FROM RHEUMATOLOGY
The risk for developing diabetes mellitus among patients with systemic lupus erythematosus declined significantly with increasing use of hydroxychloroquine in a retrospective cohort study of a national health insurance database in Taiwan.
This population-based cohort study is the first to demonstrate that hydroxychloroquine (HCQ) reduces the risk of diabetes in a dose-dependent manner in systemic lupus erythematosus (SLE) patients. In previous research, HCQ use has been shown to improve insulin sensitivity in SLE patients, and in rheumatoid arthritis patients, longer duration of HCQ treatment (> 4 years) has been shown before to have the greatest effect on lowering the incidence of diabetes, according to Dr. Der-Yuan Chen of Taichung (Taiwan) Veterans General Hospital and his associates.
The investigators analyzed the first year of medication use in 8,628 patients with SLE in the National Health Insurance Research Database of Taiwan during 2001-2008, excluding those with less than 3 years of follow-up data and comorbid diagnoses of RA, psoriasis, or diabetes (Rheumatology [Oxford] 2015 Jan. 12 [ doi:10.1093/rheumatology/keu451 ]).
The patients’ mean age was 37 years, and 88% were female. The patients who had used HCQ were significantly older (49 years vs. 37 years) and a greater proportion had taken glucocorticoids (92% vs. 73%). Those who had taken HCQ had significantly lower rates of hyperlipidemia, hypertension, stroke, and renal disease.
The effect of HCQ on diabetes risk became apparent in patients with an average daily glucocorticoid dose equivalent to 10 mg prednisolone or greater. That glucocorticoid dose was associated with increased diabetes risk (hazard ratio, 2.29; 95% confidence interval, 1.34-3.93), but a cumulative dose of 129 g HCQ or greater (equal to 200 mg/day for 1.8 years) reduced the risk of diabetes (HR, 0.26; 95% CI, 0.18-0.37), compared with those who did not take the drug. There was no significant relationship between HCQ use and incident diabetes for those who had a cumulative dose of less than 129 g (HR, 1.13; 95% CI, 0.81-1.59).
Patients who took both an average daily glucocorticoid dose equivalent to at least 10 mg prednisolone and a cumulative dose of less than 129 g HCQ had a higher diabetes risk than did those taking a smaller prednisolone dose, whereas those who took at least 129 g HCQ had a reduced risk of diabetes despite taking high-dose glucocorticoids.
Hazard ratios for diabetes ranged from 0.10 to 0.41 among different groupings of patients who took at least 129 g HCQ, according to age, use of glucocorticoids or disease-modifying antirheumatic drugs, and presence of comorbidities.
The investigators noted that “there are substantial differences in the clinical characteristics of SLE patients with and without HCQ use … [that] may reflect the discrepancy in lupus disease activity between the two groups.” The patients who had used HCQ were significantly older (49 years vs. 37 years) and a greater proportion of them had taken glucocorticoids (92% vs. 73%).
Those who had taken HCQ had significantly lower rates of hyperlipidemia, hypertension, stroke, and renal disease. HCQ users also took more methotrexate, sulfasalazine, and azathioprine, but less cyclophosphamide, than did those without HCQ use.
While the greater use of cyclophosphamide by HCQ nonusers may indicate more frequent lupus renal involvement and potentially bias them to increased risk of diabetes because of disease activity and chronic inflammation’s effect on insulin resistance, the greater cumulative glucocorticoid dose taken by HCQ users also can predispose to the development of diabetes, the authors said.
The study is limited in its ability to tease out the contributions of clinical characteristics between HCQ users and nonusers, because the patients’ lupus disease severity and laboratory data are unknown, and treatment data were recorded only from the first year. There was also a lack of data on lifestyle, body-mass index, and family history, the investigators said.
The study had no specific funding. The authors declared having no conflicts of interest.
