Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity

Lockhart, Christopher; Agnew, Christina; McCann, Aaron; Hamilton, Paul; Quinn, Cathy E.; McCall, D.; Plumb, Rick; McClenaghan, Vivienne; McGivern, R. C.; Harbinson, Mark; McVeigh, Gary E.

doi:10.1042/cs20100448

Cited by 23 publications

(19 citation statements)

References 48 publications

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“…Our conclusions are in contrast to others who have pointed out that endothelial dysfunction is an important predictor of microangiopathic complications (1,32,33). This could be partially explained by the fact that these studies were performed in younger cohorts with a shorter duration of diabetes (12) and used the postocclusive reactive hyperemia method or venous congestion to achieve maximal recruitment of capillaries (5,10).…”

Section: Discussioncontrasting

confidence: 99%

Decreased Reactivity of Skin Microcirculation in Response to l-Arginine in Later-Onset Type 1 Diabetes

et al. 2013

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OBJECTIVEThe aim of our study was to evaluate the vasodilatory effect of l-arginine infusion on the skin microcirculation and to assess the relationship between this effect and the presence of microangiopathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSCapillaroscopy was performed before and after l-arginine infusion in 48 diabetic patients (26 women and 22 men; age, 39.8 ± 6.3 years) and 24 volunteers free of any chronic disease (13 women and 11 men; age, 38.0 ± 6.7 years). The skin microcirculation reactivity, as expressed by the percentage of area covered by capillaries (coverage) and the distance between capillaries (distance), and the relationship between microcirculation reactivity and the presence of microangiopathic complications were assessed.RESULTSThe distance before l-arginine infusion was significantly lower in patients than in controls (221 [153–311] vs. 240 [185–356] µm; P = 0.02) and did not differ after l-arginine infusion (223.5 [127–318] vs. 242.5 [181–341] µm; P = 0.27). The difference between the coverage values obtained before and after l-arginine infusion (Δcoverage) was significantly different from zero in the control group but not in the diabetes group. Patients with later onset of diabetes were characterized by decreased skin microcirculation reactivity when compared with patients with earlier onset of diabetes (−1.18 [−5.07 to 11.60] vs. 1.36 [−6.00 to 8.06]; P = 0.02) despite the higher prevalence of retinopathy in patients with earlier onset of diabetes (64% vs. 26%; P = 0.02).CONCLUSIONSSkin microvascular reactivity is impaired in patients with later onset of type 1 diabetes. Capillaroscopy with l-arginine infusion is useful for the identification of skin microangiopathy in type 1 diabetes.

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Section: Discussioncontrasting

confidence: 99%

Decreased Reactivity of Skin Microcirculation in Response to l-Arginine in Later-Onset Type 1 Diabetes

et al. 2013

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“…Endothelial function can be assessed noninvasively using the ultrasound-based technique of flow-mediated dilatation (FMD) [13], in which inflation of a blood pressure cuff downstream of the vessel under study produces a stimulus for endothelial production of vasoactive autocoids (such as nitric oxide) that leads to upstream arterial dilatation [14]. Impaired FMD has been associated with both cardiovascular risk factors [13, 15–17] and the presence of coronary artery disease at angiography [18]. Furthermore, impaired FMD has been shown to predict incident of CVD in certain populations [19, 20].…”

Section: Introductionmentioning

confidence: 99%

Endothelial Function in Women with and without a History of Glucose Intolerance in Pregnancy

Brewster

Floras

Zinman

et al. 2013

Journal of Diabetes Research

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Background/Aims. Gestational diabetes mellitus (GDM) and milder gestational impaired glucose tolerance (GIGT) identify women who are at risk of developing cardiovascular disease. Endothelial dysfunction, as indicated by impaired flow-mediated dilatation (FMD) on brachial artery ultrasound, is an early marker of vascular disease. Thus, we sought to evaluate endothelial function in women with and without recent glucose intolerance in pregnancy. Methods. One-hundred and seventeen women underwent oral glucose tolerance testing (OGTT) in pregnancy, enabling stratification into those with normal gestational glucose tolerance (n = 59) and those with GDM or GIGT (n = 58). 6 years postpartum, they underwent a repeat of OGTT and brachial artery FMD studies, enabling assessment of FMD and 4 secondary vascular measures: FMD after 60 seconds (FMD60), baseline arterial diameter, peak shear rate, and reactive hyperemia. Results. There were no differences between the normal gestational glucose tolerance and GDM/GIGT groups in FMD (mean 8.5 versus 9.3%, P = 0.61), FMD60 (4.1 versus 5.1%, P = 0.33), baseline diameter (3.4 versus 3.4 mm, P = 0.66), peak shear rate (262.6 versus 274.8 s−1, P = 0.32), and reactive hyperemia (576.6 versus 496.7%, P = 0.07). After covariate adjustment, there were still no differences between the groups. Conclusion. Despite their long-term cardiovascular risk, women with glucose intolerance in pregnancy do not display endothelial dysfunction 6 years postpartum.

