ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus

ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus.BackgroundThe enormous contribution of renin-angiotensin system (RAS) interruption with ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers (ARB) in the treatment of diabetic nephropathy has led to interest in the factors involved in angiotensin II (Ang II) generation. In normal subjects, RAS interruption using an ARB produced a 50% greater renal plasma flow (RPF) rise than with an ACE inhibitor, suggesting a substantial contribution of non-ACE pathways. Moreover, immunohistochemistry studies in kidneys of overtly proteinuric diabetic subjects showed up-regulation of chymase, an alternative Ang II-generating enzyme. Our aim was to determine the degree to which the non-ACE pathways contribute to RAS activation in type 1 diabetes mellitus (DM).MethodsType 1DM patients (N = 37, 14 M/23 F; age 31 ± 2 years; DM duration 16 ± 1.7 years; HbA1c 7.7.0 ± 0.3%) were studied on a high-salt diet. They received captopril 25mg po one day and candesartan 16mg po the next day. RPF and glomerular filtration rate (GFR) were measured before and up to 4 hours after drug administration.ResultsBoth captopril and candesartan induced a significant rise in RPF (baseline vs. peak <0.0001 for both), and the rise was concordant for the 2 drugs (r = 0.77,P < 0.001). However, the RPF responses were not significantly different between the 2 drugs (captopril 72 ± 11mL/min/1.73m2, candesartan 75 ± 12,P = 0.841).ConclusionIn predominantly normoalbuminuric, normotensive type 1 DM, activation of the intrarenal RAS reflects a mechanism involving primarily the classic ACE pathway

Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association

Type 1 diabetes is characterized by an immune-mediated depletion of β-cells that results in lifelong dependence on exogenous insulin. While both type 1 and type 2 diabetes result in hyperglycemia, the pathophysiology and etiology of the diseases are distinct and require us to consider each type of diabetes independently. As such, this position statement summarizes available data specific to the comprehensive care of individuals with type 1 diabetes. The goal is to enhance our ability to recognize and manage type 1 diabetes, to prevent its associated complications, and to eventually cure and prevent this disease. The exact number of individuals with type 1 diabetes around the world is not known, but in the U.S., there are estimated to be up to 3 million (1). Although it has long been called “juvenile diabetes” due to the more frequent and relatively straightforward diagnosis in children, the majority of individuals with type 1 diabetes are adults. Most children are referred and treated in tertiary centers, where clinical data are more readily captured. The SEARCH for Diabetes in Youth study estimated that, in 2009, 18,436 U.S. youth were newly diagnosed with type 1 diabetes (12,945 non-Hispanic white, 3,098 Hispanic, 2,070 non-Hispanic black, 276 Asian-Pacific Islander, and 47 American Indian) (2). Worldwide, ∼78,000 youth are diagnosed with type 1 diabetes annually. Incidence varies tremendously among countries: East Asians and American Indians have the lowest incidence rates (0.1–8 per 100,000/year) as compared with the Finnish who have the highest rates (>64.2 per 100,000/year) (3). In the U.S., the number of youth with type 1 diabetes was estimated to be 166,984 (4). The precise incidence of new-onset type 1 diabetes in those over 20 years of age is unknown. This may be due to the prolonged phase of onset and the subtleties in distinguishing the different