Background It has been shown that inflammation directly influences insulin and glucose metabolism through cytokines such as TNFα and IL-6. It has also been reported that certain RA drugs such as TNF inhibitors, hydroxychloroquine, and MTX were associated with lower diabetes risk among people with RA, but it is still clinically unknown. On the other hand, it has been shown that MTX is involved in activation of intracellular AMP-kinase and promotes glucose uptake in skeletal muscle (Diabetes, 2015).
Objectives We examined medical records of patients with new RA patients complicated with glucose intolerance to measure in HbA1c, body weight, and DAS28-ESR for 6 and 12 months treated with TNF inhibitors, MTX, and the other DMARDs.
Methods Newly registered 20 RA patients complicated with glucose intolerance (HbA1c ≥5.6%) at our hospital from May 2013 to December 2015, have treated with as follows; Treatment with infliximab (1 case), golimumab (3 cases), and etanercept (2 cases) in combination with 4–12mg/week of MTX (group A: 6 cases, TNF inhibitors + MTX), MTX (4–10 mg/week) alone (group B: 8 cases MTX alone). The other DMARDs (group C: 6 cases, the other DMARDs including bucillamine (BCL) + salazosulfapyridine (SASP) + tacrolimus (TAC); 1case, BCL+SASP; 1case, BCL alone; 2 cases and SASP alone; 2 cases) had been registered. We have compared the changes of HbA1c levels, body weight, DAS 28-ESR from the beginning of the treatments and 6 and 12 months later. RA patients treated with glucocorticoid were excluded. Diabetic treatment were diet and exercise in all cases, but metformin (500 mg) and DPP4 inhibitor were used in 4 cases (Group A and C). However, each patient in Group B did not use antidiabetic agents. We analyzed these results with paired and unpaired t test using JMP12.2.0.
Results These registered RA patients with female were 60.0%. The mean age were 62.1, 53.5 and 63.8 for group A, B, and C, respectively. There were significant changes in DAS28-ESR after treatment for 6 months in group A and B, respectively (p<0.01 in group A and p<0.05 in group B).
Groups A and B showed significant improvement of DAS 28-ESR after treatment with 12 months (P<0.0001 in group A, p<0.01 in group B), but no significant difference of DAS28-ESR in group C was observed. The mean reduction in HbA1c showed a significantly decreases only in the group B (P<0.01). There were no significant differences in body weight between the each group, but slightly an increase in body weight was observed in group B. There were no significant correlations between body weight and DAS28-ESR and its changes.
Conclusions In this study, MTX was thought to contribute not only to suppress chronic inflammation but also to improve the glucose tolerance as compared with TNF inhibitors plus MTX and the other DMARDs. Further studies concerns about the interrelationship between glucose tolerance and RA treatments may require.
Sergej Pirkmajer, et al. Diabetes 2015;64:360–369.
Laura R. Rekedal, et al. Arthritis Rheum.2010;62(12):3569–3573.
Daniel H. Solomon, et al. JAMA.2011;305(24):2525–2531.
Disclosure of Interest None declared