Background/Purpose:

Studies have demonstrated a negative association between high body mass index (BMI) and development of rheumatoid arthritis (RA) in men, and a neutral or positive association in women. This may reflect effects of body fat distribution and related metabolic pathways on the risk of RA. The purpose of the present study was to investigate the impact of oral glucose tolerance on the risk of future development of RA.

Methods:

Between 1974 and 1992, subjects (n=33346; 22444 men and 10902 women) from a defined catchment area were included in a Preventive Medicine Program (PMP). Information on life style factors was obtained using a self-administered questionnaire. A standard oral glucose tolerance test (OGTT) was performed after an overnight fast. From this population, we identified individuals who developed RA after inclusion by linking the PMP register to the local community based RA register and to local and national patient administrative databases. In a structured review of the medical records, patients were classified according to the 1987 American College of Rheumatology criteria for RA. Four controls for each validated case, matched for sex, year of birth and year of screening, who were alive and free of  RA when the index person was diagnosed with RA, were selected from the PMP register. The impact of the 2-hour OGTT glucose level on the risk of RA was examined in conditional logistic regression models.

Results:

Two hundred and ninety patients [151 men and 139 women; median time from inclusion to RA diagnosis 12 years (interquartile range 8–18, range 1-28); mean age at diagnosis 60 years] were diagnosed with RA and fulfilled the ACR criteria after inclusion in the PMP. An OGTT was performed in 177 cases (104 men, 73 women) and 708 controls (413 men, 295 women). Fasting glucose levels were similar in cases and controls (mean 4.91 vs 4.90 mmol/l). Cases with a diagnosis of RA during the follow-up had lower 2-hour OGTT glucose levels at baseline compared to controls [mean 5.58; standard deviation (SD) 1.76 vs. 6.03 (SD 1.77) mmol/l; OR 0.72 per SD; 95 % confidence interval (CI) 0.58-0.89)]. Impaired glucose tolerance (2-hour OGTT glucose level ≥ 7.8 mmol/l) was less frequent in pre-RA cases compared to controls (9.0 % vs. 15.1 %; p=0.04). The association between lower 2-hour OGTT glucose levels and subsequent development of RA remained significant in separate multivariate analyses adjusted for smoking (p=0.01) or socio-economic status (p=0.04).  In analyses stratified by sex, the estimated impact of 2-hour OGTT glucose was similar in men (OR 0.71 per SD; 95 % CI 0.54-0.92) and women (OR 0.73 per SD; 95 % CI 0.51-1.05). Two-hour OGTT glucose levels were correlated with BMI in men (r=0.22; p<0.001) and, to a lesser extent, in women (r=0.13; p=0.02). In analysis adjusted for BMI, a lower 2-hour glucose level remained a significant predictor for RA in men (OR 0.75 per SD; 95 % CI 0.50-0.98).

Conclusion: A reduced oral glucose tolerance was associated with a lower risk of RA. Taken together with the known impact of fat distribution on glucose tolerance, and previous observations of sex-specific effects of BMI on the risk of RA, this suggests that mechanisms related to abdominal or visceral fat may protect against RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reduced-oral-glucose-tolerance-is-associated-with-a-lower-risk-of-rheumatoid-arthritis/