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Peak Nutrition for Metabolic Health PANaMAH
Science Symposium_13th April 2016
1Prof Sally Poppitt (PI), 2Dr Karl Fraser, 1Dr Justin O’Sullivan, 3Dr John Ingram, 1Prof Garth Cooper, 1Dr Rinki Murphy, 1A/Prof Lindsay Plank, 4Dr Greg Jones & team
1University of Auckland, 2Ag Research, 3Plant & Food Research, 4University of Otago
PANaMAH team: NZ & worldwide
A/Prof Greg Jones
Prof Sally Poppitt Dr Ivana Sequiera Louise WeiWei Lu
Wilson Yip, PhD student Dr Rinki Murphy
A/Prof Lindsay Plank
Dr Justin O’Sullivan Tayada Fadason, PhD student
Dr John Ingram PhD student
Dr Karl Fraser Research Assistant
Emily Yee, PhD student Prof Garth Cooper CADET, UK; Hong
Kong; China
Prof Jean-Charles Martin INSERM, Fr
A/Prof Jun Lu
PREVIEW European Union
Focus on obesity and metabolic health in HVN is no surprise…
What are its consequences?
But perhaps a surprise that the transition has happened so quickly, particularly in Asia….
Prof. Majid Ezzati leading the NCD risk factor collaboration
Prof. Majid Ezzati leading the NCD risk factor collaboration
The obesity wave, or tsunami
• Asia is not immune – and facing an EPIDEMIC OF OBESITY as lifestyles change and the population ages
• With China confirmed as the largest global burden o 30% of adults are overweight or obese [400 million = 1/5 of the world’s obesity problem] o Leading to a tsunami of metabolic health problems
• “Paying the price for those extra pounds”
Globally, OVERWEIGHT AND OBESITY approaching 2 BILLION and rising
Globally, TYPE 2 DIABETES approaching 700 MILLION and also rising
• Asia is leading the charge – as lifestyles change, the population ages, and
people gain weight [with China confirmed as the largest global burden]
Asians are at far greater risk of poor metabolic health than their Caucasian counterparts – both at a younger age, and
lower body weight
1WHO, http://www.who.int/mediacentre/factsheets/fs312/en/2015
CONUNDRUM for 2016!
Asian Chinese are much thinner than their US counterparts YET have higher rates both of Diabetes (11.6%)
& pre-Diabetes (estimated ~50%)
http://www.smithstreetchina.com/content_index/m_healthcare.html
And hence Consumers are looking for foods that aid better metabolic health………….
KEY SCIENCE QUESTION: WHY ARE SOME PEOPLE MORE SUSCEPTIBLE [EG. ASIAN] YET OTHERS MORE RESILIENT [EG. CAUCASIAN]?
i. FAT STORAGE [ADIPOSE DEPOSITION] MAY BE AT THE ROOT OF THE
PROBLEM • the TOFI profile = lipid ‘overspill’ • are there early risk markers
ii. CAN WE TARGET THE CAUSE OF THE PROBLEM (failure of the pancreas), AND NOT JUST THE CONSEQUENCES (eg. glucose and insulin)
PEAK NUTRITION FOR METABOLIC HEALTH
And how can we best utilise this knowledge
to develop nutrition (F&B) solutions? CONSUMER NEED/BENEFIT: new foods that help maintain better glucose control prevent type 2 diabetes promote heart health
Nutrition problem = Nutrition solution
KEY SCIENCE QUESTION: WHY ARE SOME PEOPLE MORE SUSCEPTIBLE [ASIAN] YET OTHERS MORE RESILIENT [CAUCASIAN]?
1. FAT DEPOSITION MAY BE AT THE ROOT OF THE PROBLEM
• the TOFI profile = lipid ‘overspill’ • are there early risk markers amenable to F&B intervention?
2. CAN WE TARGET THE CAUSE OF THE PROBLEM (eg. failure of the pancreas), AND NOT JUST THE CONSEQUENCES (eg. high blood glucose) • through dietary (F&B) intervention
PEAK NUTRITION FOR METABOLIC HEALTH
2015 2016 2017 2019
Timeline
What is the TOFI profile and why is it important?
TOFI Thin on the Outside Fat on the Inside
Whilst obesity is strongly associated with poor glucose control & diabetes it may not just be the fat (that you can see) on the outside that’s important but also the fat on the inside
metabolically obese normal weight [MONW]
FAT ON THE INSIDE……….
