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Chemical Biology: Approaches to Drug Discovery and Development to Targeting Disease by Natanya Civjan

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Chapter 21: Metabolic Diseases

Cynthia M. Arbeeny

Endocrine and Metabolic Diseases, Genzyme Corporation, Framingham, Massachusetts

Obesity, type 2 diabetes (T2D), lipid disorders, and hypertension are chronic and disabling diseases that afflict hundreds of millions of individuals worldwide. In this chapter, they are collectively referred to as “cardiometabolic diseases,” because they have “common ground:” They increase the risk of cardiovascular disease (CVD) morbidity and mortality. Considerable research has been performed to understand the etiology of cardiometabolic diseases and to translate this research into effective treatment paradigms. However, it has been challenging to understand the initiation and progression of cardiometabolic diseases. This difficulty is attributed to the complexities involved in metabolic regulation, a resultant “snowballing” effect, and a downward spiral as disease progresses. The first line of therapy for treating obesity, T2D, and/or dyslipidemia is lifestyle intervention, which can impact significantly on disease and decrease CV risk, but is usually not effective because of lack of patient compliance. Patients are then given a plethora of drugs to treat the individual risk factors. However, new therapies are critically needed, because most patients require multiple drugs, some drugs may treat one CVD risk factor and exacerbate another, and most patients do not meet treatment goals. A “magic bullet” that treats the underlying causes that contribute ...

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