Noninvasive Detection of Functional Alterations of the Arterial Wall in IDDM Patients With and Without Microalbuminuria

Zenere, B. M.; Arcaro, Guido; Saggiani, F.; Rossi, Luca; Muggeo, Michele; Lechi, Alessandro

doi:10.2337/diacare.18.7.975

Cited by 111 publications

(75 citation statements)

References 37 publications

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“…Not surprisingly, rat, STZ, 5-26w Heart serotonin; SNPÖ vitamin E 5-26w (T) SOD (P) Quilley et al, 1996 rat, STZ, 4-6w Heart BK; ARI 4-6w (T) COX blockade (N) Fulton et al, 1996 rat, STZ, 4-6w Kidney ACh;, BK; SNPÖ L-arginine (P) COX blockade (N) negative results were generally obtained in patients with normoalbuminuria and relatively good metabolic control (Smits et al, 1993;Lambert et al, 1996;Enderle et al, 1998). When microalbuminuric patients were included in the study population, impaired endothelium-dependent vasodilatation was consistently reported (Zenere et al, 1995;Clarkson et al, 1996;Lekakis et al, 1997;Arcaro et al, 1999). Studies investigating endothelial function in animal models of type II diabetes are scarce and have yielded con¯icting results.…”

Section: Experimental and Clinical Evidence For The Presence Of Impaimentioning

confidence: 96%

“…In one of the few experimental studies where a decreased response to nitrovasodilators was observed, it was preceded by a disturbed response to ACh (Dai et al, 1993). An impaired response to nitrovasodilators was more frequently found in humans (McVeigh et al, 1992;Calver et al, 1992;Zenere et al, 1995;Williams et al, 1996;Clarkson et al, 1996;Lekakis et al, 1997), perhaps due to the more advanced state of the diabetes. In support of this contention, the dilatation to isosorbide dinitrate was decreased in microalbuminuric, but not in normoalbuminuric patients (Lekakis et al, 1997).…”

Section: Mechanisms Of Impaired Endothelium-dependent Vasodilatation mentioning

confidence: 99%

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Endothelial dysfunction in diabetes

Vriese

Verbeuren

Voorde

et al. 2000

British J Pharmacology

1,015

769

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Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease. The endothelium controls the tone of the underlying vascular smooth muscle through the production of vasodilator mediators. The endothelium-derived relaxing factors (EDRF) comprise nitric oxide (NO), prostacyclin, and a still elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been demonstrated in various vascular beds of di erent animal models of diabetes and in humans with type 1 and 2 diabetes. Several mechanisms of endothelial dysfunction have been reported, including impaired signal transduction or substrate availibility, impaired release of EDRF, increased destruction of EDRF, enhanced release of endothelium-derived constricting factors and decreased sensitivity of the vascular smooth muscle to EDRF. The principal mediators of hyperglycaemia-induced endothelial dysfunction may be activation of protein kinase C, increased activity of the polyol pathway, non-enzymatic glycation and oxidative stress. Correction of these pathways, as well as administration of ACE inhibitors and folate, has been shown to improve endothelium-dependent vasodilation in diabetes. Since the mechanisms of endothelial dysfunction appear to di er according to the diabetic model and the vascular bed under study, it is important to select clinically relevant models for future research of endothelial dysfunction.

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Section: Experimental and Clinical Evidence For The Presence Of Impaimentioning

confidence: 96%

Section: Mechanisms Of Impaired Endothelium-dependent Vasodilatation mentioning

confidence: 99%

Endothelial dysfunction in diabetes

Vriese

Verbeuren

Voorde

et al. 2000

British J Pharmacology

1,015

769

View full text Add to dashboard Cite

show abstract

“…In particular, microalbuminuria has been viewed as a marker of vascular dysfunction in both the kidneys and systemic vasculature. 24 Studies in both diabetic 25,26 and nondiabetic 27,28 individuals indicate that elevated urinary albumin excretion is associated with abnormalities in tests of endothelial function. Whether such abnormalities may contribute to hypertension is unknown, although hypertension UACR quartiles are gender specific.…”

Section: Possible Mechanismsmentioning

confidence: 99%

Low-Grade Albuminuria and the Risks of Hypertension and Blood Pressure Progression

et al. 2005

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Background-It has been postulated that glomerular hyperfiltration and endothelial dysfunction are early features of essential hypertension that may antedate blood pressure elevation. Microalbuminuria, a marker of glomerular hyperfiltration and endothelial dysfunction, has been described in individuals with established hypertension, but its role as a biomarker of preclinical stages of this disease has not been investigated prospectively. Methods and Results-We examined the association between urinary albumin excretion and the risks of hypertension and blood pressure progression in 1499 nonhypertensive individuals (58% women) without diabetes. During a mean follow-up of 2.9 years, 230 participants (15%) developed hypertension and 499 (33%) progressed to a higher blood pressure category (defined by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). In multivariable logistic regressions that adjusted for known risk factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment in log UACR

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“…Endothelial dysfunction has consistently been reported in type 2 diabetes [33], in contrast to type 1 diabetes, where only half of the studies have reported it [33]. It has been suggested that dysfunction in endothelialdependent and -independent vasodilatation is a continuum, with people with good glycaemic control and normal albumin excretion at one end, and those with microalbuminuria, poor glycaemic control and long duration of diabetes at the other [33][34][35]. It is not known whether differences in the number of circulating EPCs could explain the gradient in endothelial dysfunction in people with type 1 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

et al. 2009

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Aims/hypothesis Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima-media thickness (CIMT). Methods We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. Results CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46-69%; p=0.004-0.043). In people with type 1 diabetes, FMD was reduced by 45% (p<0.001) and CIMT increased by 25% (p<0.001), these being correlated (r=−0.25, p=0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r =0.25, p = 0.037) and CD34+ (r=0.34, p=0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r=−0.27, p=0.028 and r=−0.24, p=0.048, respectively). Conclusions/interpretation These findings suggest that abnormalities of endothelial function in addition to proinflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events.

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Noninvasive Detection of Functional Alterations of the Arterial Wall in IDDM Patients With and Without Microalbuminuria

Abstract: These results confirm a reduced vasodilatory capacity in diabetes mellitus, with a more marked alteration in microalbuminuric diabetic subjects. This reliable, noninvasive evaluation of arterial function is particularly useful for early diagnosis of vascular involvement.

Cited by 111 publications

References 37 publications

Endothelial dysfunction in diabetes

Endothelial dysfunction in diabetes

Low-Grade Albuminuria and the Risks of Hypertension and Blood Pressure Progression

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

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