Glucose metabolism and body composition in young adults treated with TBI during childhood

Abstract

After SCT in childhood, survivors may develop disorders of glucose metabolism. The role of obesity is controversial. We measured insulin sensitivity using the homeostasis model assessment (HOMA) and the frequently sampled i.v. glucose tolerance test (FSIVGTT), as well as body composition using dual-energy X-ray absorptiometry in 18 young adults median 18.2 years after SCT and compared them with matched controls. We also measured growth hormone (GH) secretion, and levels of leptin and adiponectin. HOMA showed insulin resistance in eight patients (44%), as opposed to none of the controls (P=0.008) and FSIVGTT showed a decreased sensitivity index in the patients (2.98 vs 4.54 mU/L/min, P=0.042). Dual energy X-ray absorptiometry showed a higher percentage fat mass in the patients (34.9 vs 24.3%, P=0.011), which correlated inversely with the sensitivity index (r=-0.52, P=0.032). The patients had a lower peak value of GH (GH(max) 9 vs 20.7 mU/L, P=0.002). Time post SCT correlated with percentage fat mass and inversely with GH(max). The patients had higher levels of leptin and lower levels of adiponectin, even after adjustment for fat mass. We propose that the decreased insulin sensitivity may primarily be explained by the adverse body composition, which may owe to long-standing GH deficiency.

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Cardiovascular Disease and Associated Risk Factors Working Group Report

“…The prevalence of post- HCT T2DM ranges between 3.3–17%, 13–15, 40, 43, 59, 60 rates that are higher than those observed in siblings (7.6% vs. 3.1%) 14 or age/gender matched adults from the general population (14.3% vs. 11.7%, p=0.04). 43 Diabetes also occurred sooner than expected in HCT survivors when compared to matched controls from the general population.…”

The influence of antineoplastic treatment on the weight of survivors of childhood cancer

“…BMI tended to be lower in the survivor group due to reduced lean body mass, but their higher percentages of fat mass were associated with a decrease in insulin sensitivity. 40 In addition to the HSCT itself, TBI as a preparative therapy for HSCT has been described as playing an essential role in the genesis of IR, as was pointed out by a large multicenter study that included adult and pediatric survivors of transplantation. The risk of developing type 2 diabetes mellitus was three times higher in patients who underwent HSCT, and this risk was associated with TBI.…”

Cardiovascular Risk Factors in Survivors of Childhood Hematopoietic Cell Transplantation Treated with Total Body Irradiation: A Longitudinal Analysis

“…8 Others have similarly demonstrated an increased risk of metabolic derangements in individuals exposed to TBI. 13, 14, 17, 18, 26, 27 …”