GENOMIC AND LIFESTYLE PREDICTORS OF FOETAL OUTCOME RELEVANT TO DIABETES AND OBESITY AND THEIR RELEVANCE TO PREVENTION STRATEGIES IN SOUTH ASIAN PEOPLES [GIFTS]

Co-ordinator: Graham A HitmanBarts and The London QMUL

Deputies:Akhtar Hussain, Oslo, NorwayRanjan Yajnik, Pune, India

GLOBAL PREVALENCE OF TYPE 2 DIABETES

DIABETES IN NORTH EAST LONDON

THE IMPACT OF DIABETES IN EAST LONDON

Years of life lost due to mortality from diabetes*, 2005-07

Westminster PCTKingston PCTBexley Care TrustLewisham PCTBromley PCT

Barking and Dagenham PCTRedbridge PCTHounslow PCTEnfield PCTHaringey Teaching PCTCroydon PCTGreenwich Teaching PCTLambeth PCTNewham PCTWaltham Forest PCT

Hammersmith and Fulham PCTEaling PCTCamden PCTIslington PCTBrent Teaching PCTSouthwark PCTCity and Hackney Teaching PCT

Wandsworth Teaching PCT

Kensington and Chelsea PCTSutton and Merton PCT

Havering PCTHillingdon PCTHarrow PCTBarnet PCT

Richmond and Twickenham PCT

Tower Hamlets PCT

* Directly age-standardised rates, for age group <75 Source: Information Centre

London SHA – 3.97England – 4.01

THE MULTIFACTORIAL AETIOLOGY OF TYPE 2 DIABETESTHE MULTIFACTORIAL AETIOLOGY OF TYPE 2 DIABETES

Genetic predisposition

Foetal influences

Child and adult influences

IS THE EPIGENOME ONE OF THE MISSING ‘FAMILIAL’ FACTORS?

Genome Environment Phenotype

Environment

epigenome

i.e. diet, infections, smoking, toxins, ageing

Changes to the maternal environment such as poor nutrition and hyperglycaemia may

‘programme’ type 2 diabetes in offspring

Risk of Type 2 diabetes

Hertfordshire birth cohort

Low birth weight

Dutch hunger winter

Lack of protein

Pune, India

Low vitamin B12

Pima Indians

Gestational diabet

FOETAL PROGRAMMING

MATERNAL VIT B12 & FOLATE IN PREGNANCY AND THE EFFECTON THE OFFSPRING AT 6 YEARS OF AGE

Vitamin B12

Red cell folate

HOMA-R

Pune Maternal Nutrition StudYajnik CS et al, Diabetologi

(2008

GIFTS WORK PACKAGES (WP)

OVERALL PROGRAM IN SOUTH ASIANS

�Lifestyle and Nutrition from Pre-conception to Early Childhood

�Characterisation of Gene and Environment Interactions

�Clinical Translation of the Findings of GIFTS Programme

�WP1: Scientific management and co-ordination (Graham A Hitman, Barts and The London, QMUL)

WP2: Hussain (Oslo), Khan (Dhaka), Basit (Karachi) and QMUL HOW DO LIFESTYLE AND NUTRITION AFFECT PREGNANCY AND FOETAL OUTCOMES RELEVANT TO METABOLIC DISEASE IN THE VARIOUS SETTINGS?

�1,600 mothers and offspring (550 from Bangladesh, 550 from East London, 300 from Pakistan and 200 from Oslo)

�Literature review, analysis of pre-existing data and meta-analysis

�Use results to help design complex intervention for WP3&4

WP3&4: Ranjan Yajnik (Pune), Caroline Fall (Southampton) and all LIFESTYLE AND NUTRITION FROM PREGNANCY TO EARLY CHILDHOOD – PILOT INTERVENTIONS

PILOT PRAGMATIC INTERVENTION TRIAL (Hussain, Hitman, Khan & Basit)

�Recruit 1200 expectant mothers (600 from Bangladesh and 600 fromPakistan) from first pregnancy detection by community workers

�Randomised to ‘usual care’ or a complex personalised intervention

�Study metabolic outcomes of mother & child

�Feasibility of follow-up from birth to up to 1 year

WP3&4: Ranjan Yajnik (Pune), Caroline Fall (Southampton) and all LIFESTYLE AND NUTRITION FROM PREGNANCY TO EARLY CHILDHOOD – PILOT INTERVENTIONS continued

Feasibility of B12 supplementation in the Pune Maternal Nutrition Study (Yajnik)

�MRC funded intervention in Pune India pre-conception. GIFTS will finance biochemical assays to understand the mechanism of action of B12 replacement of value to future European based interventions.

