Metabolic Syndrome Linked to Higher Risk for Immunological Disorders

Patients with RA and diabetes may benefit for both conditions from a TNF antagonist.

The metabolic risk factors that together earn the title metabolic syndrome turn out to not only raise the risk for metabolic disorders, such as diabetes, but also increase the risk for traditional immunological disorders, such as rheumatoid arthritis (RA), gout, psoriasis and Crohn’s disease. These conditions all appear to be driven by inflammatory processes that are also associated with diabetes. Moreover, some of these immunological diseases appear to be at the end of molecular pathways that also lead to metabolic disorders. All of this prompts the question: Is it time to start treating diabetes with the same types of drugs that we use to treat immunological disorders?

Multiple antiinflammatory drugs are under development or are already approved for the treatment of many diabetes-associated immunological conditions. Is it possible to repurpose these drugs for the treatment of diabetes itself? Alternatively, if diabetes is reconceived as an inflammatory disease, will new drug targets be revealed?

Marc Y. Donath, MD, of University Hospital in Basel, Switzerland, believes so. He recently published a review article describing potential treatment strategies that target inflammation in patients with type 2 diabetes.¹ In his article, he describes the rationale for an immunomodulatory approach to the treatment of type 2 diabetes. He also surveys the single molecule targets that have thus far been identified for drug discovery and describes what could be expected when they are prescribed to patients with diabetes. He goes on to paint a picture of a future with drugs that act on an underlying dysfunctional pathway, normalizing the immune response and improving a patient’s health without specifically targeting a disease.

Dr. Donath’s approach is not only academic, but also clinical. “Antiinflammatory drugs are not approved yet for the treatment of diabetes alone. However, if I have a reason to treat a patient for a concomitant condition with such a drug, as described above [RA and gout], I am already doing it with sometimes impressive improvement of both conditions,” wrote Dr. Donath in an e-mail to The Rheumatologist.

Dr. Donath is also contributing to the creation of this next wave of diabetes drugs. He is listed as the inventor on a patent (WO6709) filed in 2003 for the use of an interleukin 1 (IL-1) receptor antagonist for the treatment of, or prophylaxis against, type 2 diabetes.

Target Molecules

Most investigators agree that inflammation plays a role in the pathogenesis of type 2 diabetes. Numerous studies have demonstrated that increased inflammation is associated with increased insulin resistance. Moreover, several inflammatory targets have been identified that may affect metabolism. These targets include tumor necrosis factor (TNF) and IL-1β. Twenty years ago, investigators discovered that TNF plays a role in insulin resistance in rodents. The work in rodents was followed by a human clinical trial that demonstrated that sustained TNF inhibition in obese individuals without diabetes resulted in a statistically significant decrease in fasting glucose and an increase in adiponectin.