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Effect of Conditioning Regimens on Glucose Metabolism in Children Undergoing Hematopoietic Stem Cell Transplantation
Eymen Yilmaz1, Baris Malbora2, Gonul Buyukyilmaz3
1Department of Pediatrics, University of Health Sciences, Bilkent City Hospital, Ankara, Turkey.
Insights
Total body irradiation (TBI) conditioning in pediatric hematopoietic stem cell transplantation (HSCT) is linked to reduced insulin sensitivity. This finding suggests a higher risk for type 2 diabetes and cardiovascular disease in survivors, independent of obesity.
Area of Science:
- Pediatric Hematology
- Endocrinology
- Oncology
Background:
- Hematopoietic stem cell transplantation (HSCT) improves leukemia survival in children.
- Long-term adverse effects, including metabolic complications, remain a concern for survivors.
- Conditioning regimens, such as total body irradiation (TBI), may influence these outcomes.
Purpose of the Study:
- To compare the effects of TBI-based versus chemotherapy-based conditioning regimens on insulin resistance in pediatric HSCT survivors.
- To identify potential risk factors for metabolic dysfunction post-transplantation.
Main Methods:
- A prospective descriptive cross-sectional study included 76 pediatric leukemia patients undergoing HSCT.
- Patients were divided into TBI-based and non-TBI (chemotherapy-based) conditioning groups.
- Oral glucose tolerance tests (OGTT), body mass index, and serum lipids were assessed.
Main Results:
- The TBI group showed significantly higher peak and total insulin levels during OGTT.
- Insulin Sensitivity Index (ISI) was significantly lower in the TBI group, indicating reduced peripheral insulin sensitivity.
- Impaired OGTT results and metabolic changes were observed, though not significantly different between groups (p>0.05).
Conclusions:
- Total body irradiation (TBI) is a risk factor for reduced insulin sensitivity in pediatric HSCT survivors.
- This reduced sensitivity poses a risk for developing type 2 diabetes and cardiovascular disease.
- These metabolic risks can occur even in the absence of obesity.
Abstract:
Hematopoietic stem cell transplantation (HSCT) has greatly improved the survival of children with leukemia; however, long-term adverse effects remain a concern. This study aims to compare the effects of total body irradiation (TBI)-based and chemotherapy-based conditioning regimens on insulin resistance in children undergoing HSCT. Patients under 18 who underwent HSCT between April 2010 and October 2023 were evaluated. Seventy-six patients (M/F:48/28) with leukemia were included in this prospective descriptive cross-sectional study. Clinical and laboratory data, including oral glucose tolerance test (OGTT), were collected. The TBI group consisted of 45 patients with ALL (66.1%), and the non-TBI group consisted of 31 patients, including 23 with ALL and 8 with AML. The median time from HSCT to OGTT was 2.7 years (IQR, 1.8-3.8) and did not differ between the two groups. Body mass index and serum lipids, except HDL cholesterol, did not differ between the TBI and non-TBI groups. Twelve patients (26.6%) in the TBI group and 6 patients (19.3%) in the non-TBI group had impaired OGTT results (p > 0.05). All four obese patients had normal glucose tolerance. The TBI group had significantly higher peak and total insulin levels during the OGTT than the non-TBI group (p = 0.02, p = 0.02, respectively). Although HbA1c and HOMA-IR did not differ between the two groups, the Insulin Sensitivity Index (ISI) was significantly lower in the TBI group, indicating reduced peripheral insulin sensitivity (p = 0.04). TBI is a risk factor for reduced insulin sensitivity in pediatric HSCT survivors, which is a risk for type 2 diabetes and cardiovascular disease without leading to obesity.
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