Particularly fat in
the PANCREAS
from Sapanaro et al., Nutrients, 2015
We hypothesise that: Fat on the inside is more important than fat on the outside Very small amounts of fat in the pancreas (? and/or liver,
muscle, and other organs) may lead to dysregulation of glucose Asian populations may be susceptible to this lipid
‘overspill’ from adipose stores (=‘safe’ storage site) into the pancreas = TOFI; even when young & outwardly slim
This may happen long before glucose levels rise and diabetes develops
WHAT CAUSES THE LIPID ‘OVERSPILL’? = UNKNOWN There may be early biomarkers that predict ectopic lipid
storage & development of TOFI, in the blood
We hypothesise that: Fat on the inside is more important than fat on the outside Very small amounts of fat in the pancreas (? and/or liver,
muscle, and other organs) may lead to dysregulation of glucose ASIAN POPULATIONS MAY BE PARTICULARLY SUSCEPTIBLE TO THIS LIPID
‘OVERSPILL’ from adipose stores (=‘safe’ storage site) into the pancreas = TOFI; even when young & outwardly slim
This may happen long before glucose levels rise and diabetes develops
WHAT CAUSES THE LIPID ‘OVERSPILL’? = as yet UNKNOWN There may be early biomarkers in the blood that predict
ectopic lipid storage & development of TOFI
We hypothesise that: Fat on the inside is more important than fat on the outside Very small amounts of fat in the pancreas (? and/or liver,
muscle, and other organs) may lead to dysregulation of glucose Asian populations may be particularly susceptible to this
lipid ‘overspill’ from adipose stores (=‘safe’ storage site) into the pancreas = TOFI; even when young & outwardly slim
This may happen long before glucose levels rise and diabetes develops
WHAT CAUSES THE LIPID ‘OVERSPILL’? = as yet UNKNOWN… but there may be early biomarkers in the blood that
predict this ‘overspill’ & development of TOFI
SCENARIO – 2 women walk into our research clinic in Auckland…
A little overweight BMI=26kg/m2
also high glucose = ?diabetic
!!!
Why are Asian people so susceptible – even when they are lean?
Obese BMI=37kg/m2
We measure their blood glucose
Asia
n
Cau
casia
n
high glucose = ?diabetic
Exactly as we would predict
Surprisingly
Human Nutrition Unit
CONCLUSION: it’s very difficult to predict who’s at risk and who isn’t - we need better (and earlier)
markers
Glucose is a very ‘blunt’ marker of early risk
Age (y)
Weight (kg)
BMI (kg/m2)
Glucose Pancreatic fat (%)
18 52 20 normal low
25 55 21 normal HIGH
30 56 22 normal HIGH
38 58 23 HIGH HIGH
Glucose is a very ‘blunt’ marker for people without diabetes Not a good predictor of who will suddenly worsen Or when they will worsen; BUT ectopic fat probably is a good predictor and may be a very good early marker
BMI and total body fatness are not always good predictors of risk ; particularly in Asian populations who often have raised glucose even within lean range BMI
Asian Chinese
But, ectopic fat is difficult to measure Magnetic Resonance Imaging (MRI)
Not a routine clinical assessment, expensive, claustrophobic No ionising radiation, good safety profile
Pancreas
AIM: identify early blood markers of ectopic fat and poor glucose control using the
HVN METABOLOMICS PLATFORM
? Are there better early markers – metabolomics small molecules, metabolites ? Can we target these markers with F&Bs
Correlation with % pancreatic fat
small m
olecules, metabolites in circulation
? Are there better early markers – metabolomics small molecules, metabolites ? Can we target these markers with F&Bs
Correlation with % pancreatic fat
Aim: identify early blood markers of ectopic fat and poor glucose control using the
HVN METABOLOMICS PLATFORM Dr Karl Fraser, Ag Research, NZ Dr Jean-Charles Martin, INSERM, Fr
HVN Metabolomics
Hub
small m
