Severe obesity is a chronic condition that, for many people, is difficult to treat with diet or exercise alone, and increases risks for type 2 diabetes, cardiovascular disease, fatty liver disease, and many other devastating health conditions. Bariatric surgical procedures, which restrict stomach size and/or alter the intestinal tract, have been increasingly performed to treat severe obesity when other interventions have not worked. Additionally, bariatric surgery is used in clinical practice for people who have milder levels of obesity along with type 2 diabetes or other serious obesity-related disease. These surgical procedures can have dramatic benefits— such as significant and sustained weight loss, improved control of blood glucose (sugar) levels, or even reversal of type 2 diabetes—especially when accompanied by exercise and a healthy diet. They also carry substantial risks, and researchers have been evaluating the benefits and risks of different procedures.
Despite the increasing popularity of bariatric surgery, crucial questions still remain, such as how best to select candidates for surgery, based on improved definition of specific benefits versus short- and longer-term complications and survival rates, and the effects of different procedures on specific co-morbidities in people with lesser degrees of obesity. While the surgical modifications of the stomach and intestines reduce food intake and the amount of nutrients—including calories—absorbed, emerging evidence is revealing potential additional mechanisms for the effects on weight and metabolism. Researchers would thus like to determine precisely how certain types of bariatric surgical procedures work to help patients lose a considerable amount of weight, maintain weight loss, and improve obesity-related diseases. Finally, there is as yet unexplained heterogeneity in the outcomes of bariatric surgery, ranging from dramatic weight loss and improvement in comorbidities to subsets of patients who fail to lose weight, or who regain weight, and do not have a satisfactory outcome.
Scientists supported by the NIDDK and other organizations have been studying the risks and benefits of bariatric surgery, to help individuals with obesity and their doctors make more informed decisions. Additionally, research on the underlying mechanisms for the effects of bariatric surgical procedures could lead to the development of novel, non-surgical treatments that confer the benefits without the risks of surgery.
Bariatric Surgical Procedures
The first surgery of this type used for severe obesity dates back 50 years and grew out of the results of operations for certain cancers or severe ulcers. Doctors became aware that their patients lost weight following surgeries that removed large portions of the stomach or small intestine. Some physicians began to use such operations to treat patients with severe obesity. Over time, these operations have been modified to improve patient safety and to incorporate technological advances in surgical procedure. There are several general problems involved in assessing the outcomes of bariatric surgery. One is that new surgical approaches and technologies evolve continuously, and are continuing to change at the present time. Secondly, the patient populations who receive bariatric surgery also continue to evolve and may be quite different in individual studies. Together, these issues often make direct comparisons of research studies difficult.
There are several different surgical procedures performed that work through restricting food intake, changing the way in which food is absorbed or metabolized, or both. Physicians performing restrictive operations such as the laparoscopic adjustable gastric banding (LAGB) reduce the opening to the stomach or stomach size. Other procedures such as the biliopancreatic diversion, with or without duodenal switch, restrict the amount of calories and nutrients the body absorbs. The most commonly performed procedure at this time, which has both a restrictive and malabsorptive component, is the Roux-en-Y Gastric Bypass (RYGB). RYGB connects the upper stomach to the lower part of the small intestine, so that food bypasses a large portion of the gastrointestinal tract in which digestion and nutrient absorption normally take place. Increasingly, surgeons are performing a sleeve gastrectomy (SG) procedure in which a portion of the stomach is removed, leaving a sleeve or tube through which food can pass. Over the past several decades, researchers have sought to understand the benefits and risks of different bariatric surgery procedures.
The “Swedish Obese Subjects” Study of Bariatric Surgery
One early large-scale trial was the Swedish Obese Subjects (SOS) study, which remains the largest prospective study on bariatric surgery to date. The landmark SOS study was initiated in 1987. It included more than 2,000 participants who were undergoing bariatric surgery as part of their clinical care, and, as a control group, over 2,000 individuals who had similar health-related measures at the beginning of the study but had declined surgery and instead were receiving usual care. The researchers studied the participants over many years to compare the two groups for overall mortality, weight loss, and other important health outcomes, such as heart attacks, stroke, and type 2 diabetes. When the patients were recruited into the study (from 1987 to 2001), the most common procedure performed was vertical banded gastroplasty, a procedure which is infrequently performed today. RYGB, the most common procedure performed today, was only done in 13 percent of the SOS patients.
