Mechanisms of improved glucose handling after metabolic surgery: The Big Six

摘要

For some time, it has been clear that elevated glucose is detrimental to the organism. A plethora of medicines have been introduced to reduce the fasting and postprandial glucose levels (including insulin, GLP-1 agonists, and SGLT2 inhibitors, among others). While these medications are useful to reduce tissue exposure to glucose, no single compound and no combination have been able to totally normalize the blood sugar. Thus, it was astonishing when it was reported that surgery of the gastrointestinal tract could not only reduce obesity but also normalize the blood sugar. These discoveries have transformed diabetes research. What is it about bariatric surgery that causes the remarkable amelioration of glucose homeostasis dysregulation? The answer to this million dollar question is a billion dollar answer. However, a new perspective could shed some light and help provide a clear path for investigation. Instead of asking what does bariatric surgery do to change the pathophysiology, we can be asking what pathophysiology and risk factors confer a greater success with remission and improved disease state following surgery. Work from our lab and others can help to offer a physiological basis for what mechanisms may be put into play when the anatomy is altered during surgery. Here, we do not offer an explanation of the mechanism of action of bariatric surgery, but rather provide a background on the regulation of blood glucose and how it is altered during both the diseased state and, as available, the remission state.