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. 2017 Oct 17;19(1):229.
doi: 10.1186/s13075-017-1431-9.

Incretins in patients with rheumatoid arthritis

Beatriz Tejera-Segura  1 , Raquel López-Mejías  2 , María Jesús Domínguez-Luis  1 , Antonia M de Vera-González  3 , Alejandra González-Delgado  2 , Begoña Ubilla  2 , José M Olmos  4 , José L Hernández  4 , Miguel A González-Gay  5   6   7   8 , Iván Ferraz-Amaro  9
Affiliations

Incretins in patients with rheumatoid arthritis

Beatriz Tejera-Segura et al. Arthritis Res Ther. .

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 (β coefficient 46, 95% CI 6-87, p = 0.026) and Clinical Disease Activity Index (β coefficient 7.74, 95% CI 1.29-14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with β-cell function (HOMA2 of β-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.

Keywords: Incretins; Insulin resistance; Rheumatoid arthritis.

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Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the institutional review committees at Hospital Universitario de Canarias and Hospital Universitario Marqués de Valdecilla (both in Spain), and all subjects provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Meal test curves of glucose, insulin, C-peptide, gastric inhibitory polypeptide, and glucagon-like peptide 1 concentrations in patients with rheumatoid arthritis and control subjects
See this image and copyright information in PMC

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