Diabetes Research Envisioned and Accomplished in Manitoba

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2 Diabetes Research Envisioned and Accomplished in Manitoba Jonathan McGavock PhD Robert Wallace Cameron Chair in Evidence-based Child Health Department of Pediatrics and Child Health, Faculty of Medicine Manitoba Institute of Child Health

3 Why do We do This?

4 Incident cases Referrals for T2D-Youth in Manitoba

5 incidence per 100,000 children/year Rates of T2DM in in Youth in Canada BC Alberta Manitoba Atlantic Quebec Ontario Amed S, Dean H et al. Diabetes Care April 2010

6 Why Study T2D in Youth? Percentage of total new cases of diabetes that are T2D Tokyo Montana Tapei Winnipeg New York South Carolina Ventura, CA Bankok Australia India France Autria Sweden Pinhas-Hamiel et al, J. Peds (5):693

7 Why is this so Important? End-Point HR Major Complication ( ) Retinopathy ( ) Renal Diagnosis ( ) Renal Failure ( ) Dialysis ( ) Dart et al. Diabetes Care 2012; 35: 1265

8 Research Questions 1) Why did my children get diabetes? 2) How can I prevent them from being on dialysis? 3) How can I prevent my grandchildren from getting diabetes?

9 DREAM Theme Research Model

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11 WHY DID MY CHILDREN GET DIABETES?

12 Gestational Determinants of T2D in Youth Odds of T2D according to gestation diabetes status Young K, Arch Ped Adol Med :2224 Franks PW. Diabetes ;55:460

13 Pre-Gestational Diabetes GDM Pre-Gestational Diabetes Mendelson M et al. Ped Diabetes. 2011:12:219

14 Prevalence of T2DM in offspring of mothers with pre-gestational T2DM SEARCH* Yale Obesity Clinic** Next Generation 43% 60% % 4% <10 yrs >10 yrs 12-18yrs * SEARCH SG. Pediatrics. 2006;118:1510. ** Sinha et al. NEJM 2002;346:802

15 Next Generation Cohort

16 Translational Approach

17 Translational Research

18 Next Generation Sequencing

19 Fatty liver as a risk factor for T2D Wicklow, Wittmeier et al. Diabetes Care. 2012

20 Study Population Variables Healthy Weight (n = 11) Overweight < 5.5 mg/g (n = 68) Overweight 5 mg/g (n = 30) Age (years) 16 (13-17) 15 (13-18) 15 (13-17) Male/Female 5/6 14/54 16/14 % body fat 23% 37% 39% BMI z-score 0.1 ( ) 1.8 ( ) ab 2.1 ( ) a Waist Circumference (cm) 72.1 ( ) 97.8 ( ) ab ( ) a

21 Insulin Sensitivity (mu/ml/min) Hepatic Steatosis and IR 12 p < p < Lean <2 2-5 >5 T2DM Hepatic Fat Content (%) Overweight

22 Glucose (mmol/l) Hepatic Triglyceride and Impaired Glucose Tolerance 8 Lean OW <5 mg/g OW >5mg/g ± ± ± Base

23 Hepatic Steatosis vs VAT Prevalence of Met. Syndrome P < P < 0.01 Glucose AUC Low IHTG High IHTG Low VAT High VAT 600 Low IHTG High IHTG Low VAT High VAT Matched VAT Matched IHTG Matched VAT Matched IHTG

24 HOW CAN I PREVENT MY CHILDREN FROM COMPLICATIONS?

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26 icare Cohort Pre-clinical neuropathy Pre-clinical Cardiomyopathy Nephropathy Risk Factors 24hr BP, PA Sleep Diet Funded by CDA to Dart A

27 Preliminary Findings (n=149) Variable Renal Injury (n=45) No Injury (n=94) Age (yrs) 15.7 (3) 15.3 (4) Duration of Diabetes (yrs) 3.0 (3.6) 2.5 (3.1) BMI Z score 2.3 (1.2) 2.3 (1.0) HbA1c (%) 8.7 (4.3) 11.4 (2.5) GFR 127 (14) 134 (13) ACR 0.34 (0.79) 6.2 (11)

28 % of Wear Time Hypertension * * MA No-MA BP Load Sleep BP Load

29 MHC Total Score Mental Health Positive Mental Health (MHC) Manitoba Canada Males Females Diabetes No Diabetes White Non-White All icare CCHS Mental Health 2012

