Study of insulin secretion and insulin resistance in thalassemia patients with iron overload

الملخص EN

Introduction and aim of the work : Thalassemia Major is an autosomal recessive disease causing deficient synthesis of β globin chain of Hemoglobin A.

Homozygote for beta Thalassemia suffer from hemolysis, ineffective erythropoiesis and extramedullary hemopoiesis.

Patients with Thalassemia Major survive on lifelong regular blood transfusion, resulting in iron overload This in turn causes liver cirrhosis, cardiomyopathy, hypogonadism and diabetes.

Several studies found significantly high incidence of diabetes in Thalassemia patients.

In the present study, we sought to explore the elements of glucose tolerance, namely, insulin resistance and insulin secretion in that patient group.

Subjects and Methods : We studied 30 patients with Thalassemia Major aged 18-40 years and 10 age and sex matched healthy controls.

Only those who tested negative for HCV and HBV were included.

All subjects underwent full history taking and clinical examintation.

Oral glucose tolerance test was performed during which insulin response was measured.

HOMA index and ISI were calculated to represent insulin sensitivity while δIns30 represented early insulin response and AUC total insulin response.

Serum ferritin was measured to represent iron stores.

Complete blood counts and liver function tests were performed to all participating subjects.

Results : 12/30 of Thalassemia patients had normal fasting serum glucose and normal glucose tolerance.

4 / 30 had Impaired Fasting glucose (IFG), 10 / 30 had Impaired Glucose Tolerance (IGT) and 4 / 30 had Diabetic OGTT.

All control subjects had normal fasting glucose and normal glucose tolerance.

Thalassemia patients had significantly higher HOMA-IR (5.6 ± 5.4 vs.

1.54 ± 0.26, p < 0.001) and significantly lower ISI (5.85 ± 6.2 vs.

8.7±3.6, p < 0.05) indicating that they were more insulin resistant than control subjects.

At the same time, Thalassemia patients had worse indices for beta cell function ; lower early phase of insulin secretion [δIns30] (22.5 ± 7.1 vs.

48 ± 8.6, p < 0.001) and non-significantly lower total insulin response during OGTT [AUC] (94.3 ± 31.9 vs.

151 ± 46.5, p > 0.05).

Serum ferritin was the strongest independent variable in multiple regression analysis when the dependent variable was HOMA-IR (β = 0.88, p < 0.001), ISI (β = 0.47, p < 0.05) and AUC of total insulin secretion (β = 0.06, p < 0.001).

Conclusion : patients with Thalassemia Major suffer a combined defect in insulin sensitivity and insulin secretion, the former being more pronounced.

This predisposes them to glucose intolerance and diabetes.

Those complications would further undermine their health and longevity.

Early initiation and intensification of chelation therapy would protect against deterioration of glucose tolerance.