FRI0056 NESTED CASE-CONTROL STUDY : ASSOCIATED FACTORS WITH INSULIN RESISTANCE IN A RHEUMATOID ARTHRITISINCEPTION COHORT
Authors: Sara Manrique Arija, Natalia Mena-Vázquez, Inmaculada Ureña, F. Gabriel Jiménez-Núñez, Clara Fuego-Varela, Antonio Fernandez-Nebro
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Objectives</h3> To asses insulin resistance (IR) in patients with rheumatoid arthritis (RA) and compare it with healthy controls and to analyze the association between the accumulated inflammatory burden in patients with RA and IR. <h3>Methods</h3> Design: Nested case-control study. Population: consecutive RA-patients (ACR/EULAR 2010 criteria), &gt;16 years, selected from a prospective inception cohort (diagnosis of RA between 2007 and 2011). Patients with Diabetes Mellitus (according to ADA 2010 criteria) were excluded. Controls: sex- age and BMI -matched controls were collected from a health center in our hospital area. Protocol: Cases and controls were evaluated by a rheumatologist. Clinical data of disease activity (RA patients), analytical values and oral glucose tolerance test (OGTT) were determined. Main outcome: IR measured by the homeostasis model for insulin resistance (HOMA-IR) (IR&gt; 2.29 μU*mmol/ml). Secondary outcome: IR measured by quantitative insulin sensitivity check index (QUICKI) (&lt;0.337μU*mmol/ml) and by the homeostatic model assessment of β-cell function (HOMA ß).Variables: Demographic, clinical-analytical variables, Disease Activity Score of 28 joints (DAS28-ESR), Health Assessment Questionnaire (HAQ), BMI (according to OMS classification) and glucose and insulin before and after OGTT values. Statistical analysis: Descriptive and paired T-test or Chi-square test followed by Multivariate Linear Regression in RA patients (Dependent variable: HOMA-IR). <h3>Results</h3> Two hundred subjects were studied, 31 of them were excluded after OGTT. Finally 169 subjects were included; 89 RA and 80 controls. The mean age of patients with RA was 56.6(±10.9) years. Most of them were women (75.3%), with seropositive (FR 82.0% y ACPA 75.3%) and erosive (61.1%) RA. The average duration of the disease was 98 months (8.1 years). The delay in the diagnosis of RA was 10.9 months (5.4 - 25.6) with a mean DAS28 index since the beginning of the disease of 3.11 (0.8). Differences between clinical characteristics and in relation to IR between cases and controls are shown in Table 1. No significant differences in the proportion of subject with IR in cases and controls were observed and 28.1% of patients with RA had IR. Of the 25 patients with IR, the majority, 68%, presented a DAS28 score&gt; 3.2 (moderate-high activity index). In multivariate analysis, the independent variables associated with IR in patients with RA were: Obesity [OR=6.01; β=1.795 (p=0.002), disease activity (OR=2.77; β=1.021 [p=0.009]]) Il-1β (OR=1.59; β=0.464 (p=0.024)). This model would explain 37.5% of the variability of the IR (R<sup>2</sup>=0.375). <h3>Conclusion</h3> We did not find an increased IR in patients with RA compared with healthy controls, which may be due to adequate treatment and good control of inflammatory activity in the most of patients with RA. Obesity, inflammatory activity (measured by mean DAS28 index) and IL-1 β were the predictors of IR in patients with RA in our study. <h3>References</h3> [1] Insulin resistance and levels of adipokines in patients with untreated early rheumatoid arthritis. Manrique-Arija S, et al. Clin Rheumatol. 2016;35(1):43-53. [2] Abnormal Glucose Metabolism in Rheumatoid Arthritis. Pi H1, Zhou H1, Jin H1, et al. Biomed Res Int. 2017;2017:9670434. [3] Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients. Castillo-Hernandez J. Rev Bras Reumatol Engl Ed. 2017;57(4):320-329. <h3>Acknowledgement</h3> I thank the Rheumatology Spanish Society for Grant support in 2015 -2017 for this work. <h3>Disclosure of Interests</h3> Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Natalia Mena-Vázquez: None declared, Inmaculada Ureña : None declared, F. Gabriel Jiménez-Núñez: None declared, Clara Fuego-Varela: None declared, Antonio Fernandez-Nebro: None declared