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
Riccardi G et al, ATVB 1988
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
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
Stroke
Any Diabetes
End Point
Microvascular
Outcomes
Death
0
% Reduction
-10
-20
p< 0.05
-30
p< 0.05
-40
-50
p< 0.05
p< 0.05
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
Proposed mechanisms linking insulin-resistance and/or
hyperinsulinemia with atherosclerosis
Insulin-resistance
Lifestyle - Genetics
Platelet
aggregation
NO
Glycemia
HDL-Col
Small LDL
Post
prandial
Triglyceride
arterial wall
Muscle cell
proliferation
O+
SNS
Hyperinsulinemia
PAI-1
General features of the hyperglycaemia induced tissue damage
WV Brown, Am J Cardiol 2008
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
Incidence / 1000 / year
70
MI (fatal + non fatal)
Microvascular disease
60
50
40
30
20
10
0
<6
6 to 7
7 to 8
8 to 9
HbA1c %
9 to 10
>10
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
end (%)
55
an aortic complicated atheromatous lesion with
rupture of its fibreous cap
M= media, T= thrombus, LC=lipid