Diabetes and Glucose Metabolism in Thalassemia Major: An Update

Sanctis, Vincenzo De; Soliman, Ashraf T.; Elsedfy, Heba; Pepe, Alessia; Kattamis, Christos; Kholy, Mohamed El; Yassin, Mohamed A

doi:10.1586/17474086.2016.1136209

Cited by 44 publications

(68 citation statements)

References 39 publications

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“…We found that subjects with thalassemia who had low Mt/N had insulin resistance by both of these indices. Since Mt/N increased with age in our study, as does the prevalence of impaired glucose tolerance (42), this inverse correlation was unexpected. However, adults with metabolic syndrome with insulin resistance were reported to have lower mitochondrial content in leukocytes (17).…”

Section: Discussionsupporting

confidence: 43%

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Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Lal¹,

Gómez²,

Calloway³

2016

JCI Insight

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BACKGROUND Iron overload is the primary cause of morbidity in transfusion-dependent thalassemia. Increase in iron causes mitochondrial dysfunction under experimental conditions, but the occurrence and significance of mitochondrial damage is not understood in patients with thalassemia. METHODS Mitochondrial DNA (mtDNA) to nuclear DNA copy number (Mt/N) and frequency of the common 4977-bp mitochondrial deletion (ΔmtDNA4977) were quantified using a quantitative PCR assay on whole blood samples from 38 subjects with thalassemia who were receiving regular transfusions. RESULTS Compared with healthy controls, Mt/N and ΔmtDNA4977 frequency were elevated in thalassemia (P = 0.038 and P < 0.001, respectively). ΔmtDNA4977 was increased in the presence of either liver iron concentration > 15 mg/g dry-weight or splenectomy, with the highest levels observed in subjects who had both risk factors (P = 0.003). Myocardial iron (MRI T2* < 20 ms) was present in 0%, 22%, and 46% of subjects with ΔmtDNA4977 frequency < 20, 20–40, and > 40/1 × 107 mtDNA, respectively (P = 0.025). Subjects with Mt/N values below the group median had significantly lower Matsuda insulin sensitivity index (5.76 ± 0.53) compared with the high Mt/N group (9.11 ± 0.95, P = 0.008). CONCLUSION Individuals with transfusion-dependent thalassemia demonstrate age-related increase in mtDNA damage in leukocytes. These changes are markedly amplified by splenectomy and are associated with extrahepatic iron deposition. Elevated mtDNA damage in blood cells may predict the risk of iron-associated organ damage in thalassemia.

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Section: Discussionsupporting

confidence: 43%

“…Iron overload in thalassemia is associated with early occurrence of insulin resistance with subsequent pancreatic damage and insulin deficiency leading to diabetes mellitus (42). HOMA-IR is a measure of hepatocyte sensitivity to insulin in the fasting state, while ISI measures whole-body insulin sensitivity following a glucose load (43).…”

Section: Discussionmentioning

confidence: 99%

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Lal¹,

Gómez²,

Calloway³

2016

JCI Insight

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“…Patients with mild disorders are usually asymptomatic; impaired glucose tolerance (IGT) is common, occurring in up to 24.1%. [8][9][10][11] Unfortunately, this represents an additional potential risk to their cardiac function. [12] Although iron overload induced DM shares certain characteristics with both type 1 diabetes and type 2 diabetes, it appears to be a separate entity with a unique pathophysiology.…”

Section: Glucose Abnormalities In Patients With Thalassemia Majormentioning

confidence: 99%

Endocrine Complications

Sanctis¹

2018

Thalassemia Reports

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“…Therefore, patients with TM and health professionals should be aware of the high incidence of glucose abnormalities in patients with thalassemia syndromes 5,7. Detecting the pre-diabetes stage is critical because prediabetes and clinical diabetes can potentially be reversed or prevented with optimum chelation treatment 5,7…”

Section: Introductionmentioning

confidence: 99%

“…Detecting the pre-diabetes stage is critical because prediabetes and clinical diabetes can potentially be reversed or prevented with optimum chelation treatment 5,7…”

Section: Introductionmentioning

confidence: 99%

The Icet-a Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients

Sanctis¹

2016

Mediterr J Hematol Infect Dis

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Iron overload in patients with thalassemia major (TM) affects glucose regulation and is mediated by several mechanisms. The pathogenesis of glycaemic abnormalities in TM is complex and multifactorial. It has been predominantly attributed to a combination of reduced insulin secretory capacity and insulin resistance. The exact mechanisms responsible for progression from norm glycaemia to overt diabetes in these patients are still poorly understood but are attributed mainly to insulin deficiency resulting from the toxic effects of iron deposited in the pancreas and insulin resistance. A group of endocrinologists, haematologists and paediatricians, members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) convened to formulate recommendations for the diagnosis and management of abnormalities of glucose homeostasis in thalassemia major patients on the basis of available evidence from clinical and laboratory data and consensus practice. The results of their work and discussions are described in this article.

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Diabetes and Glucose Metabolism in Thalassemia Major: An Update

Cited by 44 publications

References 39 publications

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

Endocrine Complications

The Icet-a Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients

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