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1 BRING SUNDHEDSDATA I SPIL PROF. DANIEL R. WITTE AARHUS UNIVERSITY, DEPARTMENT OF PUBLIC HEALTH DANISH DIABETES ACADEMY AARHUS
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3 GLUCOSE, INSULIN AND THE PANCREAS
4 THE MAIN COMPLICATIONS OF DIABETES Re9nopathy Coronary Heart Disease Cerebrovascular Disease Nephropathy Neuropathy Peripheral Vascular Disease
5 DIABETES SUBTYPES (2014) Groop & Pociot. Mol Cell Endocrinol Jan 25;382(1):726-39
6 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
7 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
8 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
9 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 In a more personalised way
10 CENTRAL CONSIDERATIONS IN EPIDEMIOLOGY Is an observed association true? What are the alternatives? Chance Bias Selection Information Confounding
11 THE WHITEHALL II STUDY British observational, occupational cohort study 10,308 participants years old Men (70%) and women (30%) Started in years of follow-up with OGTT ( ) 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
12 Window of opportunity for preven9on Tabák AG, Lancet Jun 27;373(9682): Tabák AG, Lancet Jun 16;379(9833):
13 FINDING DIABETES PATIENTS IN THE GENERAL POPULATION General Population High Risk Population Patients with undiagnosed diabetes Patients with known diabetes
14 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 NCT
15 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
16 INTERVENTION 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
17 Baseline Follow up Baseline Follow up Baseline Follow Baseline Follow up up Baseline Follow up Baseline Follow up 0 10 % of participants prescribed medication BP-lowering Statins Glucose-lowering 100 Routine care Intensive treatment PRESCRIBED TREATMENT AT BASELINE AND 5 YEAR FOLLOW-UP
18 Griffin et al. Lancet 2011:378: IT RC Number at risk Years of follow-up 0 Primary composite endpoint (%) p= Routine care Intensive treatment PRIMARY ENDPOINT: CUMULATIVE INCIDENCE OF COMPOSITE CVD ENDPOINT
19 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) Favours Favours intensive treatment Favours routine care care Griffin et al. Lancet 2011:378:156-67
20 DANISH REGISTERS
21 Scan J Pub Health, 2011; 39(Suppl 7): 12 16
22 Scan J Pub Health, 2011; 39(Suppl 7): 12 16
23 DIABETES PREVALENCE IN DENMARK Carstensen B. Diabetologia (2008)
24 DIABETES INCIDENCE IN DENMARK Carstensen B. Diabetologia (2008)
25 AGE DISTRIBUTION OF PEOPLE WITH DIABETES IN DENMARK Carstensen B. Diabetologia (2008)
26 MORTALITY IN PEOPLE WITH DIABETES IN DENMARK Carstensen B. Diabetologia (2008)
27 MAPPING PATIENT ADHERENCE Jensen ML. Value in Health 17 (2014)
28 MAPPING PATIENT ADHERENCE Jensen ML. Value in Health 17 (2014)
29 MAPPING PATIENT ADHERENCE Jensen ML. Value in Health 17 (2014)
30 BRING SUNDHEDSDATA I SPIL DR. ADAM HULMAN AARHUS UNIVERSITY, DEPARTMENT OF PUBLIC HEALTH DANISH DIABETES ACADEMY AARHUS
31 EXAMPLES Glucose curves during an oral glucose challenge test (Study 1) Prediction of cardiovascular disease in type 1 diabetes patients (Study 2)
32 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?
33 STUDY 1 Pooling of available datasets Repeated measurements (n=5-11 per person)
34 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
35 READ MORE:
36 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)
37 Random forest (variable importance) STUDY 2 Decision tree (discover interac9ons)
38 STUDY 2 Accuracy & calibration
39 STUDY 2 Poisson regression Needs clinical implementa9on!
40 steno.dk/t1riskengine
41 READ MORE:
42 BRING SUNDHEDSDATA I SPIL PROF. DANIEL R. WITTE AARHUS UNIVERSITY, DEPARTMENT OF PUBLIC HEALTH DANISH DIABETES ACADEMY AARHUS
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45 COST PER GENOME
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47 Nature 2014; 506,
48 Nature Immunology 16, (2015)
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62 CENTRAL CONSIDERATIONS IN EPIDEMIOLOGY Is an observed association true? What are the alternatives? Chance Bias Selection Information Confounding
63 TAK FOR OPMÆRKSOMHEDEN!
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