替米沙坦与代谢综合征

TG, HDL-C sd LDL-C Hypertension Uric Acid PAI-1
Impaired Glucose Tolerane
Type 2 Diabetes
Endothelial Dysfunction
Inflammation Thrombosis Oxidation
Hsueh WA, Law R. AJC, 2003
Insulin-mediated
Skeletal muscle
glucose uptake
CAD, Stroke, Peripheral vascular disease
Atherosclerosis
Adipose
FFA Inflammatory
Adipokines
Liver
Glucose production
Quinones et al Ann Intern Med., 2004; 140:700-86
Approaches that Improve Coronary Vasomotor Function in Insulin Resistance:
• Insulin sensitizers: TZDs, PPAR ligands • AT1 receptor blockers: ARBs • Glucose control in type 2 diabetes: Metformin
VALUE (Valsartan Antihypertensive Long-Term
Use Evaluation): 23% less new onset diabetes
Atherosclerosis
Atherosclerosis
Unstable plaque Inflammation, Fibrosis Cap
Thrombosis and Rupture
Event
4
Lifetime Risk for Diabetes in the US
For individuals born in 2000: Males – 32.8% Femaleቤተ መጻሕፍቲ ባይዱ – 38.5% Estimated loss of life expectancy if diagnosed at age 40: Males – 11.6 years Females – 14.3 years
Insulin production
Diabetes
Albumin excretion
Diabetic Nephropathy
Diabetic
VEGF
Retinopathy
neovascularization
Diastolic dysfunction, interstitial fibrosis heart failure
Vascular inflammation
endothelial dysfunction
3
Progression of Atherosclerosis in Insulin Resistance
Insulin Resistance
Hyperinsulinemia
Metabolic Syndrome
CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality
and Morbidity): 40% less new onset
diabetes with candesartan in patients with heart failure
Narayan JAMA 2003
5
Noninvasive Measurements of Myocardial Blood Flow: Positron Emission Tomography
Rest
CPT
DIP
0’
25’
45’
70’
90’ 115’
135’
13NH3
13NH3
13NH3
Dipyridamole (0.56 mg/kg)
LIFE (Losartan Intervention for Endpoint
Reduction in Hypertension): 25% less new
onset diabetes with losartan compared to atenolol in patients with hypertension and left ventricular hypertrophy
Cardiomyopathy
2
Adipokines Mediate Insulin Resistance and Inflammation
adiponectin
TNF
angiotensinogen
IL6
leptin FFA
PAI-1
Insulin sensitivity
insulin resistance
7
Inhibition of the Renin-angiotensin System Prevents Diabetes:
HOPE (Heart Outcomes Prevention
Evaluation): 32% less new onset
diabetes with ramipril compared to placebo in high cardiovascular risk patients
Cardiovascular Risk Continuum: Implications of Insulin Resistance and Diabetes
Willa Hsueh, M.D.
Professor of Medicine Chief, Division of Endocrinology, Diabetes, and Hypertension
UCLA David Geffen School of Medicine Los Angeles, California
1
Diabetes is a vascular disease: Angiotensin II has been implicated in both the development of diabetes and its complications