1 / 39

Donuts, Diabetes and Decisions: Optimizing Diabetes Care to Maximize Brain Health

Donuts, Diabetes and Decisions: Optimizing Diabetes Care to Maximize Brain Health. Aida wen, md Associate professor Department of geriatric medicine jabsom. 2/14/18. Objectives. Understand how hyperglycemia can cause cognitive decline

marilyn
Download Presentation

Donuts, Diabetes and Decisions: Optimizing Diabetes Care to Maximize Brain Health

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Donuts, Diabetes and Decisions: Optimizing Diabetes Care to Maximize Brain Health Aida wen, md Associate professor Department of geriatric medicine jabsom 2/14/18

  2. Objectives • Understand how hyperglycemia can cause cognitive decline • Understand how hypoglycemia can worsen cognitive decline • Be able to develop a target HbA1c treatment strategy for elderly patients. • Be able to utilize the eprognosis website as a resource to discuss goals of care for diabetes patients.

  3. Prevalence of Diabetes in the Elderly Non-Institutionalized Population by Age (1980–2014) • By 2050 ⟹ Prevalence will increase to 1 in 3 Americans • By 2030 ⟹ Prevalence will double https://www.cdc.gov/diabetes/statistics/prev/national/figbyage.htm

  4. Diabetes Cardiovascular Disease There is a strong correlation between Diabetes and cardiovascular disease (CVD).

  5. But it appears that Diabetes D’oh! …is ALSO related to Dementia!

  6. Diabetes  Cognitive Decline HYPERGLYCEMIA Macrovascular disease Microvascular disease Stroke Vascular dementia ABOUT 2X RISK Arch Intern Med. 2004 Jul 12; 164(13):1422-6. ABOUT 2-3X RISK Diabetes Care. 2016 Feb; 39(2): 300–307

  7. Diabetes  Cognitive Decline DIABETES Macrovascular disease Neurodegenerative disease Microvascular disease Non-vascular dementia Vascular dementia Stroke ABOUT 2X RISK Arch Intern Med. 2004 Jul 12; 164(13):1422-6. ABOUT 2-3X RISK Diabetes Care. 2016 Feb; 39(2): 300–307 ABOUT 2X RISK Lancet Neurol. 2006 Jan; 5(1):64-74.

  8. 2574 Japanese-American Men • Dx: DM, Cognitive exam, MRI, autopsy, genetic testing APOE Ɛ4 allele. • Logistic regression to assess the RR of developing dementia Adjusted RR for dementia of type 2 diabetes (ADA definition) • Peila R et al. Diabetes, Vol 51, April 2002, p. 1256-1262

  9. Pathophysiology: Brain Insulin BBB BRAIN INSULIN PERIPHERAL INSULIN Modulates neurotransmitters (synapse formation) Neurotropic/ Neuroprotective Antioxidative and anti-ischemic Helps body absorb glucose Blazquez E et al. Insulin in the Brain: Its Pathophysiological Implications for States Related with Central Insulin Resistance, Type 2 Diabetes and Alzheimer’s Disease. Frontiers in Endocrinology 2014;5:161 Blazquez E et al. Insulin in the Brain: Its Pathophysiological Implications for States Related with Central Insulin Resistance, Type 2 Diabetes and Alzheimer’s Disease. Frontiers in Endocrinology 2014;5:161

  10. AKA: TYPE 3 DIABETES Pathophysiology: Brain Insulin and T2DM BBB HIGH Glucose Inflammation BRAIN INSULIN PERIPHERAL INSULIN HIGH GlucoseInflammation Aβ formation Plaques  Formation of new synapses Neurotropic/ Neuroprotective Antioxidative and anti-ischemic INSULIN RESISTANCE Helps body absorb glucose INSULIN RESISTANCE Blazquez E et al. Insulin in the Brain: Its Pathophysiological Implications for States Related with Central Insulin Resistance, Type 2 Diabetes and Alzheimer’s Disease. Frontiers in Endocrinology 2014;5:161

  11. Diabetes increases Plaque formation Hyperglycemia increases inflammation, impairs insulin signaling, and exacerbates the production of Aβ, which increases Plaques and causes cell death HYPERGLYCEMIA Catrina Sims-Robinson et al; How does diabetes accelerate Alzheimer disease pathology? Nat Rev Neurol. 2010 Oct; 6(10):551-55

  12. Prevention? Oh, Doc! I don’t want Homer’s heart OR brain to fail…

  13. DM Control Reduces Risk of Macrovascular Complications • The Diabetes Control and Complications Trial (DCCT) • Performed in T1D patients randomized 1141 patients to either • Intensive Control (achieving HbA1c of 7.4%) vs. conventional therapy (HbA1c of 9.1%) • In long term follow-up (mean of 17 years), early intensive glucose control resulted in a significant 57% reduction in the combination of nonfatal MI, stroke or cardiovascular death (p=0.02) Nathan DM, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353 (25):2643–53.

  14. DM Control Reduces Risk of Microvascular Disease • UKPDS 34 • The study concluded that compared to intensive sulfonylureas or insulin control, intensive therapy with metformin (target FBG ≤ 6 mmol/L), • Significantly greater risk reduction of developing any diabetes-related endpoint: • Death due to macrovascular (MI and stroke) • Microvascular complications, such as retinopathy, (P=0·0034), • All-cause mortality (P=0·021), • Stroke (P=0·032). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854–65.

