Swiss Re Ag · SIX:SREN
Swiss Re — Investor Presentation (October 2023)
19 slides from Swiss Re's investor presentation, Oct 9, 2023
Slide 1: Why is type 2 diabetes linked to Alzheimer's disease?
Why is type 2 diabetes linked to Alzheimer’s disease? Stephen C. Cunnane, PhD Professor and Endowed Research Chair in Clinical Ketotherapeutics Department of Medicine and Research Center on Aging Université de Sherbrooke, Sherbrooke, QC, CANADA Fixing Metabolic Health Meeting Swiss Re Centre for Glo
Slide 2: Disclosures
Disclosures PUBLIC PRIVATE CIHR, CRC, FRQS, MITACS, NSERC, Nestlé Health Science Research Center on Aging Abbott, Cargill, Cerecin, Swiss Re NON-PROFIT Alzheimer Society Research Program (Canada) Alzheimer Association (USA) NOTE The contents of this presentation are for research purposes only and sh
Slide 3: Glucose-insulin dysregulation: a major challenge as we age
Glucose-insulin dysregulation: a major challenge as we age Fasting 70 years old 25 years old Oral glucose (75 g)
Slide 4: Metabolically, the brain is a hybrid car
Metabolically, the brain is a hybrid car
Slide 5: Brain energy metabolism: Two distinctly different strategies for the two main fuels
Brain energy metabolism: Two distinctly different strategies for the two main fuels
Slide 6: Ketones spare brain glucose uptake
Ketones spare brain glucose uptake C M R g ( m o l/1 0 0 g /m in ) -4 c in g u la te S u b c o r tic a l brain glucose uptake P a rie ta l o c c ip ita l fro n ta l (mol/100 g/min) te m p o ra l o th e rs -6 -8 R = -0.91 p<0.0001 -1 0 +3 +4 +5 +6 brain ketone ( m o l / (mol/100 C M R au
Slide 7: Ketones to improve (rescue) brain energy supply during aging
Ketones to improve (rescue) brain energy supply during aging: inspired by their role during brain development in infants (Cunnane and Crawford, J Human Evolution, 2014) • Mild hyperketonemia is normal in infants (0.5 – 1.0 mM ketones). • 3-4 times more rapid brain ketone uptake in infants than in ad
Slide 8: Impaired brain energy metabolism in MCI and AD is specific to glucose
Impaired brain energy metabolism in MCI and AD is specific to glucose; no brain deficit in the capacity (K) to take up ketones Glucose Ketone (cross-sectional data: n ~20/group) Glucose Significant decrease No decrease, some increase (Cunnane et al. Nature Reviews Drug Discovery, 2020)
Slide 9: Impaired brain energy metabolism in MCI and AD is specific to glucose
Impaired brain energy metabolism in MCI and AD is specific to glucose; no brain deficit in the capacity (K) to take up ketones Glucose Ketone (cross-sectional data: n ~20/group) Glucose Significant decrease No decrease, some increase Global glucose deficit: 20-40 g/d (Cunnane et al. Nature Reviews D
Slide 10: Impaired brain energy metabolism in MCI and AD is specific to glucose
Impaired brain energy metabolism in MCI and AD is specific to glucose; no brain deficit in the capacity (K) to take up ketones Glucose Ketone (cross-sectional data: n ~20/group) Glucose ROBUST OBSERVATION: 4 different techniques reported by 7 different groups confirm that brain ketone uptake is inta
Slide 11: Ketogenesis from MCT is largely intact in pre-diabetic older women
Ketogensis from MCT is largely intact in pre-diabetic older women (Vandenberghe et al. Adv Physiol Nutr Metabolism, 2017) • N=10/gp, 67 y old • kMCT: 2 X 15 g/d X 5 d • N=10/gp, 67 y old • kMCT: 2 X 15 g/d X 5 d
Slide 12: Benefic: kMCT improved outcomes in 5/5 cognitive domains
Benefic: kMCT improved outcomes in 5/5 cognitive domains (Fortier et al. Alzheimer’s & Dementia, 2019, 2021)
Slide 13: Benefic: kMCT improved outcomes in 5/5 cognitive domains
Benefic: kMCT improved outcomes in 5/5 cognitive domains (Fortier et al. Alzheimer’s & Dementia, 2019, 2021) A 1 word improvement in a 16-item episodic memory test has been predicted to delay AD onset by 1-3 years (Auriacombe et al. 2010, Grober et al. 2018)
Slide 14: Brain ketone uptake doubles after a supervised walking intervention in Alzheimer's disease
Brain ketone uptake doubles after a supervised walking intervention in Alzheimer’s disease (n=10) 8 km/wk, 4 km/h, 12 wk (Castellano et al. J Alz Disease, 2017)
Slide 15: Improving metabolic health in retirement homes
Improving metabolic health in retirement homes: Can we protect against type 2 diabetes and Alzheimer disease? Standard menu Standard menu 30% ↓ CHO 30% ↓ CHO meals meals Time, 24 h days (h) Time, 24 h days (h) • 84 y old, 10 d feasibility study, 30% ↓ CHO intake GOAL: scale up to multi-center trial,
Slide 16: Regional brain glucose hypometabolism in young women with insulin resistance due to PCOS
Regional brain glucose hypometabolism in young women with insulin resistance due to polycystic ovary syndrome (Castellano et al, PLOS1, 2016) 24 years old; normal BMI; mild deficit in working memory ~10% glucose hypometabolism 10-14% glucose hypometabolism in the parietal, temporal cortex; in the fr
Slide 17: Regional brain glucose hypometabolism in young women with insulin resistance due to PCOS
Regional brain glucose hypometabolism in young women with insulin resistance due to polycystic ovary syndrome (Castellano et al, PLOS1, 2016) 24 years old; normal BMI; mild deficit in working memory ~10% glucose hypometabolism 10-14% glucose hypometabolism in the parietal, temporal cortex; in the fr
Slide 18: Metabolic health lets the hybrid car work as it should
Metabolic health lets the hybrid car work as it should • Dietary energy / carbohydrate restriction to allow endogenous ketogenesis. • Never too young or too old to improve glucose regulation. • Ketones can safely meet ≥75% of the brain’s energy requirements. • Ketone supplements (kMCT, salts, esters
Slide 19: THANK YOU!
Research team and collaborators Funding partners Particpants THANK YOU!