Endothelial Dysfunction Is Correlated With Microalbuminuria in Children With Short-Duration Type 1 Diabetes

Ladeia, Ana Marice Teixeira; Ladeia-Frota, Carol; Pinho, Luiz; Stefanelli, Eridan; Adan, Luís

doi:10.2337/diacare.28.8.2048

Cited by 38 publications

(30 citation statements)

References 13 publications

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“…However, as microalbuminuria may reflect insulin resistance, which we postulate underlies much of the excess CAD in type 1 diabetic patients, and is an early marker of renal disease, its predictive power may lie in representing not just a risk state but widespread vascular damage, as originally proposed by the Steno Investigators (40). Subsequent analyses (41,42) have reinforced this Steno hypothesis and further stressed the importance of microalbuminuria as a marker of vascular change. Endothelial dysfunction, which has been shown to precede microalbuminuria by 2-3 years (42,43), has been suggested as the possible link to the concomitant development of the renal and cardiovascular complications often seen in type 1 diabetic patients (44,45).…”

Section: Results -Of the 514 Participantsmentioning

confidence: 84%

The Prediction of Major Outcomes of Type 1 Diabetes: a 12-Year Prospective Evaluation of Three Separate Definitions of the Metabolic Syndrome and Their Components and Estimated Glucose Disposal Rate

2007

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OBJECTIVE—The metabolic syndrome has been shown to confer an increased risk of cardiovascular disease in both the general and type 2 diabetic populations, but few studies have assessed the metabolic syndrome in type 1 diabetic patients. In a type 1 diabetic cohort, we assessed the prevalence and value of the metabolic syndrome in improving the prediction of major complication outcomes compared with its components and a surrogate measure of insulin resistance, estimated glucose disposal rate (eGDR). RESEARCH DESIGN AND METHODS—A total of 514 (78%) subjects participating in the Pittsburgh Epidemiology of Diabetes Complications Study with complete 12-year follow-up clinical data were classified by baseline metabolic syndrome status according to three definitions: those of the National Cholesterol Education Program Adult Treatment Panel III (modified by the American Heart Association), the International Diabetes Federation (IDF), and the World Health Organization (WHO). The complication outcomes included coronary artery disease, renal failure, diabetes-related death, and the aggregate of these three major outcomes of diabetes (MOD). RESULTS—Metabolic syndrome prevalence ranged from 8% (IDF) to 21% (WHO). All definitions showed reasonable specificity (≥83%) for each outcome, while the WHO definition had the highest sensitivity for all outcomes except renal failure, for which eGDR was most sensitive. However, the components of each definition predicted better than the overall syndrome. Microalbuminuria was clearly the strongest predictor of all individual measures, yielding hazard ratios of 9 and 6 for mortality and MOD, respectively. CONCLUSIONS—Though the three metabolic syndrome classifications predict major complication outcomes in type 1 diabetes, their individual components predict better. Of the variables studied, including HbA1, microalbuminuria appears to be the best single predictor of MOD.

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Section: Results -Of the 514 Participantsmentioning

confidence: 84%

The Prediction of Major Outcomes of Type 1 Diabetes: a 12-Year Prospective Evaluation of Three Separate Definitions of the Metabolic Syndrome and Their Components and Estimated Glucose Disposal Rate

2007

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“…Most surprisingly, their predictive power surpasses that of classic risk markers of cardiovascular and atherosclerotic disease (5). Albuminuria is related to intrarenal hydraulic pressure, podocyte function, electric charge, and increased permeability, provoked by endothelial dysfunction (6). Prospective studies have demonstrated the predictive value of endothelial dysfunction for future cardiovascular morbid events when assessed in the peripheral and coronary circulation (7)(8)(9) and most likely, although not yet proven, in the renal circulation.…”

