Abstract
Up to 20% of adult patients with Thalassemia major (Thal) live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years) with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05) and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048). Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL), showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL) and insulin to glucose ratios at 120 min post glucose dose (p = 0.05). Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.
Highlights
Thalassemia (Thal) is a heterogeneous group of autosomal recessive disorders of limited or absent production of the alpha or beta globin chain of hemoglobin; classified according to which globin chain is deficient
Insulin values above are raw means ± SEM. These preliminary results suggest that zinc status is related to glucose homeostasis and insulin secretion in patients with transfusion dependent thalassemia
It is clear that the glucose response curve differs between patients with low circulating zinc and those with normal zinc, a difference that has not been reported previously
Summary
Thalassemia (Thal) is a heterogeneous group of autosomal recessive disorders of limited or absent production of the alpha or beta globin chain of hemoglobin; classified according to which globin chain is deficient. 9% to 19% of adult patients with transfusion dependent β-Thal major suffer from diabetes [4,5]. Diabetes is clinically characterized by hyperglycemia due to either low circulating concentrations of, or decreased sensitivity to, insulin. Patients with Thal typically exhibit β-cell or insulin insufficiency, and may develop diabetes due to toxic levels of iron in their pancreas, one of the strongest predictors of β-cell destruction [6]. It has been suggested that in this subset of patients with Thal, diabetes may be reversible, if identified early and total body iron is reduced [8]. Diabetes is a cause of significant morbidity even in historically well-chelated patients with β thalassemia who have low tissue liver iron concentrations [4].
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