Management of Diabetes in the Elderly. Sylvia Shamanna Internal Medicine (R1)

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1 Management of Diabetes in the Elderly Sylvia Shamanna Internal Medicine (R1)

2 Case 74 year old female with frontal temporal lobe dementia admitted for prolonged delirium and frequent falls (usually in the morning) Type 2 DM: currently treated with metformin 500 BID and insulin novolin 30/70 (33U before breakfast and 22U with dinner) Most recent hemoglobin A1c = 6.5% Significant behavioral issues, including refusal of medications Social hx: Living in DAL Staff in charge of administering medications

3 Outline Diabetes complications Hyperglycemia Hypoglycemia Glycemic targets Management

4 Issues Diabetes Complications Elderly patients with DM have same risk developing of macrovascular and microvascular complications as the general population Absolute risk of of CV disease in elderly patients much higher than that of their younger counterparts

5 Hyperglycemia Increase in A1c by 1% is associated with: 18% increase in risk of cardiovascular events 12-14% increase in the risk of death 37% increase in the risk of retinopathy or renal failure

6 Hyperglycemia Hyperglycemia: Can increase dehydration Worsens vision Worsens cognition? elderly able to tolerate higher levels of hyperglycemia before becoming symptomatic due to decreased GFR

7 Hypoglycemia Hypoglycemia: Also worsens cognition and function More neuroglycopenic manifestations (dizziness, weakness, delirium, confusion) in the elderly Increases risk of falls Associated with development of dementia

8 Hypoglycemia and dementia Whitmer et al (2009): Severe episodes of hypoglycemia, requiring visit to ER, increases risk of developing dementia (linear relationship) Patients most likely to develop hypoglycemia: Older age African American Treated with insulin Co-morbidities: HTN, stroke, end-stage renal disease

9 poglycemia and dementia was not limited to these factors. Results for patients with ED events only were similar to the results for patients with any events. Compared with patients with no ED-derived hypoglycemic episodes, as determined from outpatient records, patients with 1 hypoglycemic episode resulting in an ED visit had an HR of 1.42 (95% CI, ), and those with 2 or more episodes had an HR of 2.36 (95% CI, ). To determine whether a hypoglycemia diagnosis from the ED may have been simply incidental, we examined the average total number of diagto evaluate whether severe episodes of hypoglycemia are associated with subsequent risk of dementia in older patients with type 2 diabetes. Our re- Relationship between hypoglycemia and sults suggest that hypoglycemic episodes severe enough to require hospitalization or an ED visit are associated dementia in with type 2 DM with increased risk of dementia, particularly for patients who have a history of multiple episodes. Specifically, we observed a 2.39% increase in absolute risk of dementia per year of follow-up for patients with history of hypoglycemia, compared with patients without a history. Although this 1-year absolute risk difference is modest, the quelae including neuronal cell death, which may accelerate the process of dementia. 6 Hypoglycemia also increases platelet aggregation and fibrinogen formation, 37 and this may accelerate vascular compromise in the brain. Animal studies have illustrated that hypoglycemic coma causes damage to neuronal receptors in the ca-1, subiculum dentate, and granule cell areas of the hippocampus, regions critical for learning and memory. 16 Repeated episodes of hypoglycemia could affect cognition through damage to these regions, particularly in brains that may be vulnerable due to old age. Table 2. Frequency of Hypoglycemic Episodes by Dementia Status Dementia (n = 1822) No. (%) Nondementia (n = ) Age-Adjusted Incidence Rates per Person-Years (95% CI) Any hypoglycemia No 1572 (10.34) (89.66) ( ) Excess Attributable Risk per Year, % (95% CI) a Yes 250 (16.95) 1215 (83.05) b ( ) 2.39 ( ) No. of hypoglycemic episodes (10.34) (89.66) ( ) (14.84) 852 (85.16) ( ) 1.64 ( ) 2 57 (22.26) 201 (77.74) ( ) 4.34 ( ) 3 or more 43 (20.40) 162 (79.60) b ( ) 4.28 ( ) Abbreviation: CI, confidence interval. a Attributable risk calculated as difference between rate in group and rate in reference group (0 hypoglycemic events). b P values were less than.001 and were calculated using the 2 test. Table 3. Hypoglycemia and Risk of Incident Dementia a Hazard Ratio (95% Confidence Interval) No. of Hypoglycemic Episodes b No. of Dementia Cases Adjusted for Age (as Time Scale), BMI, Race/Ethnicity, Education, Sex, and Duration of Diabetes Additionally Adjusted for Comorbidities c Additionally Adjusted for 7-Year Mean HbA 1c Level, Diabetes Treatment, and Years of Insulin Use 1 or more ( ) 1.48 ( ) 1.44 ( )

