1. The concept of Diabetes & CV risk: A lifetime risk challenge Diabetes & CV Risk: Routine practice versus guidelines Eberhard Standl, MD Professor of Medicine Munich Diabetes Research Group/ Diabetes Research Institute.MD Munich, Germany Cardio Diabetes Master Class European chapter Munich, Germany May 6-8, 2011 Slide lecture prepared and held by: Presentation topic

2. Coronary artery disease (CAD) and diabetes (DM) Main diagnosis DM ± CAD Main diagnosis CAD ± DM CAD unknown ECG, Echocardiography, Exercise test DM known Screening nephropathy If poor glucose control (HbA1c >6.5%) Diabetology consultation DM unknown OGTT Blood lipids & glucose HbA1c If MI or ACS aim for normoglycemia CAD known ECG, Echocardiography, Exercise test Positive finding Cardiology consultation Normal Follow up Abnormal Cardiology consultation Ischemia treatment Noninvasive or invasive Newly detected DM or IGT ± metabolic syndrome Diabetology consultation Normal Follow up New ESC/EASD Guidelines Investigational algorithm

3. Ten important recommendations (1)  To reach (all) treatment targets including those for glycaemic control  To screen for DM and IGT by means of an OGTT in all patients with coronary artery disease and in other high risk individuals  To let life style counselling be the cornerstone in preventing DM and CVD  To offer patients with DM and ACS standard guideline based treatment, early angiography and mechanical revascularisation  To apply strict, when needed insulin based, glucose control in acutely ill DM patients

4. Ten important recommendations (2)  To favour CABG over PCI when revascularising DM patients  To use drug-eluting stents in PCI with stent implantation  To include investigations for cardiac autonomic dysfunction, heart failure, arrhythmias, hypotension, PVD (Doppler-Index), eGFR and (micro) - albuminuria  To use a multifactorial (tight glucose, BP and lipid-control and antiplatelet therapy) approach  To establish a collaboration between cardiologists and diabetologists

5. 110 from 25 countries n= 4 961 2- 6 weeks per centre February 2003 to January 2004 Euro Heart Survey Diabetes and the Heart Participating centres Type of centre: 47% hospital cardiology wards 45% hospital based outpatient clinics 8% outpatient clinics (Bartnik et al Eur Heart J 2004; 25:1880-90)

6. Prescribed glucose lowering drugs 77 (17%) 1% 16% <1% 83% Insulin Oral drugs Combinations No prescription Newly detected diabetes n = 452 Not prescribed glucose lowering drugs 375 (83%) (Anselmino et al Eur Heart J 2008;29:177) Glycemic control Experiences from the Euro Heart Survey Glucose lowering drugs at follow up in patients with newly detected diabetes

7. Euro Heart Survey Diabetes and the Heart Newly detected diabetes: Combined cardiovascular events with or without prescribed pharmacological glucose-lowering treatment Anselmino, Malmberg, Standl, Rydén, EuroHeartJ, (2008) 29:177-184.

8. NGTIFGIGTDM Acute admission n=923 389 (42%) 39 (4%) 294 (32%) 201 (22%) Elective consultation n=997 486 (49%) 50 (5%) 320 (32%) 141 (14%) OGTT (0 min) <6.1  6.1 and <7.0 <7.0  7.0 OGTT (2 h) <7.8  7.8 and <11.1 or  11.1 Patients with coronary artery disease (CAD) and no diabetes (OGTT cohort n=1920) Euro Heart Survey Diabetes and the Heart OGTT outcome Bartnik M et al. Eur Heart J 2004;25:1880–1890.

9. Euro Heart Survey Diabetes and the Heart Fasting and post-load glycaemia in patients with CAD and without previously diagnosed diabetes Fasting glycaemia (mmol/l)Post-load glycaemia (mmol/l) <5.6 5.6-6.1 6.1-7.0 ≥7.0≥11.1 7.8-11.1 <7.8 ( n =1867) Number of patients Dm IGT NGT Bartnik M et al. Heart 2007;93:72–77.

10. CAD: coronary artery disease; OGTT: oral glucose tolerance test; FPG: fasting plasma glucose; IFG: impaired fasting glucose; IGT: impaired glucose tolerance 1. Bartnik M, et al. Eur Heart J 2004;25:1880–90. 2. Hu DY, et al. Eur Heart J 2006;27:2573–9. China Heart Survey 2 (n=3,513) ~3/4 of patients have hyperglycaemia Euro Heart Survey 1 (n=4,961) 2/3 of patients have hyperglycaemia Previously known diabetes Normal glucose tolerance Prediabetes (IGT) Newly diagnosed diabetes 33% 23% 24% 20% 21% Hyperglycaemia is common and often undiagnosed in patients with CAD in Europe and Asia 25% 31% 12% 3% 29% Prediabetes (IFG)

11. Undiagnosed diabetes in the U.S. population aged ≥ 20 years by diagnostic criteria 0.2% 1.0% 1.2% 0.1% 0.3% 2.5% FPG 2.5% A1c 1.6% 2-h glucose 4.9% Cowie CC et al. Diabetes Care 2010

12. International Expert Committee report on the role of the A 1 C assay in the diagnosis of diabetes A1C ≥ 5.7% to < 6,5% high risk for Diabetes A1C ≥ 6,5% undiagnosed diabetes ADA : or FPG > 7.0 mmol/l and/or post load ≥ 11.1 mmol/l Diabetes Care 2009 32: 1327 -1334 WHO position statement 2011: HbA1c > 6.5 diagnostic for DM, levels below do not exclude diagnosis using glucose tests, no formal recommendation to interprete levels < 6.5 %

13. Type 2 Diabetes: some evidence based recommendations in primary CV prevention 2011 Evidence for CHD risk equivalence: controversial, but total risk has decreased, i.e. to 10-15% over 10y in the best case scenario vs some 25% with silent myocardial ischemia Should every diabetic be on low dose aspirin? – probably not (bleeding hazards), however rather limited data base Should every diabetic be on a statin with a LDL target of 70 mg/dl? – probably yes, but more studies warranted Should every diabetic be on anti-RAS therapy? Probably yes, but avoid hypotension, especially with preexisting CVD Silent myocardial ischemia in totally asymptomatic patients with diabetes – is frequent, some 30 %, and with high risk (see above). Appropriate multifactorial therapy plus good medical monitoring for signs and symptoms of CHD effective and economic approach

14. Multifactorial Intervention in type 2 Diabetes Euro Heart Survey Diabetes and the Heart (Anselmino et al Europ J Cardiovasc Prev Rehab 2008;15:216) 0100200300400 0,91 0,92 0,93 0,94 0,95 0,96 0,97 0,98 0,99 1,00 No DM EBM + No DM EBM - DM EBM + DM EBM - Time of follow up (days) Cumulative survival Impact of Evidence Based Medicine (EBM) on 1-year mortality

15. Multifactorial Intervention in type 2 Diabetes Euro Heart Survey Diabetes and the Heart (Anselmino et al Europ J Cardiovasc Prev Rehab 2008;15:216) Treatment type Diabetes NNT to avoid one event Treatment type Diabetes NNT to avoid one event Fatal Cardiovascular Fatal Cardiovascular Evidence BasedNo1826141 MedicineYes2432 RevascularisationNo10541 Yes3414 Evidence Based Medicine Revascularization Number Needed to Treat with EBM and Revascularisation