Obesity, Inflammation, and Diabetes

Diabetes is, in the most basic sense, an inability to properly regulate blood glucose levels. The consequences of having chronically high blood glucose can be severe – ranging from circulatory problems to glaucoma, blindness, coma, and death. The diabetic population has rapidly increased over the past few decades, largely due to an increase in the number of Type 2 diabetics. Type 2 diabetes is also known as non-insulin dependent diabetes – their tissues are no longer sensitive to insulin’s cues to absorb blood glucose. Type 1 diabetes is an autoimmune disorder in which the patient’s own immune system destroys the insulin-producing pancreatic beta cells, with symptoms typically appearing in childhood or adolescence. Type 2 diabetes, in contrast, most often occurs in individuals over forty. The exact causes of type 2 diabetes is not known, but it is now well-established within the medical community that obesity significantly increases one’s risk for Type 2 diabetes. But what exactly is the connection?

Various key research studies over the past several years have pointed to one factor: inflammation. In susceptible individuals, the presence of excess fat deposits – obesity – triggers an infiltration of the immune responder cells known as macrophages. In a healthy person, macrophages play a critical role in defending against foreign invaders such as a cold virus. They work by recognizing the foreign invader – for example, a virus-infected cell – and engulfing it, resulting in the pathogen’s destruction. Macrophages also release chemical signals known as cytokines, which serve to activate other immune cells, which in turn release additional cytokines. This sort of immune response is known as the inflammatory response – and under normal circumstances, is a highly efficient and effective mechanism for ridding the body of foreign pathogens, and which dissipates once those pathogens are cleared. However, if this inflammatory response is initiated by fat deposits within an individual’s body, it will not dissipate as long as those fat deposits remain – setting the stage for chronic inflammation.

Why is chronic inflammation problematic? Think back to the last time that you had the flu, or scraped or bumped your knee. In the case of the flu, you probably felt pretty miserable for a week or so, and most likely experienced a fever. A scraped or bumped knee may result in swelling and heat at the site of injury. These symptoms are actually the result of cytokine production and subsequent inflammatory response – necessary to aid in healing, but damaging and uncomfortable if chronic. In the case of diabetes, it is thought that chronic inflammation plays a role in insulin resistance by interfering with insulin’s signaling mechanisms and by damaging the pancreatic beta cells that produce insulin. Some studies also suggest that chronic inflammation may interfere with the actions of the hormone leptin – a key factor in appetite control, thus interfering with the ability to lose excess fat, setting up a vicious cycle.

Several unanswered questions remain, however. Not all obese individuals suffer from chronic inflammation and diabetes. This suggests that there are genetic factors at work as well – some people are predisposed to having an inflammatory response to the systemic stress caused by excess fat. A related observation is that not all type 2 diabetics are obese or even overweight – about twenty percent are normal weight individuals. These normal weight individuals, however, most often also exhibit chronic inflammation.

Current diabetes treatments focus on insulin support therapy for type 1 diabetics, and attempts at increasing insulin sensitivity or modulating the rate at which glucose enters the blood for those with type 2. The next generation of type 2 diabetes will likely target inflammatory pathways. Physicians have known for some time that patients with rheumatoid arthritis (RA) – an inflammatory disease in which the patient’s immune system attacks the body’s flexible joints, resulting in pain, swelling, and restricted movement – were more likely to get type 2 diabetes. A recently published study in the Journal of the American Medical Association reports that RA patients being treated with inhibitors of inflammatory cytokines such as Enbrel, Humira, and Remicade had lower diabetes risk than those using other means to control the disease. Clinical trials are currently underway to directly test the efficacy of Anakira, another ant-inflammatory RA drug, in diabetes management.

Combined with diet and exercise, these new anti-inflammatory
approaches to diabetes management may provide better health to millions of sufferers.