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Hyperinsulinemia in children and adolescents after bone marrow transplantation
R Lorini1, L Cortona, A Scaramuzza
1Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Italy.
Insights
Pediatric patients treated with bone marrow transplant (BMT) show higher insulin levels and C-peptide responses, suggesting insulin resistance, particularly after total body irradiation (TBI). These findings indicate potential long-term metabolic effects of BMT in children.
Area of Science:
- Endocrinology
- Pediatric Oncology
- Hematology
Background:
- Bone marrow transplantation (BMT) is a critical treatment for various pediatric hematologic malignancies and anemias.
- Patients undergoing BMT often receive intensive therapies including chemotherapy and radiation, which may have long-term effects on endocrine function.
- Pancreatic beta-cell function is crucial for glucose homeostasis and can be affected by these treatments.
Purpose of the Study:
- To evaluate pancreatic beta-cell function in pediatric patients following autologous or allogeneic BMT.
- To investigate the impact of different radiation modalities (total body irradiation [TBI] and thoracoabdominal irradiation [TAI]) on beta-cell function.
- To assess for potential insulin resistance in these patients.
Main Methods:
- Studied 34 pediatric patients (5-18 years) with leukemia, lymphoma, or aplastic anemia who underwent BMT.
- Assessed fasting blood glucose (FBG), HbA1C, insulin and islet cell antibodies (IAA/ICA), first-phase insulin response (FPIR), insulinemia/glycemia (I/G) ratio during IV glucose tolerance test (GTT), and C-peptide response post-glucagon.
- Compared results with 21 age- and sex-matched controls and stratified patients based on radiotherapy received (TBI, TAI, or none).
Main Results:
- All patients had normal FBG and HbA1C levels.
- Patients exhibited significantly higher insulin levels (I/G ratio, FPIR) and C-peptide responses compared to controls.
- Patients who received TBI showed significantly higher I/G ratio, FPIR, and C-peptide response compared to those who received TAI, no irradiation, or controls.
Conclusions:
- Pediatric patients post-BMT demonstrate elevated insulin and C-peptide levels despite normal glycemia, suggesting a state of insulin resistance.
- Total body irradiation (TBI) appears to exacerbate this insulin resistance.
- Long-term metabolic monitoring for insulin resistance is warranted in pediatric BMT survivors, especially those who received TBI.
Abstract:
We report 34 patients (aged 5-18 years) with acute (n = 26) or chronic (n = 1) leukemia, non-Hodgkin's lymphoma (n = 3) or severe aplastic anemia (n = 4) evaluated for pancreatic beta-cell function 9 months to 10.2 years after autologous (n = 19) or allogeneic (n = 15) BMT. Before BMT, all patients received cytotoxic drugs, combined with total body irradiation (TBI) in 24 cases or thoracoabdominal irradiation (TAI) in 4 children. Patients were investigated for fasting blood glucose (FBG), HbA1C, anti-insulin (IAA) and islet cell antibodies (ICA), first-phase insulin response (FPIR) and insulinemia/glycemia (I/G) ratio on i.v. glucose tolerance test (GTT) and C-peptide response after glucagon 1 mg i.v. Results were compared with those obtained in 21 age- and sex-matched controls. None of the patients or controls had IAA and/or ICA. FBG and HbA1C were normal in all children. In the patients, glycemia on i.v. GTT was similar to controls whereas insulin levels I/G ratio and FPIR were significantly higher in patients than in controls, as well as C-peptide levels. We divided the patients on the basis of the radiotherapy into group I with TBI (n = 18), group II with TAI (n = 4) and group III who were not irradiated (n = 4). The I/G ratio, FPIR on i.v. GTT and C-peptide response were significantly higher in group I compared with the other two groups and controls. The increased insulin and C-peptide levels in our patients with normal glycemia might be interpreted as a state of insulin resistance, more evident in patients who received TBL.