High incidence of glucocorticoid-induced hyperglycaemia in inflammatory bowel disease; metabolic and clinical predictors identified by machine learning
Authors: McDonnell Martin , Harris Richard J , Borca Florina , Mills Tilly , Downey Louise , Dharmasiri Suranga , Patel Mayank , Zaré Benjamin , Stammers Matt , Smith Trevor R , Felwick Richard , Cummings Fraser , Phan Hang T.T. , Gwiggner Markus 
Published: June 2020

Background

Glucocorticosteroids (GC) are long-established, widely used agents for induction of remission in inflammatory bowel disease (IBD). Hyperglycaemia is a known complication of GC treatment with implications for morbidity and mortality. Published data on prevalence and risk factors for GC-induced hyperglycaemia in the IBD population are limited. We prospectively characterise this complication in our cohort, employing machine-learning methods to identify key predictors of risk.

Methods

We conducted a prospective observational study of IBD patients receiving intravenous hydrocortisone (IVH). Electronically triggered three times daily capillary blood glucose (CBG) monitoring was recorded alongside diabetes mellitus (DM) history, IBD biomarkers, nutritional and IBD clinical activity scores. Hyperglycaemia was defined as CBG ≥11·1mmol/L and undiagnosed DM as HbA1c ≥48 mmol/mol. Random Forest regression models were used to extract predictor-patterns present within the dataset.

Findings

94 consecutive IBD patients treated with IVH were included. 60% (56/94) of the cohort recorded an episode of hyperglycaemia, including 57% (50/88) of those with no prior history of DM, of which 19% (17/88) and 5% (4/88) recorded a CBG ≥14mmol/L and ≥20mmol/L, respectively. The Random Forest models identified increased CRP followed by a longer IBD duration as leading risk predictors for significant hyperglycaemia.

Interpretation

Hyperglycaemia is common in IBD patients treated with intravenous GC, therefore CBG monitoring should be included in routine clinical practice. Machine learning methods can identify key risk factors for clinical complications. Physicians should consider steroid-sparing strategies in high-risk patients such as those with high admission CRP or a longer IBD duration. There is an emergent case for research to explore steroid-free treatment regimens for hospitalised patients with severe IBD flares.

Evidence before this study

Glucocorticosteroids (GC) are long-established induction agents in the management of inflammatory bowel disease (IBD). They are recommended first-line therapy in consensus guidelines and prescribing remains widespread, with an estimated 30% of IBD patients exposed annually. Hyperglycaemia is a known complication of GC and has been linked to increased length of hospital stay, morbidity and mortality. Small case series of GC treated medical patients suggest a higher risk of hyperglycaemia in the hospitalised population but have suffered from a lack of systematic blood glucose monitoring.

Added value of this study

This is the first study utilising prospective, systematic monitoring of capillary blood glucose (CBG) to determine the frequency of hyperglycaemia in a GC-treated hospitalised IBD population. We report that more than half of IBD patients without prior diabetes mellitus treated with intravenous hydrocortisone (IVH), will develop hyperglycaemia (CBG ≥11·1mmol/L). Random Forest regressors pinpointed CRP and IBD duration as the strongest predictor of this adverse outcome.

Implications of all the available evidence

Hyperglycaemia is a common complication of IVH therapy in hospitalised IBD patients, particularly in those with high inflammatory burden. The monitoring and management of this complication, which has potential implications for the morbidity, mortality and subsequent risk of diabetes diagnosis should become part of routine clinical practice.