1. Cardiovascular Disease & Mortality in Diabetes Stephen Fava MD, MRCP(UK), FEFIM, FACP, FRCP (Lond), MPhil (Malta), PhD (Exeter) Consultant Physician, Diabetologist & Endocrinologist Head of Diabetes & Endocrine Centre, Mater Dei Hospital, Malta Mater Dei Hospital, Malta

2. Huxley, R. et al. BMJ 2006;332:73-78 Overall summary estimates of relative risks and 95% confidence intervals for fatal coronary heart disease in men and women with and without diabetes in 22 studies that reported both age and multiple adjusted coefficients

3. Glycaemia and Mortality Kaplan-Meier survival curves according to quartiles of HBA1c log rank test P < 0.0001 Menon V et al. Glycosylated hemoglobin and mortality in patients with nondiabetic chronic kidney disease. J Am Soc Nephrol. 2005 Nov;16(11):3411-7

5. Isolated post-challenge hyperglycaemia and mortality 0.7 0.8 0.9 1.0 Cumulative survival (males) 0 2000 4000 10003000 Time (days) Normal Isolated fasting hyperglycaemia Combined fasting / postprandial hyperglycaemia Isolated postprandial hyperglycaemia Known DM Shaw JE et al. Diabetologia 1999;42:1050 Pooled data from 3 population-based longitudinal studies (in Mauritius, Fiji and Nauru)

6. 196 T2 diabetic subjects and 196 age- & sex- matched non-diabetic controls with AMI were recruited Patients with IGT were excluded Biochemical & clinical parameters were measured at baseline & during hospital stay Outcome Of AMI in Diabetes (Fava S et al, Diabetes Care 16:1615-8, 1993)

7. Outcome Of AMI 3-month mortality p<0.05 (Fava S et al, Diabetes Care 16:1615-8, 1993)

8. p< 0.001 p< 0.05

9. Loss of ‘R’ to ‘R’ variability and Mortality p<0.05 (Fava S et al, Diabetes Care 16:1615-8, 1993)

10. Loss of ‘R’ to ‘R’ variability and LVF p<0.02 (Fava S et al, Diabetes Care 16:1615-8, 1993)

11. Thrombolysis p<0.05

14. Mortality after AMI: Recent Data Murcia AM et al: Impact of Diabetes on Mortality in Patients With Myocardial Infarction and Left Ventricular Dysfunction. Arch Intern Med. 2004;164:2273-2279.

15. Outcome Of Unstable Angina p=0.014 p=0.029 Fava S et al, Diabet Med, 14:209-213, 1997

16. Drug Rx After Unstable Angina NitratesCCBAspirin β- Blockers Fava S et al, Diabet Med, 14:209-213, 1997 NS p=0.008

17. Invasive Procedures at 1 year After Unstable Angina p= 0.04 NS p= 0.002 Fava S et al, Diabet Med, 14:209-213, 1997

18. Impact of Albuminuria Gerstein HC et al: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001 Jul 25;286(4):421-6

19. Log-rank test p = 0.008 Kaplan-Meier survival plot Parents of patients with T1 DM with nephropathy Parents of with T1 DM without nephropathy Tarnow L et al, Diabetes Care 23 :30–33, 2000

20. SURVIVAL IN DIABETIC NEPHROPATHY AND ACE GENOTYPE Fava S et al, Diabetes Care 24:2115-20, 2001 p<0.05

21. Circadian Variation in Onset of AMI χ 2 = 13.9, P < 0.005 χ 2 = 1.66, NS Non-diabetic subjectsDiabetic subjects Fava S et al, Heart 1995;74;370-372

22. Circadian Variation in Onset of AMI Rana JS et al: Circadian Variation in the Onset of Myocardial Infarction. Effect of Duration of Diabetes. Diabetes 52:1464-1468, 2003

23. Circadian Variation in Onset of Acute Pulmonary Oedema χ 2 = 9.38, P < 0.005 χ 2 = 0.34, NS Fava S & Azzopardi J. Am J Cardiol 1997 APE AMI

24. Plasma Glucose in Diabetic Patients with AMI Fava S et al: The prognostic significance of Blood Glucose in Diabetic Patients with Acute Myocardial Infarction. Diabetic Med, 1996:13: 80-83 r = 0.92, p< 0.04

25. Malmberg, K. BMJ 1997;314:1512 Actuarial mortality curves during long term follow up in patients receiving insulin-glucose infusion and in control group among total DIGAMI cohort. Absolute risk reduction was 11% DIGAMI RR 0.72 (0.55 to 0.92), p=0.011

26. Conclusions (1) Diabetes is associated with increased mortality after AMI and unstable angina Loss of ‘R’ to ‘R’ variability and  PG on admission are associated with increased mortality in diabetic patients with AMI Outcome after AMI may be improved with tight glycaemic control in the acute stage Mater Dei Hospital, Malta

27. Conclusions (2) Diabetic patients with ACS should be managed aggressively to lower this risk Diabetic patients with renal disease are at a particularly  risk; this is probably partly genetically mediated There is loss of circadian rhythm in the onset of AMI & APE in diabetic patients~ ? implications for chronopharmacology Mater Dei Hospital, Malta