Bariatric surgery continues to provide impressive outcomes. But how surgery achieves these outcomes is still unclear. What is known is providing new avenues for research.
A recent review of 14 studies involving 29,000 bariatric surgery patients and 166,200 nonsurgical controls of bias a more than 50% reduction in mortality amongst patients who had bariatric surgery. Bariatric surgery was associated with a significantly reduced risk of composite cardiovascular adverse events and was also associated with significant reduction in specific endpoints of myocardial infarction and stroke. And a study by Philip Schauer and colleagues published in the New England Journal of Medicine found, after 3 years of follow-up, that patients who received bariatric surgery and intensive medical therapy had better glycemic control than patients who received only intensive medical therapy. All patients had uncontrolled type 2 diabetes. 38% of surgical plus medical patients achieved the primary end point of HbA1c levels of 6% or less compared to 5% in the medical-only group. Weight loss differences were stark. The group receiving gastric bypass surgery had a 24.5% reduction in baseline weight and the group receiving sleeve-gastrectomy has a 21% reduction. Those in the medical-only group had a weight loss of 4.2%. The surgery plus medical group had greater reductions in medications and improved quality of life scores than the medical only group.
Earlier studies by Walter Poires at East Carolina University showed that, 16 years after Roux-en-Y gastric bypass (RYGB), patients mean weight loss was 55% of excess body weight, about 106 pounds. Mortality rates 9 years after surgery were 1% a year compared to 4.5% per year in the control group. Obesity-related comorbidities, including type 2 diabetes, hypertension, sleep apnea, non-alcoholic steatohepatitis, stress incontinence and asthma, were resolved.
How bariatric surgery resolves type 2 diabetes in over 80% of patients still remains to be determined. Theories abound. It has been observed that bariatric surgery blunts adaptive thermogenesis which takes place with other weight loss interventions, resulting in greater, more durable weight loss. Changes in gut hormones may also play a key role. A recent paper found that changes in bile acids in the blood. In a mouse study, the FXR gene influenced the outcomes in sleeve gasterctomy while mice without the gene had no effects. Researchers believe that it is bile acids in the blood, not the reduction in size of the stomach that produce the weight loss effects.
RYBG appears to work by reducing food intake and increasing resting energy expenditure. Taste, smell and appetite change after RYGB. A recently published survey of 103 RYGB patients reported high rates of changes in appetite, taste and smell up to 3 years after surgery. 73% of patients developed aversions to specific foods with meat, sweets, dairy and junk/fried foods leading the aversion list.
Changes in absorption of foods in the duodenum have triggered research and the development of a novel medical device, the EndoBarrier, being developed by GI Dynamics Inc. and presently in use in Europe, South America, Australia and Israel. Researchers are also looking at drugs which may mimic the effects of surgery, including a ‘cocktail’ of GLP-1, neuropeptide PYY, and oxyntomodulin, perhaps in combination with leptin to avoid the adaptive thermogenesis effect.
What has become evident is that earlier thinking on bariatric surgery, that operations are either restrictive or create malabsorption of nutrients, is inadequate to explain the power of the outcomes. Therefore, scientific focus has shifted to understanding the physiological changes brought about by bariatric surgery. This, in turn, is fueling the drive to find ways to achieve the effects of bariatric surgery without the surgery. As surgery is limited by costs, skills of surgeons, availability of facilities, etc., a non-surgical approach using the new understanding of the mechanisms has the potential to create new therapies.
There are two excellent podcasts on the mechanisms of bariatric surgery from the University of Alabama, Birmingham, NORC. See Lee Kaplan, Ph.D. M.D. and Randy Seeley, Ph.D.