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“…For example, animal models of type 1 DM have demonstrated a consistent state of NO-mediated renal hyperfiltration, despite evidence of decreased NO activity and endothelial dysfunction in large vessels (6,37). This paradoxical state of high renal versus low macrovascular NO bioactivity may also exist in humans, since type 2 DM patients exhibit a positive association between urinary NO excretion and creatinine clearance in observational cohort studies, despite evidence of macrovascular dysfunction and low NO bioactivity (25,26).…”

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confidence: 99%

Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus

Cherney

Reich

Jiang

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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(DM) suggest that increased nitric oxide (NO) bioactivity contributes to renal hyperfiltration. However, the role of NO in mediating hyperfiltration has not been fully elucidated in humans. Our aim was to examine the effect of NO synthase inhibition on renal and peripheral vascular function in normotensive subjects with uncomplicated type 1 DM. Renal function and brachial artery flow-mediated vasodilatation (FMD) were measured before and after an intravenous infusion of the NO synthase inhibitor N G -nitro-Larginine methyl ester (L-NMMA) in 21 healthy control and 37 type 1 DM patients. Measurements in DM participants were made under clamped euglycemic conditions. The effect of L-NMMA on circulating and urinary NO metabolites (NOx) and cGMP and on urinary prostanoids was also determined. Baseline characteristics were similar in the two groups. For analysis, the DM patients were divided into those with hyperfiltration (DM-H, n ϭ 18) and normal glomerular filtration rate (GFR) levels (DM-N, n ϭ 19). Baseline urine NOx and cGMP were highest in DM-H. L-NMMA led to a decline in GFR in DM-H (152 Ϯ 16 to 140 Ϯ 11 ml·min Ϫ1 ·1.73 m Ϫ2 ) but not DM-N or healthy control participants. The decline in effective renal plasma flow in response to L-NMMA (806 Ϯ 112 to 539 Ϯ 80 ml·min Ϫ1 ·1.73 m Ϫ2 ) in DM-H was also exaggerated compared with the other groups (repeated measures ANOVA, P Ͻ 0.05), along with declines in urinary NOx metabolites and cGMP. Baseline FMD was lowest in DM-H compared with the other groups and did not change in response to L-NMMA. L-NMMA reduced FMD and plasma markers of NO bioactivity in the healthy control and DM-N groups. In patients with uncomplicated type 1 DM, renal hyperfiltration is associated with increased NO bioactivity in the kidney and reduced NO bioactivity in the systemic circulation, suggesting a paradoxical state of high renal and low systemic vascular NO bioactivity. endothelial function; hyperfiltration; nitric oxide; type 1 diabetes GLOMERULAR HYPERFILTRATION is an early renal hemodynamic change in animal and human studies of diabetes mellitus (DM) and may help to predict the risk for the subsequent development of diabetic nephropathy (38). The pathogenesis of hyperfiltration is complex and involves both tubuloglomerular feedback and hemodynamic abnormalities. Renal hemodynamic changes associated with hyperfiltration include afferent vasodilatation and efferent constriction. Hyperfiltration is, however, only partially corrected after selective cyclooxygenase-2 inhibition (predominant afferent constriction) or renin angiotensin system (RAS) blockade (predominant efferent vasodilatation) in humans with uncomplicated type 1 DM (8, 54). These findings suggest the presence of nonprostaglandin, non-RAS-dependent hemodynamic mechanisms that perpetuate the hyperfiltration state (60).Functional expression studies in DM models have determined that endothelial nitric oxide (NO) synthase (eNOS) expression is consistently upregulated and localized to the afferent arteriole, renal cortex, and medull...

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Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity

Cited by 23 publications

References 48 publications

Decreased Reactivity of Skin Microcirculation in Response to l-Arginine in Later-Onset Type 1 Diabetes

Decreased Reactivity of Skin Microcirculation in Response to l-Arginine in Later-Onset Type 1 Diabetes

Endothelial Function in Women with and without a History of Glucose Intolerance in Pregnancy

Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus

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