Background/Purpose: Insulin resistance (IR) is
increased and β-cell function
impaired in rheumatoid arthritis (RA). The aim of this study was to evaluate whether treatment with tocilizumab
(TCZ) results in attenuation of IR and improvement of β-cell function.

Methods: The study
population included 31 RA pts, (mean age 53.5±11.1 yrs, RA duration 7.1±6.5 yrs, all on disease modifying antirheumatic drugs,
77.4% on steroids (8.0±2.9 mg)), without diabetes, cardiovascular diseases, and
previous treatment with biologic drugs. Disease activity was assessed using mDAS28-SE and mHAQ. Insulin
resistance was calculated using the updated-computer Homeostasis Model
Assessment (HOMA2-IR), with an algorithm to determine insulin sensitivity (%S) and β cell function (%B) from
fasting plasma glucose and specific insulin, or C peptide concentrations. We
used C peptide to calculate β cell function, as a marker of secretion, and
proinsulin as indicator of β cell dysfunction. Serum specific insulin was measured by a
sensitive ELISA and the values were logarithmically transformed (coefficient of
variation 42-55%). Association between baseline HOMA2-IR, demographics,
disease-related factors, and inflammation
markers (SE, hsCRP IL-6) was evaluated using linear regression. Changes in HOMA2-IR, HOMA2%-B, HOMA2%-IS and proinsulin concentration during TCZ therapy were assessed using a
general linear method.

Results: Baseline logHOMA2-IR was
associated with body mass index, triglycerides concentration and mHAQ
(β-coefficients [95% CI]: 2.64 [0.003,0.023; p=0.013], 2.79 [0.074,
0.500;p=0.010], and 2.082 [0.005, 0.572;p=0.046], respectively) but not with
DAS28-SE, RF or anti CCP positivity, IL-6 level, ESR, CRP, or steroids. After
12 weeks of TCZ treatment, HOMA-IR was reduced and HOMA2%-IS was improved but
did not change after 24 weeks of treatment although parameters of disease
activity (DAS28-SE, mHAQ), and inflammation markers (ESR value) continued to
decrease. Improvement of %IS did not follow better β cell function assessed
by HOMA2%-B. Importantly, proinsulin concentration was significantly reduced
after 12 weeks of TCZ, without changes further on (Table 1).

Conclusion: These data support
hypothesis that inflammation and disease activity could not fully elucidate the
presence of IR and β cell dysfunction in RA pts and that β cell
dysfunction is at least in part independent of IR.

Table 1. Changes in disease activity,
inflammation markers, HOMA2-IR, HOMA2%-B, HOMA2%-IS and
proinsulin concentration after 12 and 24 weeks
of TCZ therapy in 31 RA pts without diabetes and cardiovascular diseases.

*p<0.05;
**p<0.01; ***p≤0.001, determined by a General Linear Model