Obesity and Insulin Resistance after Chemotherapy in Patients with Acute Lymphoblastic Leukemia
Authors: Oymak Yesim , Uysal Belgin , Hilkay Karapinar Tuba , Ay Yilmaz , Ince Dilek , Demirag Bengu , Tatli Gunes Burcak , Albudak Ozcan Esin , Toret Ersin , Aydin Koker Sultan , Muminoglu Neryal , Vergin Canan , Demir Korcan 
Published: October 2019

Abstract
Background
A focus on the long-term regh side effects of cancer therapy in childhood has become of crucial importance. Exposure to chemotherapy at a young age increases vulnerability to long-term treatment-induced sequelae. We evaluated the effect of radiotherapy on obesity and insulin resistance in Acute Lymphoblastic Leukemia (ALL) patients.
Methods
We evaluated obesity and insulin resistance in patients with ALL receiving follow-up care 1-5 years after treatment (ALL-BFM 2000 protocol) at Ýzmir Dr. Behçet Uz Children’s Hospital. Patients were screened for blood glucose metabolism, lipid metabolism abnormalities, obesity, and insulin resistance.
Height, weight, body mass index, biochemical parameters (fasting blood glucose level, serum lipid profile), and insulin resistance (HOMA-IR=glucose/insulin ≥ 2,7) were calculated with the data gathered from patient files. The differences between groups which did and did not receive radiotherapy (RT) assessed with the Mann-Whitney U test in terms of the data. The differences between risk groups assessed with Kruskal-Wallis test in terms of the data.
Results
Forty-one patients, 20 (48,7%) of whom were male and of 21 (51,3%) of whom were female. The mean age of the patients was 10±3.1 years . The mean± SD duration after the last chemotherapy treatment was 3.2 ±1.2 years. Twenty of the patients received prophylactic cranial RT (12 Gy), and the others did not. There were no differences between the groups who did and did not receive RT in terms of sex, age, or duration since their last chemotherapy treatment (p>0.05). Forty-one patients 19 (46,3%) of whom were in the standard-risk group, 19 (46.3%) of whom were in the moderate-risk group, and 3 (7,4%) of whom were in the high-risk group according to risk classification of ALL-BFM 2000 protocol.
The mean value ± standard deviation (SD) of the patients' height was -0.2 ± 0.8. One patient had < -2SD height which was assessed as constitutional short stature. The mean ± SD (range) value of patients' body mass index (BMI) was 20.8 ±5 (5.1-33.7). According to BMI percentages, 24 of the patients (58.5%) were below 85p (normal), 5 (12.2%) were between 85-95p (overweight), and 12 (29.3%) were obese. The mean ± SD (range) value of BMI SD for the patients who received RT was 1.0±0.9, and it was was 1.0±0.9 (p=0.29) for the patients who did not receive RT.
All the patients had normal fasting blood glucose, but 14 (34.1%) patients had insulin resistance according to the HOMA-IR index. The mean ± SD values of the HOMA-IR index were 3.1±2.1 and 2.5±2.6 for those who did and did not receive RT, respectively (p=0.03).
The mean ± SD levels for the patients who did and did not receive RT, respectively, were as follows: trigliseride levels were 112.8±53.8 mg/dL and 81.1±27.2 mg/dL; HDL cholesterol levels were 46.7±8.9 mg/dL and 50.4±11.5 mg/dL; total cholesterol levels were 161.5±24.8 mg/dL and 151.6±21.5 mg/dL; and LDL cholesterol levels were 151.6±21.5 mg/dL and 84.1±19.4 mg/dL (p>0.05).
According to the ALL risk groups, there were no differences in terms of these parameters (p>0.05).
Conclusion
In our study, RT posed a risk for insulin resistance although there were no differences between groups in terms of obesity. The height of patients were not affected by RT. This could be because of the low RT dose and the short time interval after RT treatment. In our study, the lack of difference in the obesity rate between patients who did and did not receive RT and the higher obesity prevalence (29.3%) compared to Turkey’s general population (3.7-10.3%) suggest the contribution of chemotherapy, especially steroids with well-known effects. The low numbers of patients in risk groups, might cause the lack of differences in terms of obesity or insulin resistance.
Obesity and insulin resistance were observed in ALL patients who survived after treatment. Thus these patients should be closely monitored for obesity and insulin resistance. Early diagnosis will enable us to reduce morbidity in patients with ALL.

Disclosures
No relevant conflicts of interest to declare.