Increased Risk of Diabetes Mellitus Among Adult Survivors of B-Cell Non-Hodgkin Lymphoma
Authors: Chang Derek K , Park Jihye , Wan Yuan , Fraser Alison , Rowe Kerry , Snyder John , Deshmukh Vikrant , Newman Michael , Herget Kimberly , Smith Ken , Hashibe Mia , Lee Catherine J. 
Published: October 2019

Abstract

Introduction
Improvements in multi-modal therapies have increased survival rates for older adults diagnosed with B-cell Non-Hodgkin Lymphoma (B-NHL). Despite this success, B-NHL survivors are at an increased risk for developing long-term and late complications of these therapies thereby compromising survival. Several studies have reported an increased risk in diabetes mellitus (DM) among long-term survivors of Hodgkin lymphoma and pediatric cancers. However, there are limited data on the risk of DM and its risk factors in older adults following treatment for B-NHL. Using data from the Utah Population Database, we evaluated the association between treatment for B-NHL and DM risk and furthermore compared this risk to a matched Utah general population. We hypothesized that the risk of DM among B-NHL survivors would be significantly increased compared to the general population.
Methods
Adult (age >18 years at diagnosis) survivors of primary B-NHL living in Utah at the time of diagnosis between 1997-2013, without a previous diagnosis of DM, and matched (1:4) to individuals without a prior history of DM from the Utah general population for birth year, birth state, and sex were included. New DM diagnoses were identified for all-time, 0-1, 1-5, and 5-10 years following a diagnosis of B-NHL. Adjusting for sex, race, baseline body mass index (BMI), and Charlson Comorbidity Index (CCI) scores, multivariate Cox proportional hazard analysis was performed to estimate the adjusted hazard ratio (aHR) of DM in B-NHL survivors compared with that in matched non-B-NHL individuals. Risk factors for DM were evaluated, including age at diagnosis, race, sex, BMI at baseline, family history of DM, cancer stage at diagnosis, and treatment modality. The risk of developing DM during all-time, 0 to 1, 1 to 5, and 5 to 10 years follow-up after adjusting for demographic variables was analyzed by age (< 40, 40-65, and >65 years) at diagnosis of B-NHL.
Results
The study population included 3,970 B-NHL survivors and 19,821 matched individuals from the general population. At the time of diagnosis, the majority of B-NHL patients were age 60 or greater (61.4%), had diffuse large B-cell lymphoma (46%) or follicular lymphoma (26.4%), distant cancer stage (50.1%), and received chemotherapy (27.5%). DM was diagnosed in 897 (22.6%) B-NHL survivors and 3,253 (16.4%) non-B-NHL adults. The majority in both groups were male (B-NHL: 55.5%; controls: 55.5%), white (B-NHL: 97.4%; controls: 93.8%), overweight [BMI 25-29.9 kg/m2 (B-NHL: 40.7%; controls: 40.6%)] or obese [BMI ≥30 kg/m2 (B-NHL: 21.8%; controls: 18.5%)]. The risk of developing DM among B-NHL survivors compared to the control group was significantly increased over all time (HR, 1.34; 95% CI 1.24 - 1.44) and the 0 to 1 year follow-up period (HR, 1.28; 95% CI 1.15 - 1.43)(Table 1). Multivariable analysis for DM risk showed that age 40-65 years and BMI ≥25 were factors independently associated with developing DM at all-time, 0 to 1, 1 to 5, and 5 to 10 years after diagnosis of B-NHL. Male sex and a family history of DM were significantly associated with development of DM during all time, 1 to 5, and 5 to 10 year follow-up periods. Distant cancer stage at diagnosis was a significant risk factor for DM at all time and 1 to 5 years while receipt of chemotherapy only or chemotherapy with radiation were significantly associated with development of DM at 5 to 10 years after diagnosis of B-NHL (estimated aHR and CIs are shown in Table 2). There was no significant association between race and the development of DM.
Conclusion
Adult survivors of B-NHL have an overall significantly higher risk of developing DM in the first year and over all time following a diagnosis of B-NHL compared to the general population. Age 40 to 65 years and BMI ≥25 were significant risk factors for DM across all follow-up periods while treatment with chemotherapy only or chemotherapy with radiation significantly increased the risk of DM 5-10 years after diagnosis of B-NHL. Race did not appear to be a risk factor for DM but this result may reflect the homogeneity of our study population. These findings contribute important information to the existing literature regarding the risk of developing DM in adult B-NHL survivors and provide foundation for the development of screening and management guidelines for DM in the B-NHL survivor population.

Disclosures
No relevant conflicts of interest to declare.