5/16/2018 COGNITIVE HEALTH AND DIABETES WORKSHOP I HAVE NO FINANCIAL CONFLICTS OF INTEREST

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1 COGNITIVE HEALTH AND DIABETES WORKSHOP HEATHER FERRIS, MD, PHD ASSISTANT PROFESSOR, DIVISION OF ENDOCRINOLOGY AND METABOLISM CLINICAL INVESTIGATOR IN RESIDENCE, DEPARTMENT OF NEUROSCIENCE I HAVE NO FINANCIAL CONFLICTS OF INTEREST Disclaimer: You will be hearing a lot of opinion today, mine and others. There aren t a lot of data or guidelines

2 Objectives Make rational decisions on glycemic targets. Make adjustments to medication regimens to reduce the risk of hypoglycemia. Understand risks of frequently used medications to brain health. Describe non pharmacologic interventions to improve brain health in our patients. Outline Healthy aging versus pathologic aging Special considerations in the elderly population Guidelines for diabetes and CVD Aging Healthy Minimal cognitive decline Do not require assistance with ADL s Few if any diseases of aging Pathologic Significant cognitive impairment Dependent on others for ADL s Multiple comorbidities, often life limiting. 6 2

3 Aging Healthy Minimal cognitive decline Does not require assistance with ADL s Few if any diseases of aging Pathologic Significant cognitive impairment Dependent on others for ADL s Multiple comorbidities, often lifelimiting. 7 Frailty Phenotype Weakness Slowness Low level of physical activity Self reported exhaustion Weight loss Frailty Categories Mild Needs help with housekeeping Moderate Needs help with ADL s Life expectancy with diabetes is 23 months Severe Nursing home patients 3

4 CASE 1 78 yo female with hx of Type 2 diabetes (20 years), esophageal stricture, hypothyroidism and depression. Sent by PCP because most recent HgbA1c was 9.5% on sitagliptan 100mg daily detemir insulin 75units BID She checks her sugars once a day Allergy to metformin (nausea and vomiting) but thinks she took it for many years before it was stopped 10 CASE 1 She complains of dizziness and frequent falls Dizziness limits her ability to exercise She has pain and lumps at her insulin injection sites Other meds include: Asa 81mg daily Duloxetine 60mg daily Hydrochlorothiazide 12.5mg daily Metoprolol XL 25mg daily Levothyroxine 75 mcg daily Omeprazole 40mg daily 11 CASE 1 Accompanied by a niece who has recently taken over the food shopping and worries about her aunt s ability to manage her diabetes medications Frail, elderly woman. Very hard of hearing. BMI 33 BP 90/50, P 97 Lipohypertrophy at insulin injection sites but otherwise unremarkable exam egfr

5 CASE 1 What should we do next? 13 Special Considerations in the Elderly Population There is a greater degree of beta cell failure For a given BMI there is generally less lean mass It is very important that exercise is part of weight loss in the elderly or they will have significant loss of lean mass A1c is less representative of glycemic control with age and increased comorbidities Risks of Hyperglycemia Glucosuria results in dehydration/aki, orthostasis/falls All cause, CV and cancer mortality seems to increase in adults with A1c s >8.0% Age >74 years, no clear association between A1c and all cause mortality Palta, Diabetes Care

6 METFORMIN egfr Above 4 mg/l is considered elevated. Lalau, Diabetes Care METFORMIN AND COGNITION As many studies showing that metformin improves cognition as those that show it worsens it Metformin can cause B12 deficiency which can impair cognition MVI vs. B12 supplement vs. periodic screening for B12 deficiency? 17 CASE 1 Stop hydrochlorothiazide Start metformin ER 500 mg daily Split insulin dose into 3 injections (50 TID) for better comfort/absorption Check blood sugar 3x per day 18 6

7 CASE 1 2 weeks later she reports am BG of s, afternoon , a 3am of 70 Add a second metformin and reduce evening insulin to 30 units 2 weeks later she is having midday lows and fasting BG of Decrease detemir to 50 units BID. Follow up A1c was 8% 19 CASE 2 74yo patient with 55 years of type 1 diabetes She has been using insulin pump therapy for the past 10+ years successfully with an average A1c of 7 7.5%. Recently her A1c has drifted up over 8%. She brings in her glucose logs and they are filled out, but with many more extraneous details than in the past. She can recite to you her pump settings but can t explain to you how she would trouble shoot a high blood sugar. 20 CASE 2 How would you manage this patient? 21 7

8 CASE 2 She seems to be experiencing an impairment of her executive function. 1. CGM 2. Hybrid closed loop system (not covered by Medicare) 3. Enlist a family member to assist more in management 4. More frequent visits 5. When do you stop pump therapy? 22 CASE 2 What if frequent hypoglycemia was the problem? Is it her cognition, worsening hypoglycemia unawareness or behaviors that were rewarded when she was younger? 1. CGM with alarms, have it shared with a family member 2. Counseling about less stringent BG goals at every visit 3. Stop pump therapy 23 Response to hypoglycemia in aging Increased hypoglycemia unawareness Impaired catecholamine response due to age Frequent use of beta blockers and other medications which impair hypoglycemia awareness Decreased cognitive reserve Your blood sugar should be above your age 8

9 Hypoglycemia symptoms in normal males varies with age Age Age Matyka, Diabetes Care Hypoglycemia symptoms in normal males varies with age (54) (50) (50) (64) (62) (50) (54) (46) (50) (50) (54) (50) Matyka, Diabetes Care CASE 2 WISDM Trial Type 1 DM over age 60 Randomized to CGM or free meter/strips and blinded CGM at 3 time points during the 6 mo study Primary outcome hypoglycemia reduction 27 9

