Considering the Possibility of a Type 4 Age-Related Diabetes
Type 1 diabetes is an autoimmune disease, type 2 diabetes is a lifestyle disease largely caused by being overweight, some researchers have suggested that Alzheimer's disease is a type 3 diabetes, and here evidence is presented for the existence of a type 4 age-related diabetes:
Diabetes is often the result of obesity and poor diet choices, but for some older adults the disease might simply be a consequence of aging. New research has discovered that diabetes - or insulin resistance - in aged, lean mice has a different cellular cause than the diabetes that results from weight gain (type 2). And the findings point toward a possible cure for what the scientists are now calling a new kind of diabetes (type 4). "A lot of diabetes in the elderly goes undiagnosed because they don't have the classical risk factors for type 2 diabetes, such as obesity. We hope our discovery not only leads to therapeutics, but to an increased recognition of type 4 diabetes as a distinct disease."
Researchers set out to compare the immune systems of healthy mice, those with obesity-related diabetes and those with age-related diabetes. The mice with age-related disease, they found, had abnormally high levels of immune cells called T regulatory cells (Tregs) inside their fat tissue. Mice with obesity-related diabetes, on the other hand, had normal levels of Tregs within the tissue, despite having more fat tissue. Normally, Tregs help calm inflammation. Because fat tissue is constantly broken down and built back up as it stores and releases energy, it requires low levels of inflammation to constantly remodel itself. But as someone ages, the new research suggests, Tregs gradually accumulate within fat. And if the cells reach a tipping point where they completely block inflammation in fat tissue, they can cause fat deposits to build up inside unseen areas of the body, including the liver, leading to insulin resistance. "It was a little bit surprising since normally Tregs are supposed to be beneficial for the body."
When the scientists blocked Treg cells from accumulating in the fat by targeting a molecule that the immune cells require, mice no longer developed type 4 diabetes in old age. However, if mice became obese, blocking the Tregs in fat did not prevent type 2 insulin resistance. "It turns out that for this type of diabetes, the treatment is not losing weight. The treatment is actually losing these cells, and we show that it's possible to do that." The researchers now want to find out exactly how Tregs interact with fat tissue and whether the immune cells accumulate in other organs during normal aging. They're also planning studies to see whether the results hold true in humans. "We're working with clinicians to get samples from older, lean people with diabetes to see if this cell type is also implicated in human disease."