mg once daily
Insulin glargine U-100 55 units s.c. at bedtime
Micardis 80mg once daily
Atorvastatin 10mg once daily
Enteric-coated ASA 81mg once daily

Based on the information we are given about Noah, which of the following is TRUE?

A.	There is no advantage to discontinuing the gliclazide and starting a DPP-4 inhibitor in Noah as neither a sulfonylurea nor a DPP-4 has demonstrated cardiovascular outcome benefit and Noah has CVD (history of a MI).
B.	To further minimize the risk of hypoglycemic events in Noah, glargine U-300 or degludec may be used instead of glargine U-100
C.	Hypoglycemia is actually not a concern for Noah as his A1C is 8.6%, he is not complaining of symptoms, and he likely does not exercise enough to result in low blood glucose
D.	Based on the information provided about Noah, there are NO identifiable risk factors for severe hypoglycemia

There is no advantage to discontinuing the gliclazide and starting a DPP-4 inhibitor in Noah as neither a sulfonylurea nor a DPP-4 has demonstrated cardiovascular outcome benefit and Noah has CVD (history of a MI).	Incorrect. In older people with type 2 diabetes, sulfonylureas should be used with caution because the risk of hypoglycemia increases substantially with age. DPP-4 inhibitors should be used over sulfonylureas as second-line therapy to metformin, because of a lower risk of hypoglycemia. A SGLT-2 inhibitor that has demonstrated CV outcome and renal benefits could be considered for Noah to reduce the risk of major CV events and progression of nephropathy as Noah’s A1C is above his individualized target and he has clinical CV disease. In assessing the appropriateness of a SGLT-2 inhibitor for Noah, consideration should be given to any comorbidities and the complexity thereof. [Reference: Chapter 37: Diabetes in Older People]
To further minimize the risk of hypoglycemic events in Noah, glargine U-300 or degludec may be used instead of glargine U-100	CORRECT. Glargine U-100 is already a better choice over NPH or human 30/70 insulin to lower the frequency of hypoglycemic events. However, to further minimize the risk of hypoglycemic events in Noah, glargine U-300 is associated with a lower frequency of hypoglycemia than glargine U-100 in the older person, and older people appear to have less nocturnal hypoglycemia with insulin degludec than glargine U-100. [Reference: Chapter 37: Diabetes in Older People]
Hypoglycemia is actually not a concern for Noah as his A1C is 8.6%, he is not complaining of symptoms, and he likely does not exercise enough to result in low blood glucose	Incorrect. Asymptomatic hypoglycemia, as assessed by CGM, is frequent in the older adult population. This increased risk of hypoglycemia appears to be due to an age-related reduction in glucagon secretion and impaired awareness of hypoglycemic warning symptoms. Further, although it has been assumed that less stringent A1C targets may minimize the risks of hypoglycemia, it has been demonstrated using CGM that older people with higher A1C levels still have frequent episodes of prolonged asymptomatic hypoglycemia. Note the possible factors that can affect (increase) A1C. Further, hypoglycemia is a concern for Noah because with Noah requiring the use of a walker for daily activities, his altered psychomotor performance may prevent him from taking steps to treat hypoglycemia. [Reference: Chapter 9: Monitoring Glycemic Control; and Chapter 37: Diabetes in Older People]
Based on the information provided about Noah, there are NO identifiable risk factors for severe hypoglycemia	Incorrect. Severe hypoglycemia as by defined in the Diabetes Canada 2018 Clinical Practice Guidelines occurs when an individual requires assistance of another person in managing the hypoglycemic episode. Unconsciousness may occur. Because of this, it is very important to identify who is at risk for severe hypoglycemia, and to take action to minimize the risk of severe hypoglycemia in these individuals. Noah has at least 2 identifiable risk factors for severe hypoglycemia. Which ones are they? Risk factors for severe hypoglycemia in people treated with sulfonylureas or insulin Prior episode of severe hypoglycemia Current low A1C (< 6.0 %) Hypoglycemia unawareness Long duration of insulin therapy Autonomic neuropathy Chronic kidney disease Low economic status, food insecurity Low health literacy Preschool-age children unable to detect and/or treat mild hypoglycemia on their own Adolescence Pregnancy Elderly Cognitive impairment Also of note, the consequences of a moderate-to-severe hypoglycemic episode could include a fall and injury, seizure or coma, or a CV event. [Reference, Chapter 14: Hypoglycemia (Table 3); and Chapter 37: Diabetes in Older People] Note: Noah’s risk factors for severe hypoglycemia: Chronic kidney disease Elderly

Reveal Answer

References for Ilana:

References for Noah:

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