Insulin Sensitivity, Vascular Reactivity, and Clamp-Induced Vasodilatation in Essential Hypertension

Natali, Andrea; Taddei, Stefano; Galvan, Alfredo Quiñones; Camastra, Stefania; Baldi, Simona; Frascerra, Silvia; Virdis, Agostino; Sudano, Isabella; Salvetti, Antonio; Ferrannini, Ele

doi:10.1161/01.cir.96.3.849

Cited by 63 publications

(48 citation statements)

References 32 publications

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“…To our knowledge, the present study is the first to report a direct association between insulin resistance and vascular endothelial dysfunction in type 2 diabetes, whereas such an association has not been observed in patients with obesity (14) or essential hypertension (15) or in normal subjects (13). This suggests a unique sensitivity of the endothelium of diabetic patients to the detrimental effect of insulin resistance; therefore, it is not surprising that treatment with tiazolidinediones has been shown to induce a concomitant amelioration of vascular endothelial function in type 2 diabetic (43) but not obese (14) patients.…”

Section: Discussioncontrasting

confidence: 51%

“…In type 2 diabetes, however, no study has evaluated whether insulin resistance, when measured directly, clusters with these abnormalities. In normal (13) and obese (14) subjects and in patients with essential hypertension (15), the vascular response to endothelium-dependent vasodilators has been reported to be unrelated to insulin resistance. Previous studies in type 2 diabetes (Table 1) have generally found an impairment in endothelium-dependent vasodilatation; endothelium-independent dilatation, however, has been variably reported to be reduced or unaffected.…”

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confidence: 99%

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Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes

Natali

Toschi²,

Baldeweg³

et al. 2006

Diabetes

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174

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1Vascular dysfunction, low-grade inflammation, insulin resistance, and impaired fibrinolysis have each been reported to be present in type 2 diabetes, but their relationships, and the role of obesity, have not been investigated. We measured insulin sensitivity (euglycemic clamp), forearm blood flow responses to graded local acetylcholine (Ach) and sodium nitroprusside (SNP) infusions, plasma concentrations of tumor necrosis factor (TNF)-␣, interleukin (IL)-6, von Willebrand factor (vWF), plasminogen activator inhibitor (PAI)-1, tissue plasminogen activator (tPA), and high-sensitivity C-reactive protein (hs-CRP) in 81 diabetic patients. When patients were stratified by insulin resistance, more severe insulin resistance was associated (P < 0.05) with overweight, central fat distribution, hypertension, and dyslipidemia (with similar sex distribution, age, fasting plasma glucose, and HbA 1c ). With regard to vascular function, both endothelium-dependent (Ach) (؊22, ؊40, and ؊52%; P < 0.0001) and -independent (SNP) (؊3, ؊7, and ؊27%; P < 0.02) vasodilatation were progressively reduced across insulin resistance tertiles. In multivariate analysis, inflammatory markers (IL-6, hs-CRP, and TNF-␣) were independently associated with insulin resistance and fasting glycemia, fibrinolytic markers PAI-1 and tPA with insulin resistance and central fat distribution, and vascular indexes (vWF, Ach, and SNP vasodilation) with insulin resistance and obesity or cytokines (TNF-␣ or IL-6). In type 2 diabetes, insulin resistance is associated with vascular dysfunction/damage, impaired fibrinolysis, and low-grade inflammation independently of obesity and poor glycemic control.

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Section: Discussioncontrasting

confidence: 51%

mentioning

confidence: 99%

Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes

Natali

Toschi²,

Baldeweg³

et al. 2006

Diabetes

Self Cite

174

131

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“…Using the forearm technique, we have previously shown that EDV is reduced in diabetic patients in proportion to their degree of insulin resistance [46]. Insulin resistance, however, does not cluster with EDV in nondiabetic normotensive participants [47] or in patients with essential hypertension [48]. Therefore, we must postulate that long-standing hyperglycaemia on its own or in interaction with insulin resistance, directly or via accumulation of AGE compromises endothelium-dependent vascular functions.…”

Section: Discussionmentioning

confidence: 99%

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

et al. 2008

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Aims/hypothesis Hyperglycaemia and hyperinsulinaemia have opposite effects on endothelium-dependent vasodilatation in microcirculation, but the net effect elicited by glucose ingestion and the separate influence of glucose tolerance are unknown. Methods In participants with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or diabetic glucose tolerance, multiple plasma markers of both oxidative stress and endothelial activation, and forearm vascular responses (plethysmography) to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) infusions were measured before and after glucose ingestion. In another IGT group, we evaluated the time-course of the skin vascular responses (laser Doppler) to ACh and SNP (by iontophoresis) 1, 2 and 3 h into the OGTT; the plasma glucose profile was then reproduced by means of a variable intravenous glucose infusion and the vascular measurements repeated. Results Following oral glucose, plasma antioxidants were reduced by 5% to 10% (p<0.01) in all patient groups. The response to acetylcholine was not affected by glucose ingestion in any group, while the response to SNP was attenuated, particularly in the IGT group. The ACh:SNP ratio was slightly improved therefore in all groups, even in diabetic participants, in whom it was impaired basally. A time-dependent improvement in ACh:SNP ratio was also observed in skin microcirculation following oral glucose; this improvement was blunted when matched hyperglycaemia was coupled with lower hyperinsulinaemia (intravenous glucose). Conclusions/interpretation Regardless of glucose tolerance, oral glucose does not impair endothelium-dependent vasodilatation either in resistance arteries or in the microcirculation, despite causing increased oxidative stress; the endogenous insulin response is probably responsible for countering any inhibitory effect on vascular function.

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“…Indeed, this is consistent with insulin's vasodilating properties in normal individuals and with graded amounts of insulin-induced vasodilation in hypertensives grouped by levels of insulin sensitivity. 24 However, levels of or changes in Ca cyt cannot be solely responsible for the state of smooth muscle contraction. As an example of this, the hypertensives with low Ca cyt clearly have a process ongoing that sustains their higher level of blood pressure, which may not be calcium mediated.…”

Section: Discussionmentioning

confidence: 99%

Increased red cell sodium-lithium countertransport and lymphocyte cytosolic calcium are separate phenotypes in patients with essential hypertension

et al. 2002

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Increased red blood cell sodium-lithium countertransport (SLC) activity and elevated intracellular calcium have been observed in hypertensive patients. The association of these ion transport abnormalities with each other and with another phenotype, insulin resistance, has been suggested. We investigated whether elevated SLC activity and increased lymphocyte cytosolic calcium (Ca cyt ) occur in the same individuals and whether either is associated with hyperinsulinaemia. We measured SLC activity, lymphocyte Ca cyt and fasting insulin levels in hypertensive patients and normal subjects. Consistent with prior studies, SLC activity was significantly and positively correlated with fasting insulin levels (r = 0.45, P Ͻ 0.01). However, SLC activity and lymphocyte Ca cyt were significantly but inversely correlated (r = −0.42, P Ͻ 0.01) and lymphocyte Ca cyt was also inversely correlated with fasting insulin (r = −0.55, P Ͻ

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Insulin Sensitivity, Vascular Reactivity, and Clamp-Induced Vasodilatation in Essential Hypertension

Cited by 63 publications

References 32 publications

Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes

Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

Increased red cell sodium-lithium countertransport and lymphocyte cytosolic calcium are separate phenotypes in patients with essential hypertension

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