Iron Overload and Glucose Metabolism in Subjects with β-thalassaemia Major : An Overview

2013 ◽  
Vol 9 (4) ◽  
pp. 332-341 ◽  
Author(s):  
Vincenzo Sanctis ◽  
Ashraf Soliman ◽  
Mohamed Yassin
2021 ◽  
Vol 10 (23) ◽  
pp. 5561
Author(s):  
Antonella Meloni ◽  
Laura Pistoia ◽  
Maria Rita Gamberini ◽  
Paolo Ricchi ◽  
Valerio Cecinati ◽  
...  

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension–Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.


2014 ◽  
Vol 4 (3) ◽  
pp. 25-26
Author(s):  
Farrukh Shah

Today a patient born with thalassaemia major can expect to have a near normal life expectancy and remain free of complications of iron overload with good monitoring and excellent transfusion and chelation regimes. Unfortunately patients still develop complications as a consequence of iron overload including endocrinopathies and cardiac failure. The main reason behind this failure of effective treatment is inadequate treatment. This can be due to either clinician related factors, patient related factors or lack of adequate provision of medicines and services. In this short paper I will highlight where the challenges lie with regards adherence to treatment and suggest approaches to manage this.


2011 ◽  
Vol 23 (01) ◽  
pp. 29-35
Author(s):  
Chin-Hsiung Hsieh ◽  
Yuan-An Ku ◽  
Lien-Hua Chiu ◽  
Tai-Horng Young ◽  
Yi-You Huang

Patients with beta-thalassaemia major need blood transfusion frequently during their whole life. However, frequent transfusions will eventually lead to the accumulation of trivalent iron, resulting in iron overload. To reduce iron overload, patients are administered regularly with intravenous or subcutaneous infusion of deferioxamine mesylate (DFO). Nevertheless, high costs of medication, poor patient compliance, and side effects limit its use and patient's acceptance. To overcome such drawbacks, we developed a novel transdermal delivery system to administer the DFO instead of traditional injections. We assayed the feasibility of fabricating a transdermal DFO patch using the single-layer drug-in-adhesive drug delivery system. We used the pressure-sensitive adhesives and hydrogels as the drug reservoirs and studied the release profile of DFO from the transdermal patches in vitro. In order to enhance the transdermal delivery rate, chemical enhancers, polysorbate 80 and oleic acid, and physical enhancer, ultrasound, were incorporated into the monolith DFO patches. Experimental results showed that the combination of polysorbate 80 and oleic acid in the pressure-sensitive adhesives enhanced the penetration efficiency through nude mice skin. The pretreatment of nude mice skin with ultrasound temporally changed the diffusional resistance and facilitated DFO penetration through the skin. We expect that the new delivery system can enable the drug to penetrate through skin at a stable rate and reach the circulation system successfully, thus allowing the concentration of drug to achieve the therapeutic effect.


2010 ◽  
Vol 84 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Meropi Dimitriadou ◽  
Athanasios Christoforidis ◽  
Marina Economou ◽  
Ioanna Tsatra ◽  
Efthimia Vlachaki ◽  
...  

2006 ◽  
Vol 134 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Kalistheni Farmaki ◽  
Nicholas Angelopoulos ◽  
George Anagnostopoulos ◽  
Efstathios Gotsis ◽  
Grigorios Rombopoulos ◽  
...  

2020 ◽  
Vol 191 (3) ◽  
Author(s):  
Zhenbin Wei ◽  
Gaohui Yang ◽  
Yumei Huang ◽  
Peng Peng ◽  
Liling Long ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3838-3838 ◽  
Author(s):  
Mark A. Tanner ◽  
John B. Porter ◽  
Mark A. Westwood ◽  
Sunil V. Nair ◽  
Lisa J. Anderson ◽  
...  

Abstract Introduction: Myocardial iron overload is a well established cause of heart failure in a number of haematological disorders and is the leading cause of death in β-thalassaemia major (TM). Once overt heart failure develops prognosis is very poor and it would therefore be desirable to identify patients at risk, prior to the development of symptomatic heart failure. Myocardial iron can now be rapidly and reproducibly assessed using a validated cardiac magnetic resonance (CMR) T2* technique. Left ventricular ejection fraction has been demonstrated to relate to myocardial T2* (normal >20ms), and accordingly iron overloaded patients with symptomatic heart failure are likely to have a low T2* but there are no reports of the myocardial T2* level in newly presenting patients with heart failure and the threshold for increased risk is also unknown. Purpose: To establish the distribution of myocardial T2* values in patients presenting with symptomatic heart failure secondary to iron overload. Methods: Database records of CMR T2* assessments over a 5 year period were reviewed to identify iron overloaded patients presenting with heart failure. Results: 28 patients (median age 29y, 11–79) with iron overload and documented heart failure were identified. 22 patients had thalassaemia major, 3 hereditary haemochromatosis, and 3 had miscellaneous transfusion dependent anaemias. The mean myocardial T2* in all groups was 6.8+/− 2.2ms reflecting severe iron loading by clinical criteria. See figure 1. Myocardial T2* values were similar between sub-groups as follows: TM patients 6.7+/− 2.4ms, haemochromatosis 7.7ms (6.7–7.4ms), miscellaneous 6.8ms (4.8–9.1ms). Conclusion: In this database review, the patients developing heart failure secondary to iron overload all had abnormal myocardial T2*, and overall 89% of heart failure patients had values less than 10ms, which reflects severe myocardial iron loading. This data suggests a myocardial T2* <10ms should be considered a threshold for risk of heart failure (with its attendant high mortality) and such patients should be treated aggressively with increased iron chelation. It also suggests that clinical heart failure occurs nearly exclusively in patients with severe myocardial iron loading. Distribution of myocardial T2+ values in symptomatic heart failure (n=28) Distribution of myocardial T2+ values in symptomatic heart failure (n=28)


2013 ◽  
Vol 304 (12) ◽  
pp. G1095-G1102 ◽  
Author(s):  
Xuming Jia ◽  
Jonghan Kim ◽  
Tania Veuthey ◽  
Chih-Hao Lee ◽  
Marianne Wessling-Resnick

The iron-diabetes hypothesis proposes an association between iron overload and glucose metabolism that is supported by a number of epidemiological studies. The prevalence of type 2 diabetes in patients with hereditary hemochromatosis and iron-loading thalassemia supports this hypothesis. The Belgrade rat carries a mutation in the iron transporter divalent metal transporter 1 (DMT1) resulting in iron-loading anemia. In this study, we characterized the glycometabolic status of the Belgrade rat. Belgrade rats displayed normal glycemic control. Insulin signaling and secretion were not impaired, and pancreatic tissue did not incur damage despite high levels of nonheme iron. These findings suggest that loss of DMT1 protects against oxidative damage to the pancreas and helps to maintain insulin sensitivity despite iron overload. Belgrade rats had lower body weight but increased food consumption compared with heterozygous littermates. The unexpected energy balance was associated with increased urinary glucose output. Increased urinary excretion of electrolytes, including iron, was also observed. Histopathological evidence suggests that altered renal function is secondary to changes in kidney morphology, including glomerulosclerosis. Thus, loss of DMT1 appears to protect the pancreas from injury but damages the integrity of kidney structure and function.


2017 ◽  
Vol 37 (5) ◽  
pp. 453-464 ◽  
Author(s):  
Alessia Pepe ◽  
Giuseppe Rossi ◽  
Anthony Bentley ◽  
Maria Caterina Putti ◽  
Ludovica Frizziero ◽  
...  

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