Science Symposium_13th April 2016 Peak Nutrition for Metabolic Health PANaMAH 1 Prof Sally Poppitt (PI), 2 Dr Karl Fraser, 1 Dr Justin O’Sullivan, 3 Dr John Ingram, 1 Prof Garth Cooper, 1 Dr Rinki Murphy, 1 A/Prof Lindsay Plank, 4 Dr Greg Jones & team 1 University of Auckland, 2 Ag Research, 3 Plant & Food Research, 4 University of Otago Host Institution
PANaMAH team : NZ & worldwide PREVIEW European Dr John Ingram Union PhD student Prof Sally Poppitt Dr Ivana Sequiera Louise WeiWei Lu A/Prof Jun Lu Wilson Yip, PhD student Dr Rinki Murphy A/Prof Lindsay Plank Dr Justin O’Sullivan Dr Karl Fraser Prof Garth Cooper Tayada Fadason, PhD student Research Assistant CADET, UK; Hong Emily Yee, PhD student Kong; China A/Prof Greg Jones Prof Jean-Charles Martin INSERM, Fr
Focus on obesity and metabolic health in HVN is no surprise… What ar are i e its ts co consequence ces?
But perhaps a surprise that the transition has happened so quickly, particularly in Asia….
Prof. Majid Ezzati leading the NCD risk factor collaboration
The obesity wave, Prof. Majid Ezzati or tsunami leading the NCD risk factor collaboration
Globally, O VERWEIGHT AND O BESITY approaching 2 B ILLION and rising • Asia is not immune – and facing an E PIDEMIC OF O BESITY 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, T YPE 2 D IABETES approaching 700 M ILLION 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 1 WHO, 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%) And hence Consumers are looking for foods that aid better metabolic health…………. http://www.smithstreetchina.com/content_index/m_healthcare.html
P EAK N UTRITION FOR M ETABOLIC H EALTH K EY S CIENCE Q UESTION : W HY ARE SOME PEOPLE MORE S USCEPTIBLE [ EG . A SIAN ] YET OTHERS MORE R ESILIENT [ EG . C AUCASIAN ]? i. F AT S TORAGE [A DIPOSE D EPOSITION ] MAY BE AT THE R OOT OF THE And how can we best utilise this knowledge P ROBLEM to develop nutrition (F&B) solutions? • the TOFI profile = lipid ‘overspill’ • are there early risk markers C ONSUMER N EED /B ENEFIT : new foods that help maintain better glucose control prevent type 2 diabetes promote heart health C AN WE TARGET THE CAUSE OF THE PROBLEM (failure of the pancreas) , ii. AND NOT JUST THE CONSEQUENCES (eg. glucose and insulin) Nutrition problem = Nutrition solution
P EAK N UTRITION FOR M ETABOLIC H EALTH K EY S CIENCE Q UESTION : W HY ARE SOME PEOPLE MORE S USCEPTIBLE [A SIAN ] YET OTHERS MORE R ESILIENT [C AUCASIAN ]? 1. F AT D EPOSITION MAY BE AT THE R OOT OF THE P ROBLEM 2015 2016 2017 2019 • the TOFI profile = lipid ‘overspill’ • are there early risk markers amenable to F&B intervention? Timeline 2. C AN 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
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]
F AT ON THE I NSIDE ………. 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 W HAT 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 A SIAN 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 W HAT 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 W HAT CAUSES THE LIPID ‘ OVERSPILL ’? = as yet UNKNOWN … but there may be early biomarkers in the blood that predict this ‘overspill’ & development of TOFI
Why are Asian people so susceptible – even when they are lean? S CENARIO – 2 women walk into our research clinic in Auckland… Human Nutrition Unit Exactly as we Obese Asian Caucasian would predict BMI=37kg/m 2 high glucose = ?diabetic We measure their blood glucose Surprisingly also high A little overweight !!! glucose = BMI=26kg/m 2 ?diabetic
C ONCLUSION : 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 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 Age Weight BMI Glucose Pancreatic (kg/m2) (y) (kg) 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; Asian Chinese BUT ectopic fat probably is a good predictor and may be a very good early marker
But, ectopic fat is difficult to measure Magnetic Resonance Imaging (MRI) Pancreas Not a routine clinical assessment, expensive, claustrophobic No ionising radiation, good safety profile
AIM: identify early blood markers of ectopic fat and poor glucose control using the HVN METABOLOMICS PLATFORM small molecules, metabolites in circulation Correlation with % pancreatic fat ? Are there better early markers – metabolomics small molecules, metabolites ? Can we target these markers with F&Bs
Aim: identify early blood markers of ectopic fat and poor glucose control using the HVN METABOLOMICS PLATFORM small molecules, metabolites in circulation Dr Karl Fraser, Ag Research, NZ Dr Jean-Charles Martin, INSERM, Fr HVN Metabolomics Hub Correlation with % pancreatic fat ? Are there better early markers – metabolomics small molecules, metabolites ? Can we target these markers with F&Bs
Aim: identify early blood markers of ectopic fat and poor glucose control using the HVN METABOLOMICS PLATFORM small molecules, metabolites in circulation Prof Garth Cooper, CADET, U of Manchester, UK and U of Auckland, NZ [ MBIE Treating Diabetes ] G LOBAL LEADER : M ETABOLOMICS & M ET H EALTH – T2D, B RAIN /C OGNITION Visiting Professor • U of Hong Kong • Chinese Acad Sci Correlation with % pancreatic fat ? Are there better early markers – metabolomics small molecules, metabolites ? Can we target these markers with F&Bs
P ROGRAM O VERVIEW PANaMAH: Phase 1 Blood Risk profile assessment Tissue TOFI-MRI, early biomarkers (bariatric cohort) Predict foods P ATHWAY A NALYSIS : S MART M ODELLING that modulate I N S ILICO and validation studies risk profile PANaMAH: Phase 2 Meal studies to determine food components that (i) modulate risk biomarkers (ii) promote healthy organ structure/function (pancreas)
PANaMAH: Phase 1 A/Prof Lindsay Plank, body composition Dr Rinki Murphy, Diabetes specialist Risk profile assessment Asian & Caucasian adults: BMI 20-45kg/m 2 ; A/Prof Jun Lu, MRI collabn = range of risk profiles based on plasma glucose & Hb A1c N=400+, metabolomics profile N=200, % fat DeXA Asian N=100+, pancreatic fat, MRI Asian Dr Ivana Sequeira Louise WeiWei Lu Wilson Yip, PhD Cau- Asian Caucasian Caucasian casian April – Dec 2016
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