The SOS study now has 15 to 20 years of follow-up results. Bariatric surgery was associated with a 29 percent reduction in mortality, which was not correlated with the extent of weight loss. Type 2 diabetes remission after 2 years was 72 percent, and 36 percent after 10 years. Bariatric surgery was also associated with fewer cardiovascular events after more than 10 years. The SOS study found a reduced cancer incidence in women, but not in men, following bariatric surgery. Bariatric surgery lowered medication costs from years 7 to 20, but hospital days and outpatient visits were greater in the surgery group in the first 6 postoperative years. Although the SOS study has yielded important information about the long-term outcomes of bariatric surgery, most patients in the study underwent procedures that are no longer performed today.
The Longitudinal Assessment of Bariatric Surgery (LABS) Study
Many other bariatric surgery studies have been performed over the past few decades. However, the generalizability of some of these studies has been limited by a variety of factors, such as relatively small numbers of participants, lack of diversity in geographic locations or populations, non-standardized research practices, and short-term follow-up. Thus, in 2003, the NIDDK began a new research effort in bariatric surgery. The Institute partnered with researchers at multiple sites across the country to create the Longitudinal Assessment of Bariatric Surgery (LABS) consortium. The goal was to facilitate and accelerate clinical, epidemiological, and behavioral research to address key long-term outcomes of bariatric surgery, with a planned follow-up of at least 5 years. Between 2004 and 2009, the multi-center LABS consortium enrolled thousands of patients with severe obesity who were already planning to undergo bariatric surgery. The geographically diverse participants were evaluated at baseline and annually with standardized measures by trained personnel to address important questions about the comparative efficacy and safety of surgical procedures, as well as the durability of weight loss and health improvements. The overall goal of this observational research was to provide evidence that can be broadly applicable to clinical practice.
LABS has already provided critical insights into the risks and outcomes of bariatric surgical procedures. One early report followed 4,776 patients with severe obesity who had bariatric surgery, from before their surgery through the first 30 days following surgery, to evaluate death and complication rates. The study took place over 2 years at 10 U.S. medical centers, with one center coordinating data collection and analysis. Within 30 days of surgery, 4 percent of patients had at least one major adverse outcome, defined as development of blood clots in the deep veins of the legs or the pulmonary artery of the lungs, repeat surgeries, not being discharged from the hospital within 30 days, or death. Mortality rates were low: fewer than 1 percent of patients died within 30 days. This evaluation highlights the level of short-term risks associated with bariatric surgery.
An important goal of the LABS consortium is to determine longer-term outcomes of bariatric surgery. One study, reported in 2013, found that adults with severe obesity had substantial weight loss 3 years after bariatric surgery (RYGB or LAGB) with significant improvements in diabetes, high blood pressure, and cholesterol outcomes, although results varied among the study participants. A majority of the study participants lost the most weight during the first year. Overall, the median weight loss after 3 years for individuals who underwent RYGB was 31.5 percent of the body weight they had before surgery, compared with 15.9 percent weight loss for those who had LAGB surgery. Many participants had at least partial remission of type 2 diabetes, improvements in high blood pressure, and a reduction in excess fats in the blood. Although both procedures were effective, RYGB consistently led to greater health improvements than LAGB. For both procedures, fewer than 1 percent of study participants died within 3 years. Only 0.3 percent of patients who had RYGB required subsequent bariatric surgery, whereas 17.5 percent of individuals who received LAGB needed additional surgery, such as band replacement, band removal, or revision to another bariatric surgical procedure. Thus, RYGB, and to a lesser degree LAGB, leads to significant weight loss and reduction in obesity-related health conditions after 3 years, but the extent of these improvements is variable.
LABS investigators are also seeking to understand behavioral predictors and outcomes of bariatric surgery. For example, researchers found that adults who had RYGB were at significantly higher risk for alcohol use disorders (AUD) 2 years after surgery compared with before surgery. Among participants who had the RYGB procedure, there was no significant increase in AUD 1 year after surgery. By the second postoperative year, however, there was a relative increase in AUD of more than 50 percent in participants who had RYGB compared to pre-surgical rates. Patients who underwent gastric banding did not report an increase in AUD symptoms. While a number of predictors for AUD were identified, these results suggest that clinicians should be aware of the importance of monitoring for signs and symptoms of AUD and consider counseling after bariatric surgery, particularly in patients who undergo RYGB.
