Several semesters ago, I was teaching a course called ‘Human Biology’ as an adjunct. As opposed to my normal class in General Biology, this one contained an anatomy and physiology component. My own history in the lab is one of a molecular and cellular biologist. The only system that I know reasonably well from personal experience is the immune system, so I was learning a lot by teaching this class and doing the reading to remind myself of what I learned many years ago.
I particularly enjoy making class a discussion about specific topics that my students are interested in (even if I cannot always answer such varied questions) and one day a student asked why it was that gastric bypass surgery immediately cured diabetes.
As I said, I’m something of a novice in these areas of systems biology, and given what I knew I could not come up with a reasonable explanation. In fact, I doubted that this could happen and the weekend digging for any publications describing the effect. To my surprise, it was well known. Unfortunately, no one else had a very good explanation for it either. However, as asserted in the associated Perspective article, “gastric bypass surgery patients can stop taking diabetes medications before substantial weight loss has occurred” – a surprising feature of the intervention also seen by my student (who had this surgery himself). This suggests that the surgery itself must trigger a hormonal change in patients, rather that weight loss simply reversing the condition over time.
Happily, the most recent edition of Science caught my eye with an article titled, ‘Reprogramming of Intestinal Glucose Metabolism and Glycemic Control in Rats After Gastric Bypass,’ by Saeidi et al that examined the effect in a rodent model. As Hans-Rudolf Berthoud explains in his review of the work,
“glucose preferably enters the pentose phosphate and other glycolytic pathways that provide substrates for nucleotide and protein synthesis, consistent with accelerated tissue growth. Most important, and as an “unintended” by-product of increased glucose uptake by the expanding gut tissue, systemic glucose concentrations are reduced and the diabetic state is reversed.”
As satisfying as this finding may be, it remains a mystery why this effect would persist long term after the new gut has completed its transformation. An alternate, or perhaps complementary explanation for this effect in humans may lie in the extreme calorie restriction patients are required to adopt post-surgery. “When control subjects were given the same low amounts of food eaten by surgical patients, the same rapid improvements in glycemic control were observed,” providing evidence for a non-surgical pathway to the same endpoint.
One last point…
This article immediately reminded me of work done by Craig Thompson and others on the relationship between obesity, diabetes and cancer, summarized in a review article in a 2009 issue of Science. This article described how it is that obese individuals suffer higher rates of cancer than non-obese persons. Among the links they described was how obesity leads to type 2 diabetes resulting in higher blood sugar concentrations, a condition favorable to oncogenesis.
The same article went on to add that cancer cells often use glucose in a way that that is surprisingly inefficient in terms of the energy it captures (known as the Warburg Effect). This paradox of rapidly dividing cells apparently underutilizing glucose was resolved once it was observed that cancer cells get not only energy from glucose metabolism, but building materials to keep up with the unusually high demand that rapid grown imposes.
Altogether, these articles do much to clarify how the body utilizes fuel, regulates blood glucose and the what the overall health affects of these regulations.