Metabolomics study of the effect of glucocorticoid blockade in patients with type 2 diabetes Academic Essay

Study done on 8 patients with type 2 diabetes, double blind cross over study, the patients blindly given either placebo or glucocorticoid blockade treatment then insulin injected to them to examine the effect of insulin after the glucocorticoid treatment compared to placebo. Plasma samples collected and analysed using metabolomics to examine these effects.
General outlines
1-link between glucocorticoids and insulin resistance (physiologically and pathophysiologically)
2- Glucocorticoid blockade as treatment strategy and its pros and cons compared to conventional treatments.
3-glucocorticoid blockade using glucocorticoid receptor antagonist RU38486 (mifepristone), in combination with a cortisol biosynthesis inhibitor (metyrapone).
4- biochemical perturbations (amino acids, lipids, carbohydrates) affected by insulin resistance (helpful paper: Diabetes – the Role of Metabolomics in the Discovery of New Mechanisms and Novel Biomarkers, Warwick B Dunn), and which affected by glucocorticoids.

Useful references

1. Marchesini G., Brizi M., Bianchi G. et al. Nonalcoholic fatty liver disease; a feature of the metabolic syndrome. Diabetes 2001; 50:1844-1850.
2. Bugianesi E., Gastaldelli A., Vanni E. et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 2005; 48:634-642.
3. Fabbrini E., Mohammed B.S., Magkos F., Korenblat K.M

., Patterson B.W., Klein S. Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease. Gastroenterology 2008; 134:424-431.
4. Donnelly K.L., Smith C.I., Schwarzenberg S.J., Jessurun J., Boldt M.D., Parks E.J. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115:1343-1351.
5. Gastaldelli A., Cusi K., Pettiti M. et al. Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology 2007; 133:496-506.

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