GLASGOW, SCOTLAND — High rates of insulin resistance among patients with rheumatoid arthritis may help explain these patients' increased risk for cardiovascular disease, according to a poster presented by Dr. George D. Kitas at the annual meeting of the British Society for Rheumatology.
Evidence has been increasing that suggests involvement of chronic inflammation in atherosclerosis and coronary heart disease in both rheumatoid arthritis (RA) patients and the general population, but the precise disease processes are not fully understood, Dr. Kitas noted.
Insulin resistance is strongly associated with systemic inflammation. Insulin itself is an anti-inflammatory hormone, the actions of which include suppression of proinflammatory transcription factors and adhesion molecules. It also has antioxidant properties and, in a rat model, suppresses cytokines including interleukin-1β, IL-6, and tumor necrosis factor.
Conversely, hypernutrition and the insulin-resistant state are proinflammatory, noted Dr. Kitas of the department of rheumatology, Dudley Group of Hospitals and the University of Birmingham, both in England.
“Evidence for this arises from observations that treatment of type 2 diabetes reduces C-reactive protein and macrophage chemotactic protein-1,” he wrote. Moreover, diabetic ketoacidosis induces an inflammatory response that normalizes with insulin treatment.
To investigate the prevalence and clinical factors associated with insulin resistance, Dr. Kitas and his colleagues assessed 244 consecutive RA patients. A total of 70.5% were female, mean age was 61.6 years, and mean disease duration was 13.5 years.
Mean body mass index (BMI) was 27.5 kg/m
Rheumatoid factor (RF) was positive in 70.5% of patients. A total of 6.6% already had a diagnosis of diabetes, compared with 2% of the United Kingdom population.
Insulin resistance was determined on the homeostasis model assessment (HOMA) index and the quantitative insulin sensitivity check index (QUICKI).
Among patients who did not have an established diagnosis of diabetes, 37.3% and 38.2% had abnormal findings on HOMA and QUICKI, respectively.
Among these patients with insulin resistance, systolic blood pressure, triglyceride and uric acid levels, and body mass index were significantly higher than in those with normal insulin function. CRP and RF titers also were higher, while high-density lipoprotein level was lower.
Logistic regression analysis found that higher BMI, RF titer, and uric acid level were independent predictors of insulin resistance, according to Dr. Kitas. Steroid use did not correlate with insulin resistance.
The association of elevated RF titer and insulin resistance has not previously been described, he noted. “A possible explanation for this may be that RF acts as a surrogate marker for cumulative inflammation or damage, or it may reflect metabolic or genetic processes influencing insulin sensitivity among RA patients.”
According to Dr. Kitas, the study raises the following questions that require further investigation:
▸ Could improved disease control reduce insulin resistance?
▸ Would BMI reduction and increased exercise reduce insulin resistance?
▸ Do patients with RA and insulin resistance subsequently develop type 2 diabetes?
▸ What is the precise role of RF in insulin resistance?
▸ Will a reduction in insulin resistance ultimately reduce the cardiovascular disease risk in RA patients?