Childhood cancer survivors treated with total body or abdominal radiotherapy have an increased risk for insulin resistance and diabetes, according to a new pilot study.
These findings follow on from a 2012 study conducted by Dr. Florent de Vathaire et al, published in The Lancet, that reported children and young adults with cancer who are exposed to abdominal radiation are more likely to develop both insulin and non-insulin dependent diabetes. Radiotherapy is a treatment that involves destroying cancer cells with radiation.
In this new study, researchers from the Pediatric Long-term Follow-up Program, Memorial Sloan Kettering Cancer Centre, New York City, analysed cancer survivors who were youngsters at the time of radiation exposure.
Lead author Dr. Danielle Friedma, MD, said: “We wanted to (…) explore whether there is an autoimmune component involved in the development of diabetes. Our preliminary data suggest abnormal glucose and insulin dynamics are indeed prevalent in childhood cancer survivors who are exposed to abdominal radiation.”
The average age of the 26 study participants at the time of radiation exposure was 3.3 years, while their median age during the study was 14.4 years. The patients had been off cancer treatment for a minimum of two years at baseline.
20 patients received a primary diagnosis of neuroblastoma, a rare cancer that mostly affects young children. 24 patients received 20-29 Gv of radiation to the pancreas, one received 10.8 Gv and another received 36 Gv. At study baseline, three survivors were overweight but none was obese – which holds significance as obesity is a leading cause of type 2 diabetes.
All participants took a two-hour glucose tolerance test, had their HbA1c levels and insulin resistance measured, and were evaluated for autoantibodies (insulin autoantibodies, islet cell autoantibodies and glutamic acid decarboxylase) which are typically present in people with type 1 diabetes.
Nine of the 26 patients had abnormal glucose or insulin homeostasis, but Friedman added: “Importantly, none had overt diabetes, none had autoantibodies, and none had an abnormal A1c level. Looking at a breakdown, we can see that there is no discreet pattern of abnormal levels.”
This lack of pattern was evidenced by two of the four participants with impaired glucose tolerance having normal insulin homeostasis, while two had defects in insulin secretion.
Friedman explained: “When we looked at the Matsuda Index (used to measure insulin resistance) in relation to time since radiotherapy, we saw an interesting trend of increasing insulin resistance with increasing time since radiotherapy.
“These derangements are apparent at a very young age, even in the absence of clinical obesity. Loss of insulin sensitivity and defects in secretion may play a pivotal role in mediating this process.”
Friedman also reported that the specific underlying mechanism of this link with diabetes has yet to be determined, but is hoping to recruit adult patients, who finished radiotherapy a long time ago, for new trials.
The findings were presented at the Cancer Survivorship Symposium Advancing Care and Research.

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