SAT0095 Incretins-insulin axis in patients with rheumatoid arthritis

Abstract

BackgroundRheumatoid arthritis (RA) patients have higher levels of resistance to the action of insulin (IR) compared to healthy subjects.The “Incretin effect” consists in a greater release of insulin by the pancreas when there is a gastrointestinal glucose stimulation, compared to an intravenous stimulation. It is known that this effect is altered in patients with IR.ObjectivesTo determine if the incretins-insulin axis is altered in patients with RA and if this correlates to IR in patients with RA, as well as if it is explainable by certain features of the disease.MethodsCross-sectional study that includes 361 non-diabetic individuals, 151 patients with RA and 210 controls. Serum levels of insulin, C-peptide, Amylin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP) and dipeptidyl peptidase 4 (DPP-4) were analyzed in patients and controls. Indexes of resistance and sensitivity to insulin activity were determined by HOMA2.A “meal test” consisting on the intake of 500 kcal was performed to a subset of 10 patients and 10 controls, in order to determine the postprandial curves of glucose, insulin, C-peptide, GLP-1 and GIP. Differences between patients and controls as well as the relationship of selected characteristics of the disease with the baseline and postprandial levels of incretins were analyzed using multivariate regression. During the meal test, areas under the curve (AUC), maximum concentrations and the minutes of response were compared between patients and controls. This study was approved by the Clinical Trial Committee of the University Hospital of the Canary Islands.ResultsPatients with RA showed, at baseline and after multivariate adjustment, higher levels of insulin (9.8±6.5 vs 13.0±13.4 U/ml, p=0.05), C-peptide (1.53±0.77 vs. 3.37±2.94 ng/ml, p=0.00), GLP-1 (0.49±1.28 vs. 0.71±0.22, p=0.00) and GIP (0.37±0.40 vs. 1.78±0.51, p=0.00). Similarly, IR indexes such as HOMA2-IR and HOMA2%B, built with insulin or Cpeptide, were higher in patients with RA compared to controls. Patients with RA, showed significantly lower levels of DPP-4 (811±459 vs. 696±301 ng/ml,p=0.02) after multivariate analysis. Amylin levels did not differ between patients and controls. Both C-reactive protein (beta coefficient 0.54,95% CI 0.16–0.96, p=0.013) and Erythrocyte Sedimentation Rate (beta coef. 0.01,0.00–0.01, p=0.033) showed a positive relationship with HOMA2%B and GIP levels, respectively. The presence of anti-cyclic citrullinated peptide antibody (beta coef. 157 CI 58–256, p=0.002) and the levels of disease activity measured by DAS28 (beta coef. 46,CI 6–87, p=0.026) and CDAI (beta coef 1.27 (0.28–2.26), p=0.012) showed a positive relationship with the levels of DPP-4. Patients with RA showed Pearson correlation coefficient of incretines, DPP-4 with insulin, C peptide and IR lower compared to control group. After the meal test patients with RA exhibited an AUC of glucose and GIP greater than controls and a slower C-Peptide response time (75 vs. 30 minutes, p=0.029).ConclusionsIncretins-insulin axis is alter...