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BRING SUNDHEDSDATA I SPIL PROF. DANIEL R. WITTE AARHUS UNIVERSITY, DEPARTMENT OF PUBLIC HEALTH DANISH DIABETES ACADEMY AARHUS 14-03-2017

GLUCOSE, INSULIN AND THE PANCREAS

THE MAIN COMPLICATIONS OF DIABETES Re9nopathy Coronary Heart Disease Cerebrovascular Disease Nephropathy Neuropathy Peripheral Vascular Disease

DIABETES SUBTYPES (2014) Groop & Pociot. Mol Cell Endocrinol. 2014 Jan 25;382(1):726-39

CHALLENGES Understanding mechanisms that lead to diabetes and its complications Preventing diabetes: Physiology Screening? Primary prevention Changing health behaviours Improving patient care: Treatment effectiveness Understanding risk Removing barriers

CENTRAL CONSIDERATIONS IN EPIDEMIOLOGY Is an observed association true? What are the alternatives? Chance Bias Selection Information Confounding

THE WHITEHALL II STUDY British observational, occupational cohort study 10,308 participants 35-55 years old Men (70%) and women (30%) Started in 1985 18 years of follow-up with OGTT (1991-2009) Phase 3 Phase 5 Phase 7 Phase 9 Phase 4 Ques9onnaire Phase 6 Ques9onnaire Phase 8 Ques9onnaire OGTT Clinical exam. Ques9onnaire OGTT Clinical exam. Ques9onnaire OGTT Clinical exam. Ques9onnaire OGTT Clinical exam. Ques9onnaire 1991-1994 1997-1999 2002-2004 2007-2009

Window of opportunity for preven9on Tabák AG, Lancet. 2009 Jun 27;373(9682):2215-21. Tabák AG, Lancet. 2012 Jun 16;379(9833):2279-90

FINDING DIABETES PATIENTS IN THE GENERAL POPULATION General Population High Risk Population Patients with undiagnosed diabetes Patients with known diabetes

THE ADDITION STUDY Denmark UK Netherlands Annelli Sandbæk, Guy Ruden, Stephen Sharp, Nick Wareham, Else-Marie Dalsgaard, Rimke Vos, David Webb, Greg Irving, Daniel Wide, Torsten Lauritzen, Melanie Davies, Kamlesh Khun9, Simon Griffin Clinical trial registra:on number NCT00237549

HOW WAS THE POPULATION IDENTIFIED? Denmark: Postal questionnaire Random BG, HbA 1c Netherlands: Postal questionnaire Random BG Cambridge: Medical records Random BG, HbA 1c WHO criteria for diabetes Leicester: Practice register OGTT Risk Risk assessment assessment Identification Hyperglycaemia of hyperglycaemi a Diagnosis Diagnosis of diabetes Included 3,057 Target population Invited to be tested Test positive population

INTERVENTION 2001-2009 317 general prac9ce units screened their popula9ons 161 GP units Intensive treatment group 156 GP units Rou9ne Care group Treatment protocol Educa9on Feed back Peer visit Reminders Follow na9onal guidelines

Baseline Follow up Baseline Follow up Baseline Follow Baseline Follow up up Baseline Follow up Baseline Follow up 0 10 % of participants prescribed medication 20 30 40 50 60 70 80 90 BP-lowering Statins Glucose-lowering 100 Routine care Intensive treatment PRESCRIBED TREATMENT AT BASELINE AND 5 YEAR FOLLOW-UP

Griffin et al. Lancet 2011:378:156-67 IT 1678 1654 1622 1564 1348 1058 624 208 RC 1377 1354 1321 1278 1093 879 535 138 Number at risk 0 1 2 3 4 5 6 7 Years of follow-up 0 Primary composite endpoint (%) 2 4 6 8 10 12 p=0.12 14 Routine care Intensive treatment PRIMARY ENDPOINT: CUMULATIVE INCIDENCE OF COMPOSITE CVD ENDPOINT

PRIMARY OUTCOME AT FIVE YEAR: RELATIVE RISK OF COMPOSITE CVD ENDPOINT AS A FIRST EVENT Country Hazard Ratio (95% CI) Denmark 0.83 (0.59 to 1.16) UK 0.80 (0.55 to 1.17) Netherlands 0.96 (0.45 to 2.03) Overall (I-squared = 0.0%) 0.83 (0.65 to 1.05) 0.1 0.2 0.5 1 2 Favours Favours intensive treatment Favours routine care care Griffin et al. Lancet 2011:378:156-67

DANISH REGISTERS

Scan J Pub Health, 2011; 39(Suppl 7): 12 16

DIABETES PREVALENCE IN DENMARK Carstensen B. Diabetologia (2008) 2187-2196

DIABETES INCIDENCE IN DENMARK Carstensen B. Diabetologia (2008) 2187-2196

AGE DISTRIBUTION OF PEOPLE WITH DIABETES IN DENMARK Carstensen B. Diabetologia (2008) 2187-2196

MORTALITY IN PEOPLE WITH DIABETES IN DENMARK Carstensen B. Diabetologia (2008) 2187-2196

MAPPING PATIENT ADHERENCE Jensen ML. Value in Health 17 (2014) 266-274

BRING SUNDHEDSDATA I SPIL DR. ADAM HULMAN AARHUS UNIVERSITY, DEPARTMENT OF PUBLIC HEALTH DANISH DIABETES ACADEMY AARHUS 14-03-2017

EXAMPLES Glucose curves during an oral glucose challenge test (Study 1) Prediction of cardiovascular disease in type 1 diabetes patients (Study 2)

STUDY 1 Diabetes diagnosis is traditionally based on a glucose challenge test Fasting plasma glucose FPG 2-hour post-load glucose (2hPG) (HbA 1c ) Modest overlap between groups diagnosed by different methods Diabetes is a heterogeneous disease What if we have measurements at more than two time points? Can we explain some of the heterogeneity?

STUDY 1 Pooling of available datasets Repeated measurements (n=5-11 per person)

STUDY 1 Data-driven analysis approach Latent class trajectory analysis iden9fies subgroups with similar developmental paderns over 9me Descrip9on of iden9fied classes regarding cardiometabolic risk profiles

STUDY 2 Clinical need Prediction of cardiovascular disease for type 1 diabetes patients Datasets: Steno Diabetes Center (model development) Funen Diabetes Database (external validation) Combined modeling approach Data-driven: random forest, decision tree Conventional: Poisson regression (survival analysis)

Random forest (variable importance) STUDY 2 Decision tree (discover interac9ons)

STUDY 2 Accuracy & calibration

STUDY 2 Poisson regression Needs clinical implementa9on!

steno.dk/t1riskengine

BRING SUNDHEDSDATA I SPIL PROF. DANIEL R. WITTE AARHUS UNIVERSITY, DEPARTMENT OF PUBLIC HEALTH DANISH DIABETES ACADEMY AARHUS 14-03-2017

COST PER GENOME

Nature 2014; 506, 144 145

Nature Immunology 16, 435 439 (2015)

CENTRAL CONSIDERATIONS IN EPIDEMIOLOGY Is an observed association true? What are the alternatives? Chance Bias Selection Information Confounding

TAK FOR OPMÆRKSOMHEDEN! daniel.witte@ph.au.dk