30 K6 Total Score Mental Health 9.00 Kessler Distress (K6) Manitoba Canada Males Females Diabetes No Diabetes White Non-White All icare CCHS Mental Health 2012

31 Next Steps

32 Next Steps

33 Fetal Origins of Diabetes icare Next Gen Study

34 LV Filling Rate Pre-Gestational DM and DCM % -5% Control T2D T2D-GDM

35 Pre-Gestational DM and DCM % % CTL T2D GDM 1 IVS E`/A` LAT E`/A`

36 HOW CAN I PREVENT MY GRANDCHILDREN FROM DIABETES?

37 RESEARCH QUESTIONS 1. Will the policy reduce the number of inactive youth in Manitoba? 2. Will the policy prevent the major decline in PA levels between grade 9 and 12? 3. Does the school environment determine the effectiveness of the policy? 4. What factors identified by stakeholders facilitate effective policy implementation?

38 MIPASS Policy Evaluation YOUTH HEALTH SURVEY 4 pages, 51 questions Multiple choice, machine scannable minutes to complete (short) Includes questions on tobacco, nutrition, physical activity, self esteem and school connectedness CENSUS of PA in MB 46,919 students participated in the survey ~33,000 in grades of these schools included grade 9 12 All 11 Manitoba Regional Health Authorities participated

39 Research Design 1 How do you know it s the policy? Rates of inactivity 2008 n = 33,000 Rates of inactivity 2012 n = 33,000

40 Research Design 1 Policy No Policy

41 Research Design #2 1) Cohort study of ~700 adolescents between grades 9 and 12 in Manitoba 2) 32 schools / school beginning in Followed to ) Randomly Selected with 40% rural 4) Parallel cohort of 800 youth in Alberta

42 Assessment of Physical Activity Actical (minimeter) 7 day data collection Data collected every 15 seconds Youth asked to wear it for a minimum of 10 hrs daily Provided with a minimal incentive to wear the unit Same research assistant for all 4 years Eslinger Tremblay APNM 2008

43 Example of a Good file

44 Example of an acceptable file

45 Example of an inacceptable file

46 MVPA TIME (mins/day) Results Question #2 80 Weekday Weekend * * 0 BOYS GIRLS

47 MVPA (mins/day) Policy type? No PE >50%in <50%in Centre for Physical Activity and Cardiometabolic Health in Youth

48 Individual Trajectories

49 Individual Trajectories

50 Applied Health Chair in Resilience and Obesity in Indigenous Youth Jonathan McGavock PhD Department of Pediatrics and Child Health University of Manitoba Brian Torrance MSc Everactive Schools Rob Santos PhD Healthy Child Manitoba

51 In a Nutshell. Health Disparities in Indigenous Youth Obesity Inequity Diabetes Inequity 60% 25% T2D Trends Life Expectancy (yrs) 0 `85-95 `95-05 `05-14 McGavock Curr. Diab. Reports

52 In a Nutshell. Everything we are doing for obesity is wrong, for Indigenous youth it s immoral Mental Health Distress T2D Cdn Avg T2D Cnd Avg -17 Quality of Life 70 Poverty Total Emotional Social Dart Diabetes Care 2010; Scwimmer JAMA T2D Cnd Avg

53 In a Nutshell. Residential Schools Transgenerational Stress Loss of Language Loss of Culture Loss of Land King M. et al. Lancet 2009

54 In a Nutshell. What are we Proposing? Willows, Delormier, Hanley APNM 2012

55 Defining the Impact Resilience as a Path to Wellness Central Obesity Peer Control Central Obesity AYMP Control 1 Obesity 8 Self-Efficacy Proposed Sites Peer Control Current Sites McGavock JAMA Peds 2014; Pediatrics AYMP Control

56 Key Opportunities Partnerships

57 Community Input

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59 Why do We do This?

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61 Living with Hope

62 It is easier to build strong children than to repair broken men - Frederick Douglass

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64 Acknowledgements Improving Clinical Care of Children with Diabetes Through World Class Research

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66 Acknowledgements icare Team Meaghan Woo, Danielle Rand, Caitlynn McFayden, Sherri-Lynn Wingfield Dr. Allison Dart and icare Investigator Team Dr. Davinder Jassal and Sheena SBRC Susan Acland and CRU DREAM Theme for financial support