Donuts Diabetes and Decisions Optimizing Diabetes Care to
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 1. Understand how hyperglycemia can cause cognitive decline 2. Understand how hypoglycemia can worsen cognitive decline 3. Be able to develop a target Hb. A 1 c treatment strategy for elderly patients. 4. Be able to utilize the eprognosis website as a resource to discuss goals of care for diabetes patients.
Prevalence of Diabetes in the Elderly Non-Institutionalized Population by Age (1980– 2014) By 2030 � Prevalence will double By 2050 � Prevalence will increase to 1 in 3 Americans https: //www. cdc. gov/diabetes/statistics/prev/national/figbyage. htm
Diabetes Cardiovascular Disease There is a strong correlation between Diabetes and cardiovascular disease (CVD).
But it appears that Diabetes D’oh! …is ALSO related to Dementia!
Diabetes Cognitive Decline HYPERGLYCEMIA Macrovascular disease Microvascular disease Stroke Vascular dementia ABOUT 2 X RISK Arch Intern Med. 2004 Jul 12; 164(13): 1422 -6. ABOUT 2 -3 X RISK Diabetes Care. 2016 Feb; 39(2): 300– 307
Diabetes Cognitive Decline DIABETES Macrovascular disease Stroke ABOUT 2 X RISK Arch Intern Med. 2004 Jul 12; 164(13): 1422 -6. Microvascular disease Vascular dementia ABOUT 2 -3 X RISK Diabetes Care. 2016 Feb; 39(2): 300– 307 Neurodegenerative disease Non-vascular dementia ABOUT 2 X RISK Lancet Neurol. 2006 Jan; 5(1): 64 -74.
Adjusted RR for dementia of type 2 diabetes (ADA definition) 2574 Japanese-American Men DEMENTIA TYPE RR (95% CI) for Dementia Dx: DM, Cognitive exam, MRI, autopsy, genetic testing APOE Ɛ 4 allele. Total Dementia 1. 6 (1. 1 -2. 4) Vascular Dementia 2. 9 (1. 2 -6. 5) Alzheimer’s Disease 1. 9 (1. 1 -3. 2) AD without CVD 1. 8 (0. 9 - 3. 5) Logistic regression to assess the RR of developing dementia Peila R et al. Diabetes, Vol 51, April 2002, p. 1256 -1262
Pathophysiology: Brain Insulin BRAIN INSULIN PERIPHERAL INSULIN B B B Helps body absorb glucose Modulates Neurotropic/ Neuroprotective neurotransmitters Antioxidative and anti-ischemic (synapse formation) Blazquez EE et et al. Insulin in in the Brain: Its Pathophysiological Implications for States Related with Central Insulin Resistance, Type 22 Diabetes and Alzheimer’s Disease. Frontiers in in Endocrinology 2014; 5: 161
AKA: TYPE 3 DIABETES o luc se HG HIG luco HG HIG Pathophysiology: Brain Insulin and T 2 DM n Helps body absorb glucose LIN U S N I CE N A T S RESI n o i t a m r fo ues β A Plaq Formation of Neurotropic/ Neuroprotective N I new synapses UL Antioxidative and anti-ischemic INS NCE tio ma am B BRAIN INSULIN n atio l Inf m am Infl se PERIPHERAL INSULIN A IST S E R 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
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
Prevention? Oh, Doc! I don’t want Homer’s heart OR brain to fail…
DM Control Reduces Risk of Macrovascular Complications The Diabetes Control and Complications Trial (DCCT) §Performed in T 1 D patients randomized 1141 patients to either §Intensive Control (achieving Hb. A 1 c of 7. 4%) vs. conventional therapy (Hb. A 1 c 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.
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.
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 Areosa Sastre et al. Cocharane Database Systematic Review. 2017 Jun 15; 6: CD 003804. doi: 10. 1002/14651858. CD 003804. pub 2.
