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COMPLICANZE. CAUSE DI MORTE NEGLI U.S.A. 0 100 200 300 400 Uso di droghe Incidenti stradali Armi da fuoco AlcoolInfezioniObesitàFumo Morti / anno (migliaia)

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Presentazione sul tema: "COMPLICANZE. CAUSE DI MORTE NEGLI U.S.A. 0 100 200 300 400 Uso di droghe Incidenti stradali Armi da fuoco AlcoolInfezioniObesitàFumo Morti / anno (migliaia)"— Transcript della presentazione:

1 COMPLICANZE

2 CAUSE DI MORTE NEGLI U.S.A Uso di droghe Incidenti stradali Armi da fuoco AlcoolInfezioniObesitàFumo Morti / anno (migliaia) McGinnis et al, JAMA, 1993

3 ,0 0,5 1,0 1,5 2,0 2,5 Mortalità Rischio relativo BMI Molto basso Basso Moderato Alto Molto alto RELAZIONE TRA MORTALITÀ E BMI Bray, Clin Endocrinol Metab, 1999

4 BMI Type 2 Diabetes Hypertension Cholelithiasis Coronary heart disease RELATIONSHIP BETWEEN BMI AND THE RELATIVE RISK OF: Willet et al, N Engl J Med, 1999 Realative risk

5 Body Mass Index - B M I (Kg/m 2 ) International Obesity Task Force < 18.5= Sottopeso = Normopeso = Sovrappeso = Obesità classe I = Obesità classe II > 40= Obesità classe III

6 RR Diabete tipo 2 Decili Circonferenza vita BMI Wang et al, Am J Clin Nutr, 81: , 2005 RELAZIONE TRA DECILI DI CIRONFERENZA VITA E BMI E RISCHIO RELATIVO DI DIABETE TIPO 2

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10 Sindrome Metabolica: Insulino-resistenza, diabete, dislipidemia, ipertensione; Malattie cardiovascolari Neoplasie Colelitiasi Artrosi Disordini psico-sociali Apparato respiratorio: Insufficienza restrittiva (grandi obesi); Apnee notturne (potenziale grave ipossia). MORBILITÀ NELLOBESITÀ

11 OBESITÀ E RISCHIO CARDIOVASCOLARE Cause dirette Ipertrofia ventricolo sn. Morte improvvisa Ipertensione Cause indirette Sindrome Metabolica: Insulino-resistenza, diabete, dislipidemia, ipertensione;

12 CAUSE DIRETTE Ipertrofia del ventricolo sinistro - Volemia (sodio-ritenzione, attivaz. simpatica, PRA) - Gittata sistolica - Postcarico Morte improvvisa - Aritmie (Ipertrofia ventr sin; dilataz. atrio sin; infiltrazione grassa del sistema di conduzione) - Q-T - Apnee notturne

13 CAUSE INDIRETTE Sn. Metabolica (oppure Sn. da insulino-resistenza o Sn. X) Insulino-resistenza Iperinsulinemia Diabete tipo 2 o IGT o IFG Ipertensione HDL Trigliceridi Apo B LDL piccole e dense Fibrinogeno PAI-1 IL-6 e PCR Disfunzione endoteliale

14 G.B. Morgagni Around 1750, Joannes Baptista Morgagni clearly described increased intraabdominal and mediastinal fat accumulation in android obesity. Remarkably, he also recognized the association between visceral obesity, hypertension, hyperuricemia, atherosclerosis, and obstructive sleep apnea syndrome.

15 In 1947, Jean Vague rediscovered the importance of the android obesity phenotype and its association with diabetes, atherosclerosis, gout, and uric-acid calculous disease. Vague J. La différenciacion sexuelle, facteur déterminant des formes de l'obésité. Presse Med;30:339-40, 1947 Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr.;4:20–34, 1956

16 Overweight, Obesity, and Mortality in a Large Prospective Cohort of Persons 50 to 71 Years Old Adams et al, NEJM, , aa, 10 yrs

17 ASSOCIATION OF GENERAL AND ABDOMINAL OBESITY WITH MULTIPLE HEALTH OUTCOMES IN OLDER WOMAN The IOWA Womans Health Study Folsom AF et al, Arch Internal Med, 2000 Uterine Cancer aa

18 RR Diabete tipo 2 Decili Circonferenza vita BMI Wang et al, Am J Clin Nutr, 81: , 2005 RELAZIONE TRA DECILI DI CIRONFERENZA VITA E BMI E RISCHIO RELATIVO DI DIABETE TIPO 2

19 INTERNATIONAL DAY FOR THE EVALUATION OF ABDOMINAL OBESITY (IDEA) A Study of Waist Circumference, Cardiovascular Disease, and Diabetes Mellitus in Primary Care Patients in 63 Countries Balkau B et al, Circulation, 2007 Frequency (%) Waist Circunference (cm) Frequency (%) CVD DIABETES

20 LOWER-BODY ADIPOSITY AND METABOLIC PROTECTION IN POSTMENOPAUSAL WOMEN Leg Fat Visceral Fat Triglycerides (mg/dl) Van Pelt et al, J Clin Endocrinol Metab, 90:4573–4578, 2005

21 Low sc thigh fat is a risk factor for unfavourable glucose and lipid levels The Health ABC Study Fasting glucose (mmol/l) Snijder et al, Diabetologia, 2005 Visceral Fat tertiles 3.000, aa SC thigh Fat tertiles

22 BMI Rapporto Vita/Fianchi Prevalenza CHD % PREVALENZA DI RISCHIO 10-y-CHD > 15% PER CLASSI DI BMI E WHR: HEALTH SURVEY FOR ENGLAND Nanchahal et al, Int J Obes 29:317,

