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Obesity and Diabetes in Survivors
What Drives Metabolic Changes in Cancer Survivors, and How Should Obesity and Diabetes Mellitus Be Managed After Cancer?

Released: April 22, 2021

Expiration: April 21, 2022

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In this commentary, I answer questions from a symposium on late endocrine effects in cancer survivors. Slides from the symposium are also available for self-study or to use in your noncommercial presentations. 

Are there data that support adipocyte dysfunction as a driver for insulin resistance in cancer survivors treated with total body irradiation (TBI)?

There is growing interest in the role of adipocyte dysfunction in mediating the risk of metabolic disease after TBI. Clinical studies have shown that TBI-exposed survivors have higher visceral adiposity and lower lean mass despite normal body mass index (BMI), suggesting that adipose tissue deposition and function may be altered by TBI exposure. Furthermore, studies of mice treated with single-dose TBI demonstrate subcutaneous adipose tissue sensitivity to radiation, as well as decreased preadipocyte number and mature adipocyte volume. 

Our group is currently conducting a pilot study to assess adipose tissue phenotypes in survivors treated with various therapeutic modalities, including TBI. We hope this work will begin to clarify whether adipose dysfunction contributes to the development of metabolic dysfunction after cancer therapy, and especially after abdominal radiation and TBI.

Can relative insulinopenia account for some of the derangements observed in cancer survivors who develop diabetes after abdominal radiation? Have there been reports of such patients needing insulin? 

Studies of large cohorts of childhood cancer survivors have demonstrated that a subset of survivors require insulin for the treatment of diabetes mellitus after abdominal radiation. These reports, however, rely on self-reported (or physician-reported) medication use and do not include dynamic studies of β-cell function and insulin sensitivity.

Our group tried to address this gap by performing oral glucose tolerance testing in 40 nonobese, nondiabetic childhood cancer survivors previously exposed to abdominal radiation.

We found that 9 individuals had glucose derangements (n = 4 with impaired fasting glucose ≥100 mg/dL; n = 4 with impaired glucose tolerance 2-hour glucose 140-199 mg/dL; n = 1 with previously unrecognized diabetes 2-hour glucose ≥200 mg/dL). None of the relatively young participants in this study had absolute insulinopenia. It is certainly possible that relative insulinopenia accounts for some of the observed derangements in this cohort, especially as survivors age.

Should patients who develop diabetes mellitus after abdominal radiation or TBI be managed as one would manage individuals with type 2 diabetes?

Based on currently available data, patients who develop diabetes mellitus after cancer therapy should be managed in the same way as other individuals with type 2 diabetes. As we learn more about the mechanisms underlying diabetes development after cancer therapy, more tailored approaches may be warranted in this cohort. 

In cancer survivors who were exposed to TBI and have obesity, should there be a lower threshold for treating dyslipidemia or preventing atherosclerosis (eg, with low-dose aspirin)? 

At this time, there are inadequate data to support the use of medications to prevent atherosclerosis or to treat dyslipidemia at a lower threshold in individuals exposed to TBI. There are trials looking at preventive medication use in childhood cancer survivors previously treated with cardiotoxic therapy, but a broad consensus is lacking.

The TBI-exposed cohort is uniquely challenging insofar as survivors experience a high burden of metabolic dysfunction, including dyslipidemia, in the absence of obesity as defined by BMI-based criteria. Future interdisciplinary collaboration will be needed to identify the best approach for cardioprevention in this high-risk cohort.  

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