Quantification of Incident Diabetes Risk With Glucocorticoid Tx in RA

Recent glucocorticoid use contributed most to the current risk of diabetes, while doses taken more than 6 months previously did not.

Glucocorticoid (GC) use is a clinically significant and quantifiable risk factor for diabetes among patients with rheumatoid arthritis (RA). This risk is influenced by dosage and treatment duration within a 6-month period, according to data published in Arthritis & Rheumatology.

Researchers used 2 primary care databases to examine the relationship between dosage and timing of GC therapy and diabetes, and to quantify the risk of incident diabetes in RA patients treated with GC compared with nonusers.

The patient cohort consisted of 21 962 patients (1992 to 2009) from the Clinical Practice Research Datalink (CPRD), a primary care database in the United Kingdom, and 12 657 patients (1998 to 2013) from the US National Data Bank for Rheumatic Diseases (NDB). Researchers examined patient information regarding GC dosage and timing.

In the CPRD database, diabetes was defined using Read codes, at least 2 prescriptions for oral antidiabetic medication, or abnormal blood test results. In the NDB, diabetes was defined with patient self-reports. The researchers analyzed the data with time-dependent Cox models and a novel weighted cumulative dose model that accounted for dosage, duration, and timing of treatment.

The hazard ratio (HR) of current GC users compared with nonusers was 1.30 (95% confidence interval [CI]: 1.17-1.45) in the CPRD and 1.61 (95% CI: 1.37-1.89) in the NDB.

The weighted cumulative dose model revealed that more recent GC use contributed most to the current risk of diabetes, while doses taken more than 6 months previously did not influence current risk. Specifically, in the CPRD, 5 mg of prednisolone equivalent dose for the last 1, 3, and 6 months yielded HRs of 1.20, 1.43, and 1.48, respectively, compared with nonusers.

“The use of 2 data sets with distinct study designs and geographic settings adds significant validity to the findings,” the authors wrote. “Despite different populations, methods of ascertaining DM [diabetes mellitus], and definitions of exposure, the incidence of DM was nearly identical in the 2 studies, as were estimates of risk for different models of [glucocorticoid] therapy.”

Summary and Clinical Applicability

The authors explained that quantification of diabetes risk with various dosages and durations of GC therapy helps patients and physicians make informed decisions about treatment.

“Having quantified the risk of DM for any pattern of steroid use, we plan further work to examine the threshold for cost-effective DM screening in patients receiving steroids for RA,” they noted. “By using novel analytic methods with replication in a second data set, we can be increasingly confident about the quantified risks of DM conferred by this commonly used drug.”

Limitations and Disclosures

The authors note that surveillance bias could not be controlled for in this study. Researchers measured the frequency with which blood glucose was measured in patients exposed to GC and those not exposed in the CPRD, and found that the frequency was 406 per 1000 patient-years in those exposed to GCs and 289 per 1000 patient-years in those never exposed.

The increased frequency of tests was a combination of surveillance bias and testing secondary to symptoms, according to researchers, but it is not possible to determine whether blood tests in the CPRD are screening tests or are performed because of clinical suspicion.

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Movahedi M, Beauchamp ME, Abrahamowicz M, et al. Risk of incident diabetes mellitus associated with the dosage and duration of oral glucocorticoid therapy in patients with rheumatoid arthritis. Arthrit Rheum. 2016;68(5):1089-1098.