10 Relationship between A1c and Hypoglycemia Data from The Diabetes Control and Complications Trial Research Group, N Engl J Med 1993; 329:977.

11 Geriatric Specific Issues Geriatric specific issues: Falls Polypharmacy & Medication management Meal preparation Exercise tolerance

12 Falls & Diabetes Schwartz et al: Intensive treatment (A1c 6%) with insulin increases the risk of falls. Intensive treatment with OHG alone does not increase risk Diabetes complications (incl. peripheral neuropathy, retinopathy and decreased renal function) also contribute to risk of falls

13 Glycemic Targets Healthy elderly patients with life expectancy >10 years: Hemoglobin A1c <7% Patients at high risk of cardiovascular disease: A1c =7-7.9% No specific guidelines for those with life expectancy <10 years and multiple co-morbidities Treatment goal: prevent hypoglycemia while avoiding symptoms of hyperglycemia

14 Management Non-Pharmacologic: Referral to interdisciplinary diabetes healthcare team Nutritional education Physical exercise

15 Management Oral hypoglycemics: Metformin (first line) low risk of hypoglycemia risk of lactic acidosis (only use of GFR >30 ml/min) side effects: weight loss and GI upset Sulfonylureas: Use with extreme caution because risk of hypglycemia increases with age Short acting (gliclazide and glimepiride) have lower incidents of hypoglycemia and CV events in the elderly

16 Management Thiazolidinediones: Not associated with hypoglycemia Use with caution in patients with cardiovascular disease as increased incidence of CHF and edema Meglitinides: Lower incidence of hypoglycemia compared to glyburide Preferred in individuals with irregular eating habits Alpha-glucosidase inhibitors: May be used alone or in combination with insulin, a sulfonylurea and metformin Safe and modestly effective Many cannot tolerate due to GI side effects (diarrhea and flatulence)

17 Management DDP - IV inhibitors: No risk of hypoglycemia and weight neutral Expensive No data on long-term safety or use in the elderly GPL -1 therapies: No risk of hypoglycemia Associated with weight loss Nausea, vomiting and diarrhea common Post-marketing reports of acute pancreatitis and worsening of renal function

18 Management Insulin: Need to evaluate if patient is capable of calculating dose of insulin, administering insulin, monitoring blood glucose and treating hypoglycemia prior to initiating treatment May require additional help from family, caregivers or home care Use of pre-mixed insulin and pre-filled pens decreases medication errors Need to re-evaluate insulin regime as level of care changes

19 Back to the case... Date AM BG Lunch BG August 9 August 10 August 11 August 12 August 13 Supper BG Bedtime BG Therapy/Notes 33U Insulin 22U Insulin supper Patient denied symptoms of hypoglycemia. Refused apple juice initially. Repeat BG 2h later = 10.8, thus given 33U Insulin before lunch Decreased Insulin to 18 U at supper 33U Insulin Decreased to 16U Insulin supper 33U Insulin 16U breakfast 33U Insulin 16U Insulin supper **NB Patient was also receiving Metformin 500 mg BID daily

20 Case Conclusions: Long-term management goals: Avoid morning hypoglycemia Will have to tolerate hyperglycemia as long as patient is not symptomatic Target A1c? Will need to re-evaluate management as dementia progresses

21 References Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358:2545. Canadian Diabetes Association Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada Vol 32, Section 1. McCulloch, D., Munshi, M. Treatment of tyle 2 diabetes mellitus in the elderly patient. (August 2011) Schwartz AV, Vittinghoff E, Sellmeyer DE, et al. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care 2008; 31:391. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329:977. Whitmer RA, Karter AJ, Yaffe K, et al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 2009; 301:1565.

22 Questions?

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