Survivors of childhood cancer—particularly those who have undergone total body irradiation in preparation for bone marrow transplant—have increased rates of hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in adolescence and young adulthood, reported Dr. Kristen Neville of the University of New South Wales, Sydney, and her associates.
The researchers assessed 248 survivors of childhood cancer who had been treated initially at Sydney Children's Hospital during 1971–2000 and had regularly attended follow-up clinics.
Overall, 18% of the survivors had developed hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus by the time they reached puberty or young adulthood. Many were asymptomatic and were diagnosed only because they were screened for this study, Dr. Neville and her associates said.
The findings suggest that a metabolic abnormality becomes established early in these individuals, and that a simple measurement of the waist-to-height ratio can be used to screen for that abnormality well before it emerges clinically years later. Early dietary and lifestyle interventions might then prevent or delay the onset of hyperinsulinemia, impaired glucose tolerance, and frank diabetes, the investigators said (J. Clin. Endocrinol. Metab. 2006;91:4401–7). The results also indicated that some survivors of childhood cancer begin showing increased abdominal adiposity and adverse lipid changes before or during puberty, even though their rates of overweight and obesity are the same as those of control subjects at that age.
At the time when the cancer survivors were evaluated for this study, in 2002–2004, their median age was 18 years, and the median interval since cancer diagnosis was 13 years; 36 subjects were prepubertal, 88 were pubertal, and 124 were young adults. The subjects were at least 2 years past their cancer diagnoses and had been disease free for a minimum of 1 year.
Patients who had undergone bone marrow transplantation accounted for more than half of those who had developed diabetes, hyperinsulinemia, or impaired glucose tolerance. This suggests that total body irradiation conditioning should be reconsidered. “If alternative conditioning therapies for bone marrow transplant can be considered without compromising survival, the risk of metabolic abnormality may be decreased,” the investigators said.
The median fasting insulin levels in the prepubertal and pubertal subjects were approximately twice those of controls. In addition, 23% of the pubertal subjects had hyperinsulinemia, impaired glucose tolerance, or diabetes mellitus, compared with none of the controls in that age group.
The prevalence of abdominal adiposity among the prepubertal and pubertal cancer survivors was double that of matched control subjects. The cancer survivors had similar body mass index values, but higher waist:height ratios. Accumulation of abdominal fat was also seen in the adult cancer survivors.
This suggests that rather than a high BMI, a waist:height ratio of 0.5 or greater “may be an early and simple clinical marker for the later development of the metabolic disturbance,” the researchers noted.