Elevated Concentrations of Soluble E-Selectin and Vascular Cell Adhesion Molecule-1 in NIDDM: Effect of intensive insulin treatment

Albertini, Jean-Paul; Valensi, P.; Lormeau, B.; Aurousseau, M.H.; Ferrière, Françoise; Attali, Jean-Raymond; Gattegno, Liliane

doi:10.2337/diacare.21.6.1008

Cited by 115 publications

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“…In acute experiments, L-arginine is able to reverse the decreased NO availability induced by acute hyperglycemia in normal subjects. 19 Improved glycemic control obtained with either a 14-day continuous subcutaneous insulin infusion 12 or intensification of dietary or pharmacological treatment 11 reduced the level of the adhesion molecules whose concentration was increased when the glycemic control was poorer. In both studies, however, the posttreatment glycemic level was still elevated (7.5 to 7.8 mmol/L), and the diabetic patients evaluated in those studies had a long-lasting disease (Ϸ10 years).…”

Section: Marfella Et Al Circulating Adhesion Molecules In Humansmentioning

confidence: 99%

“…4 Type 2 diabetes mellitus is associated with an increased risk of premature atherosclerosis, 5,6 and the circulating levels of some CAMs are higher in the diabetic patient. [7][8][9][10][11][12][13] The relation between plasma glucose or insulin and circulating CAMs is poorly understood.…”

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confidence: 99%

“…The study protocol was designed to measure serum-soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) concentrations during acute hyperglycemia, with or without the accompanying hyperinsulinemia, in normal subjects and in newly diagnosed, complication-free type 2 diabetic patients. Because changes in soluble CAMs (sCAMs) are influenced by glycemic control, [11][12][13] we also assessed the behavior of sCAMs after the normalization of blood glucose levels in diabetic patients. Finally, we tested the effect of raised NO availability on increased sICAM-1 levels in diabetic patients.…”

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confidence: 99%

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Circulating Adhesion Molecules in Humans

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Background-We assessed the role of glucose and insulin in the regulation of circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) in normal subjects and in patients with type 2 diabetes. Methods and Results-Plasma glucose concentrations were acutely raised in 10 normal subjects and 10 newly diagnosed, complication-free type 2 diabetic patients and maintained at 15 mmol/L for 2 hours. In normal subjects, plasma sICAM-1, but not sVCAM-1, levels rose significantly (PϽ0.01) at 1 hour and returned to basal values at 2 hours. In another study, octreotide was infused during the hyperglycemic clamp to block the release of endogenous insulin; this prevented the late fall of plasma sICAM-l levels observed in under control clamp conditions. The diabetic patients had plasma sICAM-1 levels significantly higher (PϽ0.01) than those of the control subjects; plasma sVCAM-1 levels were similar. Both sICAM-l and sVCAM-1 concentrations did not change significantly during the control hyperglycemic clamp; however, octreotide infusion increased plasma sICAM-1 levels, which remained significantly (PϽ0.05) above baseline during the whole clamp. In an additional 10 type 2 diabetic patients, overnight euglycemia (plasma glucose 5.5 mmol/L) obtained with the aid of an artificial pancreas or supplementation with L-arginine (10 g PO for 30 days), the natural precursor of NO, normalized the increased plasma sICAM-1 levels. Conclusions-Acute hyperglycemia increases circulating sICAM-1 levels in normal subjects, whereas the correction of hyperglycemia with insulin or L-arginine supplementation restored to normal levels the increased plasma sICAM-1 levels of type 2 diabetic patients.

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Section: Marfella Et Al Circulating Adhesion Molecules In Humansmentioning

confidence: 99%

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confidence: 99%

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“…Most (20,(25)(26)(27)(28)(29), but not all (30,31), studies have shown sVCAM-1 levels to be increased among type 2 diabetic subjects as compared with nondiabetic subjects, and sVCAM-1 levels have been shown to be independently associated with carotid artery intima-media thickness in type 2 diabetes patients (29). In view of these considerations, we investigated the association of sVCAM-1 concentration and risk of cardiovascular and all-cause mortality among nondiabetic and type 2 diabetic subjects in a prospective, populationbased cohort study.…”

