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 Presentation

"Insulin Resistance and the Endothelium - Clinical Manifestations"

Dr. Peter Liu (biography)
English - 2002-11-16 - 33 minutes
(33 slides)

Summary :
Here we will try to shed some light on the relationship between insulin resistance and the cardiovascular disease that we see as a consequence of the process. A current concept is that of endothelial dysfunction: risk factors such as smoking, hypercholesterolemia and diabetes adversely affect the functioning of the endothelium, which leads to buildup of atherosclerotic plaque, plaque rupture and thrombosis, e.g., acute coronary syndrome. The status of endothelial function can be gauged by administering acetylcholine, which will stimulate NO production and cause vasodilatation in normal subjects, but paradoxically cause vasoconstriction in atherosclerotic individuals. These latter patients have a higher risk of proceeding towards a cardiovascular event (Schachinger et al. Circulation. 2000; 101:1902). Patients with diabetes have been showed to have an impaired ability to vasodilate by stimulation with Ach (Williams SB et al. 1996; JACC 27: 567-74). Vasodilatation is also impaired by infusing FFAs (Steinberg et al. 1997; JCI 100:1230), and insulin’s role as a vasodilator is impaired in insulin resistant individuals (Baron AD. 2002. J Diabetes Complications; 16: 92-102). High blood glucose is associated with a significant increase in free radical load (Cosentino F et al. 1997. Circulation; 96: 25-28). Under the influence of glucose and of inflammation (AII), free radicals act to produce potent vasoconstrictors by combining with NO (Laursen. 1997. Circ; 95: 588-593). CRP is now known to be a good integrated factor for looking at inflammation and predicting cardiovascular events (Ridker et al. 2002. NEJM; 347: 1557-65). CRP also tracks well with insulin sensitivity, BMI and hypertension (Festa et al. 2000. Circ; 102: 42). New research by Verma shows the role of CRP in upsetting the balance between vasodilatation and vasoconstriction. So here we have seen that insulin resistance is associated with endothelial dysfunction, and this leads to cardiovascular events through the combination of metabolic abnormalities, oxidative stress and inflammation. The key to therapy is to treat the underlying factors causing insulin resistance, e.g., promoting exercise and weight loss, and using agents such as TZDs, which besides treating insulin resistance are also known to decrease inflammatory markers and LDL oxidation, and improve endothelial function.

More information is available about C-Reactive Protein.

Learning objectives :
The participant will learn about the underlying mechanisms whereby insulin resistance is associated with endothelial dysfunction leading to CAD:

- Insulin resistance associated with endothelial dysfunction leads to CAD via metabolic stress, oxidative stress and inflammation.
- The key to therapy is to correct underlying factors causing insulin resistance by:
o Exercise and weightloss
o Using agents such as TZDs which not only treat insulin resistance but also decrease inflammatory markers and LDL oxidation, and improve endothelial function


Bibliographic references :
Blake GJ, Ridker PM. 2003. C-reactive protein and other inflammatory risk markers in acute coronary syndromes. J Am Coll Cardiol 2003 Feb 19;41(4 Suppl S):S37-42
http://www.ncbi.nlm.nih.gov


   


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