Background/Purpose: Incretins hormones have been found to be a function of glucose tolerance in normal subjects, individuals with impaired glucose tolerance and patients with type 2 diabetes. Similarly, chronic inflammation, and rheumatoid arthritis (RA), is associated with an insulin resistance (IR) phenomenon, a well-known risk factor for cardiovascular diseases. The aim of the present study was to examine whether incretins hormones are disrupted in RA patients and if they are related with the insulin resistance (IR) that these patients express.

Methods: Cross-sectional study that encompassed 361 non-diabetes individuals; 151 patients with RA and 210 age- and sex-matched controls. IR by homeostatic model assessment (HOMA2), insulin, C-peptide, amylin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and dipeptidyl peptidase 4 (DPP-4) soluble form and lipoproteins serum concentrations, were assessed in patients and controls. A multivariable regression analysis, adjusted for IR related factors, was performed to evaluate the differences between patients and controls in incretins hormones and how these were related to inflammation and IR in patients and controls.

Results: RA patients, compared to controls, disclosed higher levels of HOMA-IR (2.49 ± 2.35 vs. 1.13 ± 0.58 vs, p=0.00), insulin (13.0 ± 13.4 vs. 9.8 ± 6.5 U/ml, p=0.04) and C-peptide (3.37 ± 2.94 vs. 1.53 ± 0.77 ng/ml, p=0.00). These differences remained significant after adjustment for age, sex, waist circumference, dyslipidemia, statins, antihypertensive treatment and cholesterol levels. Similarly, amylin showed superior serum levels in RA patients in the univariate analysis, however, after adjusting for confounders this relation was lost. Incretins, GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p=0.00) and GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p=0.00), were higher in RA patients after multivariable analysis. Contrary, DPP4 was found to be down regulated in RA patients after adjusting for IR related factors (811 ± 459 vs. 696 ± 301 ng/ml, p=0.02). While DDP-4 was correlated with disease activity through DAS28 (r=0.18, p=0.03), DAS28-PCR (r=0.5, p=0.08) and CDAI (r=0.20, p=0.01), neither insulin, C-peptide, incretins (GLP-1 and GIP) nor amylin were found to be associated with disease activity. DPP4 serum levels were significant and negatively associated with HOMA-IR-C-peptide index (beta coef -0.03 [-0.05–0.01 ng/ml], p=0.01) in the entire sample. Interestingly, the addition of RA as an interaction term in this relation disclosed a significant association (interaction p=0.04). Patients and controls in the higher HOMA-IR-C-peptide quartile (#4) disclosed different levels of GLP-1 (mean difference 0.4 [0.3-0.5] ng/ml, p=0.00), GIP (1.7 [1.4-2.0] ng/ml, p=0.00) and DPP-4 (-220 [38-402] ng/ml); showing, therefore, a different relation of IR indexes with these molecules between patients and controls.

Conclusion: Incretin axis is disrupted in non-diabetic RA patients. These defects may participate to the development of IR in RA or arise as a consequence of IR and/or other metabolic manifestations of RA itself.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incretin-axis-in-non-diabetic-rheumatoid-arthritis-patients/