UCL/DAB metabolic follow-up at age 3 years (Costello and Kishwar)

�WT funded community empowerment project in rural Bangladesh to improve maternal, infant and child health outcomes of which GIFTS will fund pilot studies directed to the metabolic component

CHARACTERISATION OF GENE ENVIRONMENTAL INTERACTIONS

WP5: Shah Ebrahim, Yoav Ben-Shlomo (Delhi/Bristol) and Sanjay Kinra (LSHTM)

�Development of more cost effective nutritional and DNA assays

WP6: Tim Frayling (Exeter), Giraj Chandak (Hyderabad), George Davey-Smith (Bristol), GAH

�To study the genetic determinants of foetal programming and response to targeted intervention using the metabochip in mother-child pairs in 1000 families from the intervention cohorts and 650 mother child-pairs from Pune Maternal Nutrition Study

WP7: Vardhman Rakyan, Sarah Finer and Graham Hitman (QMUL)

�To study the epigenetic determinants of foetal programming and response to targeteintervention using the illumina 450k methylation chips in 400 Bangladeshi offspring from the intervention cohorts

CLINICAL TRANSLATION OF THE FINDINGS

WP8: SME BAP Health Outcomes (Pablo Rebollo; Spain)

HEALTH ECONOMIC ANALYSIS POLICY IN EUROPE AND SOUTH ASIA

�Focusing on predictors of metabolic childhood outcomes in pregnancy and intervention design

WP9: Trish Greenhalgh, Khalid Khan, Shanti Vijayaraghavan (QMUL)

DEVELOPING BEHAVIORAL AND NUTRITIONAL INTERVENTIONS IN EUROPE IN SOUTH ASIANS

�Systematic review of interventions to improve mother and child outcomes in obese pregnant Asian women

�Qualitative research to explore the illness experience and cultural perspectives of gestational diabetes in Asian women

CLINICAL TRANSLATION (2)

WP10: Angela Harden (UEL) and Bjorgulf Clausen (Oslo)

�To identify the barriers to, and facilitators of, accessing antenatal care and other pregnancy-related services amongst South Asian women living in urban areas in Europe and South Asia

WP11: SME INSTRUCT (Martin Adler) & Peter Shwarz (Dresden), Jaakko Tuomulehto (Helsinki), Sheila Adam (UEL)

�Dissemination of information, training and technology exchange and informing public health

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PARTNERSUNIVERSITY OF LONDON, UK

BARTS AND THE LONDON, QMUL, UK

Graham A Hitman, Sarah Finer, Vardhman Rakyan , Khalid Khan, Trisha Greenhalgh

LONDON SCHOOL HYGIENE AND TROPICAL MEDICINE, UK

Sanjay Kinra

UNIVERSITY COLLEGE LONDON, UK

Anthony Costello

UNIVERSITY OF EAST LONDON & NEWHAM UNIVERSITY NHS TRUST, UK

Angela Harden, Sheila Adam

UNIVERSITY OF SOUTHAMPTON, UK

Caroline Fall

UNIVERSITY OF EXETER, UK

Tim Frayling

UNIVERSITY OF DRESDEN, GERMANY

Peter Schwartz

INSTRUCT AG, MUNICH, GERMANY

Martin Adler

BAP HEALTH OUTCOMES, OVIEDO, SPAIN

Pablo Rebollo

UNIVERSITY OF OSLO, NORWAY

Akhtar Hussain, Stein Vaaler,Gerd Homboe Ottesen, Bjogulf Claussen

UNIVERSITY OF HELSINKI, FINLAND

Jaakko Tuomilehto

KING EDWARD MEMORIAL HOSPITAL, PUNE, INDIA

Ranjan Yajnik

PUBLIC HEALTH FOUNDATION OF INDIA, DELHI, INDIA & UNIVERSITY OF BRISTOL

Shah Ebrahim, George Davey-Smith, Yoav Ben-Shlomo

COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH, HYDERABAD, INDIA

Giraj Chandak

BAQAI INSTITUTE OF DIABETOLOGY AND ENDOCRINOLOGY, KARACHI, PAKISTAN

Abdul Basit, Samad Sheera

DIABETES ASSOCIATION OF BANGLADESH,DHAKA, BANGLADESH

Azad Khan, Kishwar Azad , Liaquat Ali

GIFTS SUMMARY

� GIFTS is an ambitious program targeting early life programming as an opportunity for the prevention of diabetes and obesity in people from South Asia living either in their home countries or Europe

� However, to make a significant impact we need to explore opportunities for greater international cooperation and a willingness to share data, resources and expertise to the common good Four cluster projects studying diabetes

and obesity in specific populations