Regular and frequent blood transfusions usage in patients with β-TM has improved patients’ lifespan and quality of life. However, it contributes to chronic iron overload, sometimes causing endocrine issues, mainly DMD [13].
In our study, 27.5% of the thalassemic patients (11 patients) had IR. Patients with IR included two patients with DM (18.2%), eight patients with high fasting plasma glucose (72.7%), and one patient with regular fasting and 2 h pp plasma glucose levels (no glycemic abnormality) (9.1%).
Patients with IR had a significantly longer duration of blood transfusions and higher serum ferritin, ALT, fasting plasma insulin, fasting, and 2 h pp plasma glucose compared with those with no IR.
This study showed that fasting plasma glucose and 2 h pp plasma glucose were significantly higher in thalassemic patients than the control group (P = 0,002 and P < 0.001, respectively), similar to the study of Metwally and El-Said [14]. Moreover, IR was significantly higher in patients than in controls (P = 0.015). This is consistent with that reported in a study on Chinese children with β-TM, where IR was significantly higher in patients than controls [15]. In this study, 5% of thalassemic patients had fasting plasma glucose in the range of the provisional diagnosis of diabetes. This is similar to the Egyptian study conducted by Metwalley and El-Saied, who reported that the incidence of diabetes was 5% among studied β-TM cases [14]. This is also nearly similar to a recent study that found that the prevalence of DM in β-TM patients was 6.54% [16].
The incidence of DM in our study was higher than the overall prevalence of diabetes in Chinese thalassemic children under 18 years, which was 2% [15]. Our results were also higher than the reported incidence in the study conducted by Bhat and Periasamy, where diabetes was not diagnosed in any of the β-TM patients included in their study [17].
Our study showed that there was a significant positive correlation between HOMA-IR in β-TM patients and duration of blood transfusion and serum ferritin, in agreement with the study of Hafez et al., who reported that there was a positive correlation between serum ferritin and HOMA IR [18], and in agreement with Bhat and Periasamy, who found that there was a progressive increase in IR with the increase in the number of units transfused and age [17]. Also, in agreement with Ansari et al., who found that the association between serum ferritin values and HOMA-IR index value was highly statistically significant (P < 0.001) [19].
In this study, HOMA-IR significantly increased with the increase in ALT level. This is similar to a study done by Liang et al., which reported a significant positive correlation between HOMA-IR, the gold standard marker of IR, and age, serum ferritin, and ALT levels, suggesting that the degree of iron overload and hepatic dysfunction were responsible for the IR [15]. This study demonstrated a significant positive correlation between serum ferritin and fasting plasma insulin, fasting plasma glucose and 2 h pp plasma glucose, and HOMA-IR. This was similar to the study, which reported that the ferritin level was positively correlated with the fasting plasma glucose and 2 h pp plasma glucose [20]. This study showed a highly significant positive correlation between serum ferritin in thalassemic patients and ALT level (P = 0.001). This was in agreement with Ezzat et al., who found a significant positive correlation between serum ferritin and liver enzymes; AST (r = 0.978, P ˂0.001), and ALT (r = 0.98, P ˂ 0.001) [21]. In our study, 11 patients had IR, two of them had DM, eight patients had IFG, and one patient did not have any glycemic abnormality, suggesting that IR precedes the glycemic abnormalities (prediabetes and DM). This was similar to the study of Soliman et al., who reported that three of their adolescents with B-TM showed IR state, one of them had DM, one had prediabetes, and the third one did not have any glycemic abnormality [20]. This state of IR may overwork the beta-cell function and, in addition to iron toxicity, leads to prediabetes and DM later.
In our study, there was a significant increase in DM, and prediabetes with the increase of the duration of blood transfusion, ALT, 2 h pp plasma glucose, and HOMA-IR than those with no glycemic abnormality, and there was a highly significant increase in serum ferritin of DM and IFG (prediabetic) than those with no glycemic abnormality.
The only patient in our study who had IR with no glycemic abnormality had the youngest age, the least duration of blood transfusion, and the least serum ferritin. This might show that IR precedes prediabetes and DM, which may develop after that with age progression and increased blood transfusion duration. This highlights the importance of good observation and close monitoring of glycemic parameters of these patients. However, to confirm our results, this requires more extensive longitudinal studies rather than cross-sectional studies. This was in agreement with Metwally and El-Saied. They found that fasting and 2 h pp glucose, fasting insulin, HOMA-IR, ALT, and serum ferritin levels showed a significant increase in thalassemic patients with DM and prediabetes than patients with standard glucose tolerance [14].
In this study, there was no significant difference between patients with IR and those with no IR regarding liver span and spleen size; this was in agreement with Bhat and Periasamy, who found that the size of the liver and spleen did not correlate with any of the parameters like IR, age, ferritin, number of transfusions or glycemic indices, like fasting glucose and fasting insulin [17].
ROC curve analysis in our study showed that the duration of blood transfusion at a cut-off value ≥ 10.2 years and serum ferritin at a cut-off value ≥ 3173 ng/dl could significantly predict IR, with a sensitivity of 63.6% and 81.8% and a specificity of 69% and 82.8%, respectively. Also, ROC curve analysis showed that fasting plasma glucose at a cut-off value ≥ 115.5 mg/dl, 2 h pp glucose at a cut-off value ≥ 162.5 mg/dl, and fasting plasma insulin at a cut off value ≥ 9.13 could significantly predict IR, with a sensitivity of 81.8% and a specificity of 79.3%, 62.15%, and 72.4%, respectively. This was in disagreement with Ghergherehchi and Habibzadeh, where they found that only ALT could predict DM occurrence, unlike other variables such as serum ferritin or blood transfusion duration [22].