Glucocorticoid administration and hyperglycemia in adults with hematological malignancies: A population-level retrospective cohort study
diabetes, glucocorticoids, steroids, Hodgkin’s, lymphoma, leukemia, cancer, chemotherapy, acute care, hyperglycemia
Objective: Hyperglycemia is a common side effect of glucocorticoids; a medication used frequently in hematological chemotherapy treatment. This study determined the association with glucocorticoid usage; new-onset diabetes, new-onset hyperglycemia, hyperglycemia; acute care utilization; and mortality. Methods: This retrospective cohort study utilized health administrative data from ICES, formerly the Institute for Clinical Evaluative Sciences. Adults aged >18 years from Ontario, Canada with a primary diagnosis of leukemia, Hodgkin’s lymphoma (HL) or non-Hodgkin’s lymphoma (NHL) were included between January 1, 2006 and December 31, 2016. Adjusted negative binomial regression or modified Poisson regression with robust variance estimation was used to describe relative risk. Cox proportional hazard models and Kaplan-Meier curves were used to derive hazard ratios and event probability Results: 19,530 individuals undergoing chemotherapy were identified. Patients with leukemia had the highest rate of new-onset diabetes, new-onset hyperglycemia and hyperglycemia: 7.1% (n=279),18.1% (n=641) and 25.4% (n=1,201) respectively, followed by those with NHL: 4.0% (n=385) vs. 10.2%, (n=923) vs. 17.9% (n=2,170) and HL: 2.8% (n=59) vs. 6.6% (n=133) vs. 10.2% (n=234). Glucocorticoid exposure was associated with an increased risk of new-onset diabetes (HR 1.29; 95% CI 1.01-1.64; p=0.04), new-onset hyperglycemia (HR 1.28; 95% CI 1.09-1.5; p=0.003, RR 1.87; 95% CI 1.03-1.83; p=0.03) and hyperglycemia (HR 1.14; 95% CI 1.02-1.28; p=0.02) in the leukemia cohort. Increased frequency of acute care utilization was noted in patients with hyperglycemia, compared to those without, during chemotherapy across all cancer cohorts: leukemia (76.3%, n=488 vs. 58.2%, n=2,610), NHL (73.9%, n=930 vs. 60.9%, n=6,599) and HL (74%, n=91 vs. 59.1%, n=1,163), and the combined (HR 1.18; 95% CI 1.09-1.27; p=<0.0001) and NHL (HR 1.16; 95% CI 1.04-1.28; p=0.007) cohorts saw an increase in mortality in patients who experience hyperglycemia. Conclusions: Hyperglycemia during and after chemotherapy is common. Patients with leukemia undergoing chemotherapy are at higher risk for hyperglycemic states. Patients with hyperglycemia were more likely to utilize acute care resources and had an increased risk of mortality. Hematological cancer protocols and guidelines should include hyperglycemia interventions such as screening, monitoring, management and patient education.