Diabete e danno vascolare: il nesso fisiopatologico comune tra micro e macroangiopatia Gabriele Riccardi Chair of Endocrinology and Metabolic Diseases, Federico II University, Naples, Italy

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Retinopathy predicts cardiovascular events in type 2 diabetes Rosenson RS et al, Atherosclerosis 2011

Multivariate-adjusted hazard ratio of CV events, renal events, all-cause mortality and composite events in Type 2 Diabetes in relation to preexisting microangiopathy P.C.Y. Tong, Diabetic Medicine 2007

Fattori di rischio per lo sviluppo delle complicanze croniche Fattori genetici Compenso glicemico insoddisfacente Durata del diabete Dislipidemia Ipertensione arteriosa Fumo di sigaretta Sovrappeso Sedentarietà Infiammazione subclinica 6

Prognostic value of the Metabolic Syndrome in diabetic patients THE METASCREEN WRITING COMMITTEE* Diabetes Care, 2006

UKPDS: Effect of Tight BP vs Tight Glucose Control on CV Events Any Diabetes End Point Microvascular Outcomes Stroke Death -10 -20 % Reduction p< 0.05 -30 p< 0.05 -40 p< 0.05 p< 0.05 -50 Tight glucose control (FPG <6 mmol/L) Tight BP control (BP <150/85 mm Hg) UKPDS Group, BMJ 1998

Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DIAS). Ansquer JC et al, Am J Kidney Dis 2005

Insulin-resistance Lifestyle - Genetics Hyperinsulinemia Proposed mechanisms linking insulin-resistance and/or hyperinsulinemia with atherosclerosis Insulin-resistance Platelet aggregation HDL-Col Small LDL Post prandial Triglyceride NO Glycemia Lifestyle - Genetics arterial wall Muscle cell proliferation SNS PAI-1 O+ Hyperinsulinemia

General features of the hyperglycaemia induced tissue damage WV Brown, Am J Cardiol 2008

ALTERAZIONI DELLA FUNZIONE ENDOTELIALE INDOTTE DALL’IPERGLICEMIA Adesione Leucociti Citochine Chemochine AGEs PCK ROS Ossido Nitrico Vasodilatazione Proliferazione Migrazione ALTERAZIONI DELLA FUNZIONE ENDOTELIALE INDOTTE DALL’IPERGLICEMIA

Incidence of complications in patients with type 2 diabetes by HbA1c- UKPDS observational study BMJ 2000

Adjusted hazard ratios (HR) for all-cause mortality by HbA1c deciles in people given oral hypoglycemic treatment Currie CJ et al, Lancet 2010

N Engl J Med 2008;358:2545-59

THE ACCORD STUDY INTENSIVE STANDARD Achieved median A1C (%) 6.4 7.5 Weight changes (kg) +3.5 +0.4 Severe hypos (%) 16.2 5.1 On TZD at study end (%) 91 58 On insulin at study 77 55

M= media, T= thrombus, LC=lipid core, FC= fibrous cap an aortic complicated atheromatous lesion with rupture of its fibreous cap M= media, T= thrombus, LC=lipid core, FC= fibrous cap