10 CASE 3 70 yo with 20+ years of Type 2 diabetes, A1c 10% He recently retired and is having trouble affording his medications He cannot tell me what most of his medications are for or explain how he decides on his mealtime insulin dose He is having lows weekly Metformin 1000mg BID Glargine U units daily Aspart units with each meal Empagliflozin 10mg 28 What next? CASE 3 29 SIMPLIFICATION STUDY Single center study of 65 patients >65 yo On 2 or more insulin injections per day 1 or more glucoses on CGM <70 over 5 days Stimulated C peptide >1.1 ng/ml Transitioned to am glargine and non insulin agents as needed over a 5 month period, followed by 5 day CGM No study contact for 3 mo, then follow up and final CGM Munshi, JAMA Int Med,

11 SIMPLIFICATION STUDY Munshi, JAMA Int Med, SIMPLIFICATION STUDY Increase in A1c for those <7% of +0.37% HbA1c 8.1 9% Decrease of 0.5% >9% Decrease of 1.7% No change for 7.1 8% Amount of time in hypoglycemia did not correlate with HbA1c, only with treatment regimen Munshi, JAMA Int Med, Beers Criteria List of medications to avoid in elderly patients GLYBURIDE SLIDING SCALE INSULIN Amitriptyline 11

12 CASE 3 Switch to glargine vial 20 units QAM Stop all mealtime insulin With discontinuation of mealtime insulin he can now afford empagliflozin prescription 3mo follow up A1c 9.3%, no lows Increase glargine to 22 units Nutrition counseling 34 CASE 3 Glipizide or glimepiride after checking a c peptide Pioglitizone 35 CASE 3 What is you can t stop mealtime insulin? Fixed dose Would a smart pen help? NovoPen Echo memory and half unit dosing Timesulin Insulin cap time since last injection Gocap, InPen, Esysta records dose, time and insulin type, sends to smartphone 36 12

13 CASE 4 You see a 45yo patient with prediabetes and a family history of Alzheimer s disease. He is concerned about his brain health. How do you advise him? 37 3 Year Observational Study of High versus Low Mediterranean Diet Amyloid Glucose Uptake Berti, Neurology PrediMed Cognitive Function Subcohort Approximately 150 patients per group randomized to low fat diet, Mediterranean + olive oil or Mediterranean + nuts Cognitive testing at the baseline and 4 years 13

14 PrediMed Cognitive Function Subcohort Valls Pedret, JAMA Int Med 2015 PrediMed Cognitive Function Subcohort Estruch, NEJM 2013 CASE 5 74 yo male with hx of Type 2 diabetes, neuropathy and PVD s/p R. SFA/popliteal artery stent and CAD s/p LAD stent HgbA1c 4 months earlier was 7.2% on Metformin 500 mg BID Pioglitizone 30mg Liraglutide 1.8 mcg Glargine u QAM 42 14

15 CASE 5 The month before we met he had a witnessed VTach arrest, received CPR EF reduced to 25 30% BiV ICD placed and then discharged home on increased beta blocker and amiodarone Pioglitazone and metformin were stopped. 4 days later went into V tach storm, ICD fired, hospitalized for several more days. Amiodarone and beta blocker increased further. 43 CASE 5 2 weeks later comes to endocrine clinic taking Liraglutide 0.6 mcg daily, glargine 7 13 units daily Weight is down about 15 pounds, poor appetite Will be starting cardiac rehab soon BG getting down to about 70 every other day since discharge He confides that he is having memory problems since the rescusitation 44 My goal: NO HYPOGLYCEMIA!! CASE 5 Memory issues Poor appetite Huge doses of beta blockers About to restart exercise 45 15

16 What next? CASE 5 Stopped insulin Titrated up liraglutide Started cardiac rehab Goal A1c 7.5% 46 Hypoglycemia in the Elderly Population Hospitalization for hypoglycemia exceeds hospitalization for hyperglycemia in the elderly Having 2 or more comorbidities increased risk of severe hypo by >50% (1) CAD/MI CHF Lung disease CKD Depression Dementia Stroke Afib Lipska et al. Diabetes Care Patients With Events (%) CV death, nonfatal MI, & 25 stroke 20 HR 0.90 ( ) 15 P= Standard therapy 5 Intensive therapy Time (Years) ACCORD Patients With Events (%) % mortality Intensive therapy Standard therapy Time (Years) ACCORD Study Group, NEJM

17 ARRHYTHMIAS 25 patients with Type 2 diabetes and CAD or at least 2 risk factors, on insulin 5 day 12 lead Holter monitor and CGM Nocturnal hypoglycemia associated with prolonged QTc, abnormal t waves, bradycardia, ectopic atrial and ventricular beats Chow, Diabetes CVD Risk Factor Management AHA <130/80 AHA <130/80 Korytkowski, Diabetes Care CASE 5 The nausea from amiodarone dissipated and weight started to come back. Metformin 500 mg BID added back Empagliflozin 10 mg started (replacing pio) Eventually added back units of glargine Peak A1c 8.5%, no hypoglycemia 51 17

18 TAKE HOME MESSAGES The elderly are more at risk of developing neuroglycopenia. Those with cognitive impairment are at greater risk for hypoglycemia. Often simplification of the regimen can result in better control with fewer lows. Technology may be helpful in some patients with mild cognitive impairment but must be individualized