In addition to funding research on outcomes in adults, the NIDDK also supports the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Although not common in adolescents, the use of bariatric surgery in this age group has been increasing in clinical practice. Thus, the Teen-LABS study was launched in 2007 to assess the short- and long-term risks and benefits of bariatric surgery among teens with severe obesity. This observational study enrolled 242 teens who were already planning to have bariatric surgery. The participants underwent either RYGB, SG, or gastric banding, and they were evaluated for major, life-threatening complications (e.g., bowel obstruction/bleeding, gastrointestinal leaking, deep vein thrombosis, and splenectomy), as well as for minor, non-life-threatening, complications (e.g., pneumonia, urinary tract infections or other complications, bowel injury, and hypertension). At 30 days after surgery, there were no deaths; 8 percent of the participants experienced major complications; and 15 percent experienced minor complications. Thus, over the short-term, bariatric surgery led to relatively few complications. Teen-LABS investigators will continue to study the participants to determine longer-term safety, health, and weight outcomes of bariatric surgery in teens.
Mining Health Databases to Evaluate Outcomes of Bariatric Surgery
In another type of effort to gain insights on bariatric surgery outcomes from relatively large numbers of patients, researchers have sought to use data from pre-existing databases to perform retrospective analyses. For example, one group of scientists, supported by the Agency for Healthcare Research and Quality, examined data from the electronic medical records of 1,395 adults with severe obesity and with type 2 diabetes, from 20 centers across the United States, who had bariatric surgery—most had RYGB, but a small percentage had other procedures—and more than 62,000 who did not. The goal of this study was, at 2 years after surgery, to compare various health outcomes, including diabetes remission and death. The researchers’ analyses, published in 2012, showed that in this large, multi-center study, the patients who had bariatric surgery achieved higher rates of diabetes remission, with no increased risk of death, compared with patients who received usual care.
Scientists in another study, supported by the NIDDK, also used electronic medical records of 690 patients who had RYGB surgery to develop an algorithm, called the DiaRem score, that can predict the likelihood of postoperative type 2 diabetes remission. Sixty-three percent of the patients achieved partial or complete diabetes remission after the surgery. The researchers examined 259 different pre-operative clinical variables, and found that four standard measures could effectively predict type 2 diabetes remission: insulin use, age, circulating glucose levels, and type of anti-diabetes drugs. This predictive model could provide a tool for clinicians and patients to help consider whether bariatric surgery might be an appropriate treatment option, and to better manage type 2 diabetes after the operation.
Clinical Trials of Bariatric Surgery for Obesity and Type 2 Diabetes
While observational and retrospective studies can provide insights about risks and benefits of bariatric surgery, proving its health impact would require long-term randomized, controlled trials (RCTs), which are difficult and costly to undertake. In the past few years, several relatively small RCTs enrolled participants with type 2 diabetes who either underwent bariatric surgery or were given one of a variety of non-surgical treatments for obesity and/or diabetes. After short-term follow-up, bariatric surgery procedures resulted in greater weight loss and greater remission of type 2 diabetes compared with the non-surgical options.
In addition to research focusing on people with severe obesity, recent clinical trials have been conducted to gain preliminary insights into the risks and benefits of bariatric surgery for type 2 diabetes in people with milder levels of obesity, as defined by body mass index (or “BMI,” a measure of weight relative to height). For example, reports of two small, NIDDK-supported short-term trials published in 2014 found that bariatric surgery may be more effective than non-surgical approaches for treating type 2 diabetes in adults who have moderate (BMI 35 to 40) or mild (BMI 30 to 35) levels of obesity. In one trial, 69 volunteers with type 2 diabetes were randomly assigned to receive either bariatric surgery or an intensive lifestyle intervention for weight loss, and health outcomes were compared after 1 year. About one-half of the individuals who underwent RYGB and 27 percent of those who underwent LAGB had partial diabetes remission. Their blood glucose levels were no longer in the diabetes range, and they were able to discontinue their diabetes medications. None of the people in the lifestyle intervention group had partial or complete diabetes remission. However, several individuals in the RYGB and LAGB groups experienced complications, including a surgