Coronary Microvascular Adaptation to Myocardial Metabolic Demand Can Be Restored by Inhibition of Iron-Catalyzed Formation of Oxygen Free Radicals in Type 2 Diabetic Patients

Nitenberg, A; Ledoux, Séverine; Valensi, P.; Sachs, R. N.; Antony, Isabelle

doi:10.2337/diabetes.51.3.813

Cited by 40 publications

(18 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, some animal experimental data regarding the effect of manipulating iron stores on atherosclerosis and human data showing improvement of vascular structure and function following iron depletion (16,17,72,75) are both consistent with the theory that iron contributes to the development of vascular disease. However, the current epidemiological data associating iron stores with either atherosclerosis or coronary heart disease (reviewed in 78) do not fully support this hypothesis.…”

Section: A Iron Depletion and Diabetic Metabolic Controlsupporting

confidence: 52%

“…In type 2 diabetic patients, coronary artery responses to cold stress testing improved substantially after deferoxamine administration (16). Similarly, iron chelation was shown to ameliorate the endothelial dysfunction of patients with coronary heart disease (17).…”

Section: A Iron Depletion and Diabetic Metabolic Controlmentioning

confidence: 94%

“…A significant impact of tissue iron excess on systemic effects of diabetes is suggested by recent reports in which iron appears to influence the development of diabetic nephropathy and vascular dysfunction. In this sense, intravenous administration of deferoxamine resulted in improved coronary artery responses to cold stress testing in type 2 diabetic subjects (16) and in amelioration of endothelial dysfunction in subjects with coronary heart disease (17).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cross-Talk Between Iron Metabolism and Diabetes

Fernández‐Real¹,

López‐Bermejo²,

Ricart³

2002

Diabetes

593

411

View full text Add to dashboard Cite

Emerging scientific evidence has disclosed unsuspected influences between iron metabolism and type 2 diabetes. The relationship is bi-directional-iron affects glucose metabolism, and glucose metabolism impinges on several iron metabolic pathways. Oxidative stress and inflammatory cytokines influence these relationships, amplifying and potentiating the initiated events. The clinical impact of these interactions depends on both the genetic predisposition and the time frame in which this network of closely related signals acts. In recent years, increased iron stores have been found to predict the development of type 2 diabetes while iron depletion was protective. Iron-induced damage might also modulate the development of chronic diabetes complications. Iron depletion has been demonstrated to be beneficial in coronary artery responses, endothelial dysfunction, insulin secretion, insulin action, and metabolic control in type 2 diabetes. Here, we show that iron modulates insulin action in healthy individuals and in patients with type 2 diabetes. The extent of this influence should be tested in large-scale clinical trials, searching for the usefulness and cost-effectiveness of therapeutic measures that decrease iron toxicity. The study of individual susceptibility and of the mechanisms that influence tissue iron deposition and damage are proposed to be valuable in anticipating and treating diabetes complications. Diabetes 51:2348 -2354, 2002

show abstract

Section: A Iron Depletion and Diabetic Metabolic Controlsupporting

confidence: 52%

Section: A Iron Depletion and Diabetic Metabolic Controlmentioning

confidence: 94%

mentioning

confidence: 99%

See 1 more Smart Citation

Cross-Talk Between Iron Metabolism and Diabetes

Fernández‐Real¹,

López‐Bermejo²,

Ricart³

2002

Diabetes

593

411

View full text Add to dashboard Cite

show abstract

“…It has been suggested that oxidative stress, which is increased in diabetes (27), can depress endothelium-mediated dilation by inactivation of nitric oxide (28). Indeed, an antioxidant agent could restore endothelium-dependent dilation in diabetes (5,29,30). On the other hand, it has been shown that there was a failure of coronary blood flow to adequately increase in diabetic patients because of impaired metabolic microvascular dilation (26,31), which could mask the ability of epicardial arteries to dilate in the absence of flow velocity increase.…”

Section: Cpt Response As a Witness Of Coronary Endothelial Dysfunctionmentioning

confidence: 99%

Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors

et al. 2004

Self Cite

View full text Add to dashboard Cite

OBJECTIVE -Endothelium-dependent coronary dilation is impaired in diabetic patients and has been found to independently predict cardiovascular events (CVEs) in patients with multiple coronary risk factors. The aim of this study was to evaluate the outcome of type 2 diabetic patients on the basis of epicardial coronary dysfunction.RESEARCH DESIGN AND METHODS -We examined 56 control subjects (aged 51.7 Ϯ 6.4 years) using coronary artery response to the cold pressor test (quantitative coronary angiography) and compared them with 72 type 2 diabetic patients (aged 50.3 Ϯ 8.5 years) without other major coronary risk factors.RESULTS -Average diameter change was 17.2 Ϯ 10.4% in the control subjects, dilation occurred in 91.1% of subjects, no change occurred in 8.9%, and there was no constriction. Average diameter change was Ϫ14.4 Ϯ 12.1% in diabetic patients (P Ͻ 0.001 vs. control subjects), constriction occurred in 73.6%, no change occurred in 26.4%, and there was no dilation. CVEs were recorded with a mean follow-up of 45 Ϯ 19 months. There was 1 CVE in the control group and 26 CVEs in 18 of 72 diabetic patients (P Ͻ 0.001 vs. control subjects), with 23 events in 16 of 53 diabetic patients with coronary artery constriction (P Ͻ 0.001 vs. control subjects), and 3 events in 2 of 19 diabetic patients with no diameter change (NS vs. control subjects).CONCLUSIONS -In type 2 diabetic patients without other major coronary risk factors, constriction of angiographically normal coronary arteries to the cold pressor test is predictive of long-term CVEs. Diabetes Care 27:208 -215, 2004I n diabetic patients, coronary atherosclerosis develops earlier than in other subjects and accounts for excessive morbidity and mortality (1). Because it is well established that the endothelium plays a key role in the regulation of vascular tone and the development of atherosclerosis (2), it has been suggested that endothelial dysfunction could be a predictor of cardiovascular risk (3). It has been shown that endothelium-dependent epicardial coronary artery vasodilation in response to acetylcholine (4) or physiological stimuli (5) is impaired in diabetic patients, suggesting that endothelial dysfunction occurs before the development of overt atherosclerosis. Recently, coronary endothelial dysfunction, evidenced by intracoronary acetylcholine, has been demonstrated to be an independent predictor of cardiovascular events (CVEs) in patients with coronary artery disease (6 -8) and patients with coronary risk factors (8). The cold pressor test (CPT), which activates the sympathetic nervous system, induces dilation of coronary arteries in control subjects and constriction of atherosclerotic coronary arteries (6,9,10). In diabetic patients, CPT has been shown to induce coronary artery constriction (5), which may reflect endothelial dysfunction.The purpose of the present study was to evaluate the ability of the epicardial coronary response to the CPT to predict CVEs in type 2 diabetic patients with angiographically normal coronary arteries and no other ma...

show abstract

“…The incidence of diabetes, postprandial serum insulin and pancreatic insulin sensitivity, i.e., beta cell function were al improved in subjects with previous phlebotomy treatment [143] . Iron removal also improved coronary vascular dysfunction in patients with T2DM [144] and endothelial function in patients with known coronary artery disease and in subjects with primary iron overload [145,146] . Blood donations were linked to insulin sensitivity even in healthy subjects [46] .…”

Section: What Is the Therapeutic Potential Of Modulating Iron Stores mentioning

confidence: 99%

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Aigner

Weiss

Datz

2014

WJH

View full text Add to dashboard Cite

Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the "dysmetabolic iron overload syndrome". Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxylradicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications.

show abstract

Coronary Microvascular Adaptation to Myocardial Metabolic Demand Can Be Restored by Inhibition of Iron-Catalyzed Formation of Oxygen Free Radicals in Type 2 Diabetic Patients

Cited by 40 publications

References 51 publications

Cross-Talk Between Iron Metabolism and Diabetes

Cross-Talk Between Iron Metabolism and Diabetes

Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Contact Info

Product

Resources

About