Abstract: Background: The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis
(RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are
disrupted in patients with RA and if they are related to the IR found in these patients.
Methods: We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA,
and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide
(GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were
assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control
subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules
between patients and control subjects.
Results: Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case
for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These
differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity
Score in 28 joints with erythrocyte sedimentation rate (? coefficient 46, 95% CI 6?87, p = 0.026) and Clinical Disease
Activity Index (? coefficient 7.74, 95% CI 1.29?14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively
correlated with ?-cell function (HOMA2 of ?-cell production calculated with C-peptide) in patients but not in control
subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC
for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response.
Conclusions: The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA.
Fuente: Arthritis Research & Therapy, 2017, 19, :229
Publisher: BioMed Central
Year of publication: 2017
No. of pages: 11
Publication type: Article
DOI: 10.1186/s13075-017-1431-9
ISSN: 1478-6354,1478-6362
Spanish project: RD12/0009 ; RD12/0009/0013