Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction

Pappas, S. Chris; Donohue, S. M.; Denver, A. E.; Mohamed‐Ali, Vidya; Goubet, Stephanie; Yudkin, John

doi:10.1016/s0026-0495(96)90038-4

Cited by 27 publications

(31 citation statements)

References 24 publications

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“…Conflicting results have been reported for the relationship between insulin secretion and various parameters reflecting iron overload or liver cell disorder [9,21,23]. Neither serum ferritin nor hepatic iron concentration were correlated with insulin secretion in our patients.…”

Section: Discussioncontrasting

confidence: 87%

“…Recently, several studies reported a long period of insulin resistance preceding overt diabetes mellitus in thalassaemic patients [4,7,9,10,13,21,23,27]. Because of the inverse relation between insulin sensitivity and insulin secretion, insulin resistance in patients at risk for type 2 diabetes mellitus is associated with hyperinsulinaemia.…”

Section: Discussionmentioning

confidence: 99%

“…The traditional concept assumed that diabetes in patients with haemosiderosis was directly due to iron-induced damage to pancreatic b-cells resulting in insulin deficiency [20,25]. Recently, several studies suggested that overt diabetes mellitus in thalassaemic patients is preceded by a long period of insulin resistance and hyperinsulinaemia [4,7,9,13,14,21,23]. As described for type-2-diabetes mellitus, a chronic stimulation of insulin secretion might then lead to secondary b-cell failure.…”

Section: Introductionmentioning

confidence: 99%

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Insulin sensitivity and β-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test

et al. 2003

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Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin sensitivity and β-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test

et al. 2003

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“…Since the number of patients with disturbances of glucose tolerance is rather small compared to that of patients with normal glucose tolerance, the lack of difference between patients with or without glucose intolerance needs to be confirmed by studies including more affected patients. An elevation of fasting proinsulin levels and of the proportion of proinsulin-like molecules as percentage of total insulin-like molecules in thalassemic patients was also found in another group of 12 thalassemic patients [7]. In that study, however, a comparison between patients with normal, impaired or diabetic glucose tolerance was not performed.…”

Section: Discussionmentioning

confidence: 96%

“…During recent years, several studies have demonstrated that overt diabetes mellitus in thalassemic patients is preceded by a long period of insulin resistance [3, 4, 5, 6, 7]. As described for type 2 diabetes mellitus, it has been suggested that chronic stimulation of insulin secretion may lead to secondary insufficiency of pancreatic β cells.…”

Section: Introductionmentioning

confidence: 99%

Disproportionately Elevated Fasting Proinsulin Levels in Normoglycemic Patients with Thalassemia major Are Correlated to the Degree of Iron Overload

Cario¹,

Holl²,

Debatin³

et al. 2003

Horm Res Paediatr

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Objective: To analyze the secretion of the insulin precursor proinsulin in patients with β-thalassemia and its possible relation to iron overload. Methods: We assessed fasting proinsulin, insulin, C-peptide and glucose levels from 34 patients with β-thalassemia and 33 healthy controls. The correlation to age, body mass index, hepatic iron concentration, serum ferritin and serum AST was analyzed. Results: Fasting proinsulin (p < 0.002) and proinsulin-to-insulin ratio (p < 0.02) were significantly increased in patients with thalassemia irrespective of the degree of glucose tolerance. They correlated positively to serum ferritin, liver iron, patient age and serum AST (all p < 0.05). Conclusions: Disproportionately elevated proinsulin levels in thalassemic patients indicate early β-cell dysfunction due to siderosis. An additional biological significance of hyperproinsulinemia and its possible ability to predict long-term iron toxicity in these patients remain to be clarified.

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Pancreatic iron and glucose dysregulation in thalassemia major

et al. 2011

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Pancreatic iron overload and diabetes mellitus (DM) are common in thalassemia major patients. However, the relationship between iron stores and glucose disturbances is not well defined. We used a frequently sampled oral glucose tolerance test (OGTT), coupled with mathematical modeling, and magnetic resonance imaging (MRI) to examine the impact of pancreatic, cardiac, and hepatic iron overload on glucose regulation in 59 patients with thalassemia major. According to OGTT results, 11 patients had DM, 12 had impaired glucose tolerance (IGT), 8 had isolated impaired fasting glucose (IFG), and 28 patients had normal glucose tolerance (NGT). Patients with DM had significantly impaired insulin sensitivity and insulin release. Insulin resistance was most strongly associated with markers of inflammation and somatic iron overload, while disposition index (DI) (a measure of beta cell function) was most strongly correlated with pancreas R2*. Patients with DM and IGT had significantly worse DI than those with NGT or IFG, suggesting significant beta cell toxicity. One-third of patients having elevated pancreas R2* had normal glucose regulation (preclinical iron burden), but these patients were younger and had lower hepatic iron burdens. Our study indicates that pancreatic iron is the strongest predictor of beta cell toxicity, but total body iron burden, age, and body habitus also influence glucose regulation. We also demonstrate that MRI and fasting glucose/insulin are complementary screening tools, reducing the need for oral glucose tolerance testing, and identify high-risk patients before irreversible pancreatic damage. Am. J. Hematol. 87:155-160, 2012. V

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Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction

Cited by 27 publications

References 24 publications

Insulin sensitivity and β-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test

Insulin sensitivity and β-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test

Disproportionately Elevated Fasting Proinsulin Levels in Normoglycemic Patients with Thalassemia major Are Correlated to the Degree of Iron Overload

Pancreatic iron and glucose dysregulation in thalassemia major

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