Hypertension and Diabetes: Role of the Renin-Angiotensin System

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Over the past decade there have been a large number of well-designed studies addressing the role of antihypertensive therapy in diabetic populations on a range of micro- and macrovascular endpoints. The evidence that certain antihypertensive agents such as drugs that interrupt the RAS are superior in terms of renal protection is now very convincing. We await with great anticipation the imminent findings from the DIRECT study [4,93] as to the role of RAS blockade in the prevention and retardation of diabetic retinopathy. The effects of antihypertensive treatments on macrovascular disease, left ventricular hypertrophy, and heart failure continue to be clearly shown in the diabetic population but the superiority of one class of drugs over another has not been fully elucidated. Ongoing studies such as ONTARGET [50] and the Action in Diabetes and Vascular Disease study (ADVANCE) [60] should extend our understanding as to what the target blood pressure should be in the diabetic patient and which combinations are the best not only in terms of end-organ protection but also on glucose and lipid metabolism. Indeed, one of the most exciting aspects of potential benefits of RAS blockade relates to the increasingly appreciated effects with both ACE inhibitors and ARBs on prevention and retardation of the development of type 2 diabetes. Current ongoing clinical trials will greatly assist in confirming this potential benefit although the mechanisms responsible for this metabolic advantage of such agents remain to be fully delineated. Finally, the recent identification of new components of the RAS such as the enzyme ACE2 and the putative renin receptor and the increased interest in aldosterone antagonists should provide fertile territory to not only examine new targets linked to the RAAS but potentially to design more rational treatments. These therapies aim not only to reduce diabetes-related end-organ complications, often exacerbated by hypertension, but also to attenuate or retard the progression of the insulin-resistance syndrome in which diabetes and hypertension are such important clinical manifestations.

Original languageEnglish
Pages (from-to)469-490
Number of pages22
JournalEndocrinology and Metabolism Clinics of North America
Issue number3
Publication statusPublished - 1 Sep 2006
Externally publishedYes

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