Can We Surgically Treat Diabetes?

We live in a country where fast food is cheaper than eating healthy and where a McDonald’s is always just around the corner. Obesity and diabetes have become all too common in America. In fact, the number of Americans afflicted by obesity and diabetes has reached epidemic proportions.

             

While the preferred treatments for obesity and diabetes include dieting, exercise and pharmacotherapy, doctors have recently started to consider surgical intervention for more severe cases.

             

While undergoing extremely invasive surgeries such as intestinal bypass (where the duodenum and jejunum are bypassed thereby shortening the length food travels in the small intestines as a means to reduce the absorption of nutrients) and gastric resection (where food intake is mechanically reduced by restricting the volume of the stomach) may seem unpleasant, they have started to become the preferred and more popular surgeries to help afflicted patients lose weight. However, these surgeries have more complex effects than simply causing you to lose weight; for example, one beneficial side-effect to such surgeries have been the remission of type 2 diabetes post-operation. If not to treat obesity and diabetes, studying these two procedures may allow us to better understand the physiological and homeostatic roles our stomach and small intestines play. 

Sarruf DA, Bonner-Weir S, Schwartz MW. New clues to bariatric surgery’s benefits. Nature Medicine. 18: 860-861 (2012).

From Barnes Bariatric in Dallas/Fort Worth, Texas (http://barnesweightlosssurgery.com/gastric-sleeve-surgery/)

In order to test the homeostatic roles of the small intestines and the stomach in regards to sugar metabolism, Rajesh Patel and a group of researchers at Weill Cornell Medical College in New York City tested the two surgical procedures (gastric resection and intestinal bypass) in diabetic, fatty rats. They operated on the rats giving them either a gastric resection or an intestinal bypass and then looked at changes in their food intake, body weight, glucose tolerance and levels of various hormones. 

The researchers found that gastric resection surgeries showed significantly reduced food intake, which makes sense because their stomachs are smaller. This decline in food intake, in turn, resulted in a significant decrease in body weight, which again makes sense. However,  food intake in the long run was no different than the control rats suggesting that maintaining a healthy weight requires more than just surgery, it also requires a desire to keep that weight off through continuous discipline and health-oriented actions post-operation. On the other hand, for rats that underwent intestinal bypass, they had only a transient decline in food intake for the first week post-operation, which I believe may be the result of post-operation discomfort and distress. Regardless, intestinal bypass resulted in no significant change in the rats’ body weights.

           

But there is a silver lining for the rats that underwent the intestinal bypass according to Rajesh Patel’s research lab. The researchers found that rats that underwent intestinal bypass did show a significantly higher oral glucose tolerance than either the control or those rats that underwent the gastric resection surgeries. So while these rats don’t look any skinnier, they can rest easy knowing they can eat more sweets! All jokes aside, this is very strange to see that elimination of a portion of your intestines results in being able to better manage glucose homeostasis. While trying to discern the reasoning for this phenomenon, the researchers looked towards hormones, the regulators of many homeostatic functions in our body.

             

When looking at the hormones, they looked at insulin and glucagon among other hormones. They found that the increased glucose tolerance in rats that underwent intestinal bypass was insulin-independent because no significant change was found in the levels of insulin relative to the controls. But strangely, they also found that intestinal bypass restored glucagon suppression comparable to healthy rats. While the mechanism for such a process is still uncertain, we now have evidence that suggests our small intestines may have a more complex function than we initially believed. It’s crazy to think that we still aren’t aware of just how complex our body’s homeostatic control is.

             

It’s true that we see increased glucose tolerance in rats with the intestinal bypass, but that could be a result of other variables. The gut microbiota may have changed causing altered glucose absorption, bile acid perturbation as a result of the bypass (and bile acids have been shown to prevent insulin resistance), and potential changes in neuroendocrine signaling could all account for the changes observed. But pinpointing exactly what the cause is will require further studies.

            

Ultimately, we hope that studying these invasive surgical interventions in rats not only help us to improve the lives of afflicted human patients, but also inform us about our own bodies to allow more potent pharmacotherapeutic alternatives to deal with our current epidemic.

References:

Patel RT, Shukla AP, Ahn SM, Moreira M, Rubino F. Surgical control of obesity and diabetes: the role of intestinal vs. gastric mechanisms in the regulation of body weight and glucose homeostasis. Obesity Biology and Integrated Physiology, 22:(1) 159-169 (2014).