mentioning

confidence: 99%

Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes

Schmieder

Delles²,

Mimran³

et al. 2007

Diabetes Care

117

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OBJECTIVE -One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function.RESEARCH DESIGN AND METHODS -In a multicenter, prospective, double-blind, forced-titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate Ͼ80 ml/min, and normo-or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks. RESULTS -The mean, reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 Ϯ 9.0 ml/min before therapy to 105.2 Ϯ 9.7 ml/min at the end of treatment (P Ͻ 0.001). With ramipril, RPF response to L-NMMA increased from 60.1 Ϯ 12.2 to 87.8 Ϯ 9.2 ml/min (P ϭ 0.018). The adjusted difference between treatments was Ϫ17.1 Ϯ 13.7 ml/min (P ϭ 0.214). In accordance, telmisartan increased RPF at rest (i.e., without L-NMMA) from 652.0 Ϯ 27.0 to 696.1 Ϯ 31.0 ml/min (P ϭ 0.047), whereas ramipril produced no significant changes in RPF. The more the basal NO activity improved, the greater was the vasodilatory effect on renal vasculature (r ϭ 0.47, P Ͻ 0.001).CONCLUSIONS -In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function. Diabetes Care 30:1351-1356, 2007T he close link between cardiovascular and renal changes due to cardiovascular risk factors, such as arterial hypertension and diabetes, has stimulated increasing interest (1-3). Albuminuria and decreased renal function, which are both primarily known to predict renal outcome, have now been identified as excellent predictors of cardiovascular morbidity and mortality (2-4). Most surprisingly, their predictive power surpasses that of classic risk markers of cardiovascular and atherosclerotic disease (5). Albuminuria is related to intrarenal hydraulic pressure, podocyte function, electric charge, and increased permeability, provoked by endothelial dysfunction (6). Prospective studies have demonstrated the predictive value of endothelial dysfunction for future cardiovascular morbid events when assessed in the peripheral and coronary circulation (7-9) and most likely, although not yet proven, in the renal circulation.The endothelium is a major regulator of vascular homeostasis, with functional integrity being essential for the maintenance of blood flow and antithrombotic activity (10). Nitric oxide (NO), formed from L-arginine in the presence of NO synthase, is released by the vascular endothelial cells and brings about relaxation of vascular tissue and inhibition of platelet aggregation and adhesion (11). Endothelial dysfunction occurs as a result of impairment of NO synthesis or increased NO degradation and has been detected in patients with hypertension, peripheral arterial occlusive disease, and chronic re...

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“…Both macrovascular and microvascular injury, with endothelial dysfunction as the main initiating event, are thought to underlie diabetic disease complications (de Jager et al, 2006;Ladeia et al, 2005). Prospective studies have demonstrated that endothelial dysfunction is highly predictive of future cardiovascular disease (Schachinger et al, 2000).…”

Section: Diabetes Mellitus and The Renin-angiotensin Systemmentioning

confidence: 99%

Diabetic complications: A role for the prorenin–(pro)renin receptor–TGF-β1 axis?

Heuvel

Batenburg

Danser

2009

Molecular and Cellular Endocrinology

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might be a mediator of the endothelial dysfunction leading to both micro-and macrovascular complications of diabetes. The elevated plasma levels of prorenin in diabetic subjects with microvascular complications might be part of this discordant RAS, especially since the plasma renin levels in diabetes are low. Prorenin, previously thought of as an inactive precursor of renin, is now known to bind to a (pro)renin receptor, thus activating locally angiotensin-dependent and -independent pathways. In particular, the stimulation of the transforming growth factor-β (TGF-β) system by prorenin could be an important contributor to diabetic disease complications. This review discusses the concept of the prorenin -(pro)renin receptor -TGF-β 1 axis, concluding that interference with this pathway might be a next logical step in the search for new therapeutic regimens to reduce diabetes-related morbidity and mortality.

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Endothelial Dysfunction Is Correlated With Microalbuminuria in Children With Short-Duration Type 1 Diabetes

Cited by 38 publications

References 13 publications

The Prediction of Major Outcomes of Type 1 Diabetes: a 12-Year Prospective Evaluation of Three Separate Definitions of the Metabolic Syndrome and Their Components and Estimated Glucose Disposal Rate

The Prediction of Major Outcomes of Type 1 Diabetes: a 12-Year Prospective Evaluation of Three Separate Definitions of the Metabolic Syndrome and Their Components and Estimated Glucose Disposal Rate

Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes

Diabetic complications: A role for the prorenin–(pro)renin receptor–TGF-β1 axis?

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