23 Obesity and the risk of MI in participants from 52 countries: a case-control study INTERHEART study Yusuf S et al, Lancet, 366: , 2005 AMI BMI quintiles Waist-to-hip quintiles

24 Obesity and the risk of MI in participants from 52 countries: a case-control study INTERHEART study Yusuf S et al, Lancet, 366: , 2005 AMI Waist quintiles Hip quintiles

25 Bellia et al, Diabetes (ADA) 2004 STUDIO LINOSA: (364, > 18 aa) Ford ES, Diabetes Care 2005 PREVALENZA DI OBESITÀ ADDOMINALE NELLA S. METABOLICA (NCEP) NHANES 1999–2002 (3.601, > 20 aa) SM NCEP 21.4%

26 DISTRIBUZIONE DEI DEPOSITI DI GRASSO periferica, ginoide centripeta, androide

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28 VISCERAL vs SUBCUTANEOUS FAT insulin antilipolytic effect. expression of cortiocosteroids receptors. DEX-induced LPL stimulation. expression of androgen receptors. High FFA portal flux increases hepatic glucose production and VLDL synthesis. cathecolamines lipolytic effect. TZD effects on preadipocytes.

29 Energy Homeostasis Leptin Adiponectin Resistin Visfatin 1 Glicop. SAA3 PTX Innate Immune System TNF IL-6 Acute Phase Reactant Response VEGF Angiotensin II Vascular Remodeling LPL HSL Lipoprotein Metabolism Fibrinolysis PAI-1 PREADIPOCYTE ADIPOCYTE

30 Adiponectin in IAA Anti-atherogenic/antidiabetic: foam cells vascular remodelling insulin sensitivity hepatic glucose output IL-6 in IAA Pro-atherogenic/pro-diabetic: vascular inflammation insulin signalling TNF in IAA Pro-atherogenic/pro-diabetic: insulin sensitivity in adipocytes (paracrine) PAI-1 in IAA Pro-atherogenic: atherothrombotic risk Properties of key adipokines IAA: intra-abdominal adiposity Marette 2002

31 Adipokine PAI-1 IL-6 Leptin Adiponectin TNF- Angiotensinogen Resistin Visceral Adip Tissue (VAT) Vs Subcutaneous Adip Tissue (SAT) VAT> SAT SAT > VAT ? VAT > SAT ?

32 Einstein FH et al: Diabetes 54:672, SCvisc SCvisc SCvisc SCvisc SCvisc SCvisc SCvisc SCvisc. resistinaleptinaangiot.-genoadiponectina PAI-1IL-6IL-10TNF-a digiuno iperglicemia iperinsulinemia viscerale e sottocutaneo rispondono in modo diverso (espressione di geni)

33 INS. RES.

34 Gabriely et al, Diabetes, 51: , 2002 Removal of Visceral Fat Prevents Insulin Resistance of Aging M (mg/kg/min) HGP (mg/kg/min) * * ?

35 PrimaDopo 36% EFFETTI DELLA RIMOZIONE DI TESSUTO ADIPOSO SOTTOCUTANEO MEDIANTE LIPOSUZIONE Nessun effetto su: Sensibilità insulinica Pressione arteriosa Glicemia Colesterolo tot. E HDL Trigliceridi FFA Leptina Adiponectina TNFα IL-6 PCR Klein et al, N Engl J Med, 350: , 2004

36 Mandibuloacral dysplasia LIPODISTROFIE PARZIALI Sbraccia et al, Diabetes (ADA) 2004 WP NORMALE BMI: 21.2 Circ. vita: 91 cm Massa grassa: 24.8% AF BMI: 14.3 Circ. vita: 68 cm Massa grassa: 15.4%

37 lipotoxicity: too fat in the wrong tissue atherosclerosisinsulin-resist.steatosisdiabetes spill-over

38 Cree MG et al.: J Clin Endocrinol Metab 89:3864, giovanianziani giovanianziani u.a. TG nel muscolo TG nel fegato il deposito di trigliceridi determina insulino-resistenza

39 Insulin Resistance And Adiposity Correlate With Acute- phase Reaction and Soluble Cell Adhesion Molecules in Type 2 Diabetes. Leinonen E et al, Atherosclerosis 166:387–394, 2003 NIDDM as a Disease of the Innate Immune System: Association of Acute-phase Reactants and Interleukin-6 with Metabolic Syndrome X. Pickup JC et al, Diabetologia 40:1286 –1292, 1997 INFIAMMAZIONE E DIABETE TIPO 2

40 INFIAMMAZIONE E DT2: STUDI PROSPETTICI High White Blood Cell Count is Associated With a Worsening of Insulin Sensitivity and Predicts the Development of Type 2 Diabetes. Vozarova B et al, Diabetes 51:455– 461, 2002 The Relation of Markers Of Inflammation To The Development of Glucose Disorders in the Elderly: The Cardiovascular Health Study. Barzilay JI et al, Diabetes 50:2384 –2389, 2001 Low-grade Systemic Inflammation and the Development of Type 2 Diabetes: The Atherosclerosis Risk In Communities Study. Duncan BB et al, Diabetes 52:1799 –1805, 2003

41 BMI Markers Infiammatori PCR IL-6 Fibrinogeno 1-glicoproteina acida Kern et al, Am J Physiol Endocrinol Metab Cottam et al, Obes Surg Yudkin et al, Atherosclerosis Berg & Sherer, Circulation 2005

42 Impact of Weight Loss on Inflammatory Proteins and Their Association With the Insulin Resistance Syndrome in Morbidly Obese Patients Kopp et al, Arterioscler Thromb Vasc Biol.2003 CRPIL-6 TNF

43 CRP Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance The Diabetes Prevention Program Research Group Diabetes 2005

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46 Xu et al, J Clin Invest 2003 Weisberg et al, J Clin Invest 2003

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