  15. Effect of the treatment of Type 2 diabetes mellitus on the development of Cognitive Impairment and Dementia.2017 • MAIN RESULTS: • We identified seven eligible studies but only four provided data we could include in efficacy analyses. Two of these studies compared intensive versus standard glycemic control and two compared different pharmacological treatments. All studies were at unclear risk of bias in at least two domains and one large study was at high risk of performance and detection bias. • AUTHORS' CONCLUSIONS: • We found no good evidence that any specific treatment or treatment strategy for Type 2 diabetes can prevent or delay cognitive impairment. The best available evidence related to the comparison of intensive with standard glycaemic control strategies. Here there was moderate-quality evidence that the strategies do not differ in their effect on global cognitive functioning over 40 to 60 months (4-5 years) Studies included: Zimering 2016, Ryan 2006, Launer 2011, Araki 2012, ADVANCE 2008, Abbetecola 2006 AreosaSastre et al. Cocharane Database Systematic Review. 2017 Jun 15;6:CD003804. doi: 10.1002/14651858.CD003804.pub2. [Epub ahead of print]

  16. Homer wanted to please Marge, so he tried hard …. ….however

  17. Hypoglycemia Falls Arrythmias Acute Severe Hypoglycemia Hospitalizations (due to ADE) Brain damage MAURER ET ALJournal of Gerontology:2005, Vol. 60A, No. 9, 1157–1162

  18. Glucose Level & Arrhythmia Hypoglycemia IG <3.5 mmol (<70MG/Dl) Hyperglycemia IG >15 mmol/L (>250MG/DL) Continuous Glucose Monitoring & Holter Monitor Chow etal Diabetes 2014;63:1738–1747 | DOI: 10.2337/db13-0468

  19. Hypoglycemia Neuronal damage Acute Severe Hypoglycemia Cognitive Decline DEMENTIA

  20. Association of Hypoglycemia With Subsequent Dementia in Older Patients With Type 2 Diabetes Mellitus. METHODS RESULTS 5.7% (n = 3,018) had at least one hypoglycemia episodes. The overall incidence rate of dementia = 12.7 per 1,000 person-years. The occurrence of at least one hypoglycemia episode was associated with higher odds of subsequent dementia one episode (HR= 1.26; 95% CI = 1.03-1.54); two or more episodes (HR = 1.50; 95% CI = 1.09-2.08). • Retrospective longitudinal cohort study (2003 to 2012). • Patients aged >65 years diagnosed with type 2 diabetes, with no prior diagnosis of dementia. • All patients were followed from the date of initial diabetes diagnosis. N= 53,055 Mehta HB, Mehta V, Goodwin JS. Association of Hypoglycemia With Subsequent Dementia in Older Patients With Type 2 Diabetes Mellitus. J Gerontol A BiolSci Med Sci. 2016 Oct 26. pii: glw217.

  21. Hypoglycemia Dementia Meta-analysis of five studies showed a significantly increased risk of dementia in patients who had hypoglycemic episodes: pooled odds ratio 1.68 [95% CI 1.45, 1.95]. Meta-analysis of five studies showed a significantly increased risk of hypoglycemia in patients with dementia: pooled odds ratio 1.61 (95% CI 1.25, 2.06). Neuronal damage Acute Severe Hypoglycemia Cognitive Decline DEMENTIA Mattishent K, Loke YK. Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis. Diabetes ObesMetab. 2016 Feb;18(2):135-41.

  22. Treatment Strategies OK, Doc. So tell me what should I do…

  23. Considerations • Consider Risks • Consider comorbidities • Consider Prognosis • Consider support system

  24. Consider Lag-time to benefit for Preventive Care • For frail elders with shorter life expectancy, in the short term (e.g. 6 y) , the risks of hypoglycemia are greater than the benefits of tight glucose control • For robust elders with recent diagnosis, in tighter glucose control yields longer term benefits (e.g. 10- 20 y), …but does not guarantee against dementia Eprognosis.com

  25. http://eprognosis.ucsf.edu/index.php

  26. Eprognosis determines an appropriate prediction algorithm • Based on Setting • Demographics • Age

  27. Homer Simpson, 66 year old Male, with HTN, DM, CHF

  28. What is the Target A1c? Kirkman et l-2012-Journal of the American Geriatrics Society

  29. AGS Guideline For A1c EXPERT PANEL ON THE CARE OF OLDER ADULTS WITH DIABETES MELLITUS NOVEMBER 2013–VOL. 61, NO. 11 JAGS

  30. What HbA1c target would you recommend for Homer? • 6.5 • 7.0 • 7.5 • 8.0 • 8.5

  31. Medication Strategies that Minimize Hypoglycemia PREFER AVOID Sulfonylureas (glipizide safest) Sliding scale insulin • Metformin (beware if GFR<30) • Thiazolidiones (TZD)- beware CHF • Actos, Avandia • DPP4 Inhibitors- beware CHF • Sitagliptin (Januvia) • Linagliptin (Tradjenta)

  32. It never hurts to encourage diet and exercise! Which improves FUNCTION and Quality of Life!

  33. What if you saw Homer at 76 years old? Now what is your target Hb A1c? And now he has some IADL difficulty (household chores & handling money? 6.5 7.0 7.5 8.0 8.5

  34. What is the Target A1c? Kirkman et l-2012-Journal of the American Geriatrics Society

  35. Summary (1) • Diabetes is a major risk factor for Dementia: Screen ALL older DM patients for Dementia • Long-term tight control (> 17 years) reduces the incidence of Strokes and Vascular dementia • (as well as heart, kidney, nerves, eye complications) • Short-term treatment of DM (<6 years) does not impact the development of dementia

  36. Summary (2) • There is also a higher rate of Alzheimer’s Disease related to insulin resistance and APOE Ɛ4 • Avoidance of Hypoglycemia is important to minimize the risk of cognitive decline • Dementia impacts the management of Diabetes Provide support • Adjust HbA1c targets

  37. Remember The Ultimate Goal: Quality of Life

  38. Cases or Questions?

More Related