Elevations in Adipocytokines and Mortality in Rheumatoid Arthritis

Joshua Baker, MD, from the Perelman School of Medicine at the University of Pennsylvania, has conducted several studies into the possible associations of body composition, body mass index, and obesity with the risk of developing rheumatoid arthritis. Recently Dr Baker and colleagues from around the United States looked at another yet factor: elevations in adiponectin and leptin and their possible association with RA.

Dr Baker agreed to answer a few questions we had about this research.

RALN: First, can you give us an overview of adiponectin and leptin—what are they, what are their functions, and how can high or low levels affect health?

Dr Baker: Adiponectin and leptin are both rather abundant proteins in the blood that are thought to help regulate how we use energy. They control things like appetite, metabolic rate, and how the body uses fat stores for making energy. Because of their association with energy and appetite, they are strongly associated with body fat. People who have a genetic reason why they don’t make leptin tend to be obese, presumably because their appetite cannot be suppressed and because they are unable to correctly process energy.

RALN: What led you to think that adiponectin and leptin might be associated with RA?

Dr Baker: I have been interested in how inflammation can affect energy usage in the body. Active inflammation can use up a lot of energy and is likely to disrupt the way that the body makes and stores energy. Therefore, I hypothesized that changes in the levels of adiponectin and leptin might help to identify people who have had disturbances in the way that they use energy, and that these people would be at the greatest risk of bad health outcomes. 

RALN: Would you give us a brief overview of your study?

Dr Baker: We studied approximately 2583 patients from the Veterans Affairs rheumatoid arthritis registry and determined whether levels of adiponectin and leptin at enrollment in the study were associated with earlier mortality. We also looked at how these molecules were associated with measures of systemic inflammation in the blood.

RALN: In the abstract of your article, you noted that this study “assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with rheumatoid arthritis (RA).” What did you find out?

Dr Baker: We observed that those with high adiponectin and high leptin levels were at significantly higher risk of early death. Those patients who had a high leptin and a high adiponectin level had a 73% higher risk of death. We also saw that those with the highest adiponectin levels had higher levels of inflammation.

RALN: What conclusions have you drawn from the results of this study about whether—and how—adiponectin and leptin may affect or be associated with RA and mortality?

Dr Baker: This study suggests that adiponectin and leptin may help identify those patients at higher long-term risks of death. Whether the association is causal is not possible to determine from our study.

RALN: How do you think this information might be applied in clinical practice? Could this association, for example, drive development of new therapies or new protocols for treatment of RA?

Dr Baker: It’s too early to know whether measuring these molecules in clinical practice could aid in formal risk prediction for clinicians who are making clinical decisions. However, a long-term goal for RA would be to find tools to help identify patients at high risk, for whom early and aggressive therapy is most important.

RALN:  What other research needs to be done on this topic? Are you planning any additional studies?

Dr Baker: We have planned or published several other studies evaluating how these molecules predict other outcomes important in patients with RA, such as improvements in disease activity, cardiovascular events, and fractures. We still need better mechanistic studies to understand whether adiponectin and leptin have direct effects on inflammation and contribute themselves to worse health outcomes.

Reference:
Baker JF, England BR, George MD, et al. Elevations in adipocytokines and mortality in rheumatoid arthritis. Rheumatology; 2022; keac191. DOI:10.1093/rheumatology/keac191