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confidence: 99%

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

et al. 2000

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Membrane-bound vascular cell adhesion molecule 1 (VCAM-1) allows the tethering and rolling of monocytes and lymphocytes as well as firm attachment and transendothelial migration of leukocytes. Soluble forms of VCAM (sVCAM-1) may serve as monitors of increased expression of membrane-bound VCAM-1 and thus may reflect progressive formation of atherosclerotic lesions. Levels of sVCAM-1 have been found to be increased among type 2 diabetic as compared with nondiabetic subjects. To study the association of plasma sVCAM-1 concentration and risk of cardiovascular and all-cause mortality among nondiabetic and diabetic subjects, we investigated an age-, sex-, and glucose-tolerance-stratified sample (n = 631) of a populationbased cohort aged 50-75 years that was followed p r o s p e c t i v e l y. Plasma levels of sVCAM-1 were determined in frozen -70°C baseline samples. After 7.4 years (mean) of follow-up, 107 (17%) subjects had died ( 4 2 of cardiovascular causes). In the entire group, increased sVCAM-1 levels were significantly associated with increased risk of cardiovascular mortality (relative risks [RRs] per 100 ng/ml sVCAM-1 increase, 1.10 [1.05-1.15] after adjustment for age, sex, and glucose tolerance status). This RR was somewhat diminished by further adjustment for the presence of hypertension and cardiovascular disease; levels of total, HDL, and LDL cholesterol and homocysteine; the presence of microalbuminuria (a putative marker of endothelial dysfunction); levels of von Willebrand factor (a marker of endothelial dysfunction) and C-reactive protein (a marker of low-grade inflammation); and estimates of glomerular filtration rate. However, the RR remained statistically significant. The RR among type 2 diabetic subjects was 1.13 (1.07-1.20) per 100 ng/ml sVCAM-1 increase after adjustment for age and sex, which was somewhat higher but not significantly different from the RR in nondiabetic subjects (P value for interaction term, 0.12). Further adjustment for other risk factors gave similar results. In conclusion, levels of sVCAM-1 are independently associated with the risk of cardiovascular mortality in type 2 diabetic subjects and therefore might be useful for identifying subjects at increased cardiovascular risk. Increased plasma sVCAM-1 levels may reflect progressive formation of atherosclerotic lesions, or sVCAM-1 itself may have bioactive properties related to cardiovascular risk. Our data, however, argue against the hypotheses of sVCAM-1 levels simply being a marker of endothelial dysfunction, of low-grade inflammation, or of an impaired renal function. D i a b e t e s 4 9 :4 8 5-491, 2000

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“…Improved metabolic control with insulin, however, was associated with reduced CRP concentration. In a previous study by another group, improved glycaemia with intensive insulin treatment in patients with Type II diabetes was associated with normalisation of initially increased E-selectin [4].…”

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confidence: 99%

Comments to: Yudkin J, Panahloo A, Stenhouwer C et al. (2000) The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects. Diabetologia 43: 1099-1106

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Diabetologia

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serve the effects of both lowered glucose and insulin concentrations on those same markers.On the other hand, endothelial function is highly variable between subjects and in the same subject over time. As reported by the authors in their references, acute hyperglycaemia attenuates endothelium-dependent vasodilation [5]. It is not known whether the usual oscillations of glucose concentration, as observed with premixed human soluble and isophane 30:70 once or twice daily, provoke changes in endothelial function or endothelial markers that might have masked the authors' findings. The use of continuous insulin infusion with stable glucose concentrations would have contributed to overcoming these difficulties.The authors have uncovered interesting aspects about the pathophysiology of inflammatory markers in Type II diabetes. Some field conditions with an acknowledged impact on vascular function (smoking [6] or recent infections [7]) are difficult to control. Finally, it cannot be excluded that genetic susceptibility to inflammation and insulin resistance contributes to a vicious cycle of events that cannot be prevented once Type II diabetes has become manifest [8].J.-M. Fernandez-Real and W. Ricart

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Elevated Concentrations of Soluble E-Selectin and Vascular Cell Adhesion Molecule-1 in NIDDM: Effect of intensive insulin treatment

Abstract: In poorly controlled NIDDM patients, sE-selectin levels are increased and significantly fall to normal after short-term improvement of glycemic control. This suggests that assaying sE-selectin makes it possible to detect endothelium activation and to follow its reversal with euglycemia.

Cited by 115 publications

References 20 publications

Circulating Adhesion Molecules in Humans

Circulating Adhesion Molecules in Humans

Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes: the Hoorn study.

Comments to: Yudkin J, Panahloo A, Stenhouwer C et al. (2000) The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects. Diabetologia 43: 1099-1106

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