UBC Reports | Vol. 53 | No. 1 | Jan. 4, 2007
Finding the Treatment, and Possibly Cure, for Diabetes in the Human Gut
By Timothy Kieffer
Assoc. Professor of Cellular and Physiological Sciences
Diabetes threatens to become a global health crisis. Many predict that unless we begin altering the behaviours that put our young people at risk of developing the disease, treating diabetes and its complications is going to dominate future health care expenditures. Indeed it is predicted that one of three children born now will develop diabetes. Approximately 250 million already have the disease and it will present them with debilitating complications like blindness, kidney failure and limb amputations. Even with treatment, diabetes currently reduces life span by an average of 15 years; about three-quarters of patients die of stroke or heart attack.
More than two-thirds of people with diabetes are obese. They require drugs that stimulate beta-cells to make more insulin and/or drugs that help insulin work better. When these don’t work any longer, people require insulin. Unfortunately this form of diabetes is growing at an alarming rate, along with our waistlines. There are already approximately one billion obese individuals, with the incidence tragically growing most in our children. Fat-laden and sugar-rich food combined with lack of physical activity appear to be the sinister recipe.
The good news?
There are exciting new therapies on the way that have the potential to not only treat diabetes, but perhaps even cure it. The US Federal Drug Administration recently approved new therapies that harness GLP-1 and the UBC-discovered hormone GIP, a class of gut hormones called incretins, that are released from the gut during meals and stimulate insulin release. Unlike currently used drugs, these incretins also entice the pancreas to manufacture more insulin and even to make more beta-cells. Thus, when combined with an immunosuppressor, these agents may actually coax the body to help itself, even in those with long-standing type 1 diabetes. They may also be good for the heart. The first incretin-based therapy, ByettaTM, is now available in the US. As an added reward, many taking ByettaTM lose a substantial amount of weight.
UBC researchers discovered another way to take advantage of incretins. They noted that the body produces an enzyme, DPP4, that normally destroys incretins. They went on to show that inhibitors of DPP4 could enhance incretin levels and thereby improve control of blood sugar levels. The first DPP4 inhibitor, JanuviaTM, will be on the market soon, and others will follow.
Scientists on campus are also developing ways to coax the gut incretin cells into making insulin. The natural ability of these cells to release hormones at meal-time means that this strategy could eliminate the needle injections and guess work associated with traditional insulin therapy. The same strategy might be used to boost the release of satiety factors – agents that make us feel full. Feeling full sooner could help curb overindulgence.
Additional remedies will likely come from the gut. Gastric bypass -- a surgical procedure that results in food bypassing a portion of the stomach and intestine -- results in profound weight loss by limiting the amount of food the patient can comfortably eat. Remarkably, it can also cure diabetes before pounds are shed; it is not simply a matter of eating less. Within the next few years we will likely learn how gastric bypass reverses diabetes such that we can replace the scalpel with pills that produce the same effects.
Researchers are working feverishly in both academic and industrial settings to arrest the epidemic of both obesity and diabetes. They say the way to a man’s heart is through his stomach...in this case it just might be true.
What Exactly is Diabetes?
Simply put, it is diagnosed by excessively elevated levels of blood sugar. It results from a deficiency of insulin -- a hormone produced from specialized cells of the pancreas, called beta-cells. Insulin moves the sugar we consume out of the blood and into cells to be used for energy. When there is insufficient insulin, cells starve, and if not caught soon enough, death results.
What Causes Diabetes?
Unfortunately we still don’t know, but we have a general idea. In type 1, an over-zealous immune system destroys the insulin making beta-cells. This means life-long insulin replacement, typically by needle with every meal at a dose estimated to match the sugar content of the food. Multiple daily blood sugar measurements are required to monitor effectiveness. Imagine a parent trying to explain that to a newly diagnosed child.
A more prevalent form of diabetes, type 2, is associated with obesity. Added fat requires more insulin, a task the beta-cells are usually up for. However, for some, beta-cells eventually falter and blood sugar levels start to rise.