Homer wanted to please Marge, so he tried hard …. however
Hypoglycemia Falls Acute Severe Hypoglycemia Arrythmias Hospitalizations (due to ADE) Brain damage MAURER ET ALJournal of Gerontology: 2005, Vol. 60 A, No. 9, 1157– 1162
Glucose Level & Arrhythmia HYPOGLYCEMIA HYPERGLYCEMIA IG <3. 5 MMOL (<70 MG/DL) IG >15 MMOL/L (>250 MG/DL) Day Night ↑ VPB Transient ↑ HR Bradycardia ↑ Atrial ectopic ↑ VPB Prolong QTc ↑ VPB No arrhythmia Prolonged QTc Continuous Glucose Monitoring & Holter Monitor Chow et al Diabetes 2014; 63: 1738– 1747 | DOI: 10. 2337/db 13 -0468
Hypoglycemia Acute Severe Hypoglycemia Neuronal damage Cognitive Decline DEMENTIA
Association of Hypoglycemia With Subsequent Dementia in Older Patients With Type 2 Diabetes Mellitus. METHODS v Retrospective longitudinal cohort study (2003 to 2012). v. Patients aged >65 years diagnosed with type 2 diabetes, with no prior diagnosis of dementia. v. All patients were followed from the date of initial diabetes diagnosis. N= 53, 055 RESULTS v 5. 7% (n = 3, 018) had at least one hypoglycemia episodes. v. The overall incidence rate of dementia = 12. 7 per 1, 000 person-years. v. The occurrence of at least one hypoglycemia episode was associated with higher odds of subsequent dementia vone episode (HR= 1. 26; 95% CI = 1. 03 -1. 54); vtwo or more episodes (HR = 1. 50; 95% CI = 1. 09 -2. 08). Mehta HB, Mehta V, Goodwin JS. Association of Hypoglycemia With Subsequent Dementia in Older Patients With Type 2 Diabetes Mellitus. J Gerontol A Biol Sci Med Sci. 2016 Oct 26. pii: glw 217.
Hypoglycemia 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). Dementia Acute Severe Hypoglycemia Neuronal damage DEMENTIA Cognitive Decline 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]. 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 Obes Metab. 2016 Feb; 18(2): 135 -41.
Treatment Strategies OK, Doc. So tell me what should I do…
Considerations Consider Risks Consider comorbidities Consider Prognosis Consider support system
Consider Lag-time to benefit for Preventive Care 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 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
http: //eprognosis. ucsf. edu/index. php
Eprognosis determines an appropriate prediction algorithm q. Based on Setting q. Demographics q. Age
Homer Simpson, 66 year old Male, with HTN, DM, CHF
What is the Target A 1 c? Kirkman et l-2012 -Journal of the American Geriatrics Society
AGS Guideline For A 1 c Patient characteristics Resonable Goal A 1 c Older adult in general 7. 5 -8% Healthy older adults with few comorbidities and 7 -7. 5 % good functional status Older adults with multiple comorbidities, poor health, and limited life expectancy 8 -9 % There is potential harm in lowering Hb. A 1 c to less than 6. 5% in older adults with type 2 DM EXPERT PANEL ON THE CARE OF OLDER ADULTS WITH DIABETES MELLITUS NOVEMBER 2013–VOL. 61, NO. 11 JAGS
What Hb. A 1 c target would you recommend for Homer? A. 6. 5 B. 7. 0 C. 7. 5 D. 8. 0 E. 8. 5
Medication Strategies that Minimize Hypoglycemia PREFER AVOID Metformin (beware if GFR<30) Sulfonylureas (glipizide safest) Thiazolidiones (TZD)- beware CHF Sliding scale insulin ◦ Actos, Avandia DPP 4 Inhibitors- beware CHF o. Sitagliptin (Januvia) o. Linagliptin (Tradjenta)
It never hurts to encourage diet and exercise! Which improves FUNCTION and Quality of Life!
Now what is your target Hb A 1 c? A. 6. 5 B. 7. 0 C. 7. 5 D. 8. 0 E. 8. 5 What if you saw Homer at 76 years old? AND NOW HE HAS SOME IADL DIFFICULTY (HOUSEHOLD CHORES & HANDLING MONEY?
What is the Target A 1 c? Kirkman et l-2012 -Journal of the American Geriatrics Society
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
Summary (2) There is also a higher rate of Alzheimer’s Disease related to insulin resistance and APOE Ɛ 4 Avoidance of Hypoglycemia is important to minimize the risk of cognitive decline Dementia impacts the management of Diabetes Provide support Adjust Hb. A 1 c targets
Remember The Ultimate Goal: Quality of Life
Cases or Questions?
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