olecules, metabolites in circulation
? Are there better early markers – metabolomics small molecules, metabolites ? Can we target these markers with F&Bs
Correlation with % pancreatic fat
Aim: identify early blood markers of ectopic fat and poor glucose control using the
HVN METABOLOMICS PLATFORM Prof Garth Cooper, CADET, U of Manchester, UK and U of Auckland, NZ [MBIE Treating Diabetes]
Visiting Professor • U of Hong Kong • Chinese Acad Sci
small m
olecules, metabolites in circulation
GLOBAL LEADER: METABOLOMICS & MET HEALTH – T2D, BRAIN/COGNITION
PANaMAH: Phase 1 Risk profile assessment
TOFI-MRI, early biomarkers
PATHWAY ANALYSIS: SMART MODELLING IN SILICO and validation studies
PANaMAH: Phase 2 Meal studies to determine food components that
(i) modulate risk biomarkers (ii) promote healthy organ structure/function (pancreas)
PRO
GRAM O
VERVIEW
Blood Tissue (bariatric cohort)
Predict foods that modulate risk profile
PANaMAH: Phase 1 Risk profile assessment
Asian & Caucasian adults: BMI 20-45kg/m2; = range of risk profiles based on plasma glucose & HbA1c
N=400+, metabolomics profile
Asian N=200, % fat DeXA
Asian
Cau- casian
N=100+, pancreatic fat, MRI
Asian Caucasian
April – Dec 2016
Dr I
vana
Seq
ueira
Lo
uise
Wei
Wei
Lu
Wils
on Y
ip, P
hD
Caucasian
Dr R
inki
Mur
phy,
Dia
bete
s spe
cial
ist
A/Pr
of L
inds
ay P
lank
, bod
y co
mpo
sitio
n A/
Prof
Jun
Lu, M
RI c
olla
bn
FUNCTIONAL FOOD COMPONENTS – identify new interactions between foods, nutrients, bioactive components and existing & novel biomarkers of metabolic health FOOD TARGETS: Animal protein/amino acids, prebiotic oligsaccharides (eg galactoligosacharides), dietary fibre, phytochemicals BIOMARKERS: glucose regulation, insulin sensitivity (dynamic and static markers), novel predictive metabolic risk markers within proteome, metabolome, transcriptome, epigenome, liver fat, ectopic fat stores, intra-abdominal fat stores, pro-inflammatory cytokines
Smarter prediction of foods and food components that can target dysregulated pathways: • glucose, insulin • small molecules, metabolites (metabolome) • pancreas & liver….
PATHWAY ANALYSIS: SMART MODELLING – IN SILICO & VALIDN
Dr Justin Dr John O’Sullivan Ingram
PANaMAH: Phase 2 feeding studies to determine food components
that (i) modulate risk biomarkers
2017 to 2019
Dr I
vana
Seq
ueira
Lo
uise
Wei
Wei
Lu
Wils
on Y
ip, P
hD
PANaMAH: Phase 2 feeding studies to determine food components
that (ii) promote healthy organ structure/function
2017 to 2019
Dr I
vana
Seq
ueira
Lo
uise
Wei
Wei
Lu
Wils
on Y
ip, P
hD
Pancreas Liver
INTERDISCIPLINARY FOCUS OF: • Clinical studies • Biomarkers – validate
established & investigate novel underpinned by: • Food science • Asian consumer preferences
AIM QUICKER, CHEAPER, SMARTER
CLINICAL VALIDATION FOR REGULATORS
Key OUTPUT = Clinical Validation
HVN funding to de-risk fundamental research for Industry and provide future opportunities
You can’t do anything on your own….
Number of existing programs feeding into PANaMAH both nationally & internationally
Industry Reference Group: Incl. Zespri, Comvita, Sanitarium, Diabetic Foods Ltd
KEY PROJECTS: UoO metabolic health biobank (~10,000 NZ adults) led by A/Prof Greg Jones, SOM
Industry Reference Group: Incl. Zespri, Comvita, Sanitarium, Diabetic Foods Ltd
KEY PROJECTS: recently funded MBIE metabolic health collaboration between NZ researchers and A* in Singapore,
through the HVN Metabolomics Hub
Healthy Met Syn
Brenan Durainayagam PhD student
KEY PROJECTS: metabolomic interrogation of metabolic syndrome, in a smaller cohort of Asian Chinese and
Caucasian women [=combine datasets]
Karl Fraser
PANaMAH update: recruitment is underway for TOFI….
Caucasian Asian Chinese
Dr Ivana Sequiera, Louise WeiWei Lu, Wilson Yip PhD student