DIABETE MELLITO Complicanze microvascolari Complicanze macrovascolari " Aterosclerosi " Cardiomiopatia diabetica " Nefropatia diabetica " Retinopatia diabetica " Neuropatia diabetica
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DIABETE MELLITO
Complicanzemicrovascolari
Complicanzemacrovascolari
• Aterosclerosi
• Cardiomiopatia diabetica
• Nefropatia diabetica
• Retinopatia diabetica
• Neuropatia diabetica
NEFROPATIADIABETICA
NEFROPATIA DIABETICA
Alterazione della funzionerenale causata dal diabete edefinita clinicamente dallapresenza di proteinuriapersistente, in assenza diinfezioni delle vie urinarie, dialtre malattie renali o discompenso cardiaco.
GLOMERULO RENALE
IPERTROFIAGLOMERULARE
MODIFICATAPOROSITA’
M. B. G.
PRESSIONETRANSCAPILLARE
INTRAGLOMERULARE
DISTACCOCELLULE
EPITELIALIVISCERALI
ALTERAZIONE DELLA PERMEABILITÀGLOMERULARE ALL’ALBUMINA
ALTERAZIONEDELLO “SLIT-
PORE”
ALTERAZIONECARICHE
ELETTRICHE
Hemodynamic pathwayBlood flow/Pressure
Vasoactive factors(AII, ET, vasopressin, natriureticpeptides, NO, prostaglandins)
Metabolic pathwayGlucose
Polyols AGEs Glucosetransporters
Intracellular secondmessengers
(PKC NF-kB MAPK)
Growth factorsand Cytokines
(TGF-beta, CTGF, VEGF, PDGF, GH/IGF, EGF)
Aumento matrice extracellulare, Glomerulosclerosi, Fibrosi interstiziale,Albuminuria
Cooper ME, Lancet, 352, 1998
ADVANCED GLYCOSYLATIONENDPRODUCTS (AGEs)
HYPERGLYCAEMIA
NF-k B
DIABETIC COMPLICATIONS
R1
TGF-beta
Extracellular matrix
AGEs
MSR R2 R3 RAGE
clearance
AGEcross-links
PKC
cytokines
? ?
Espressione glomerulare dell’ACEnel diabete
Controlli Diabetici Diabetici + ACEI
mesangial cell
monocyte
macrophagefibroblasts
glomerularcapillary
extracellularmatrix
Ang IIAng II
TGF1bFGFPDGF
endothelin
Direct and indirect renal effects of angiotensinDirect and indirect renal effects of angiotensin
Glomerulus
Ang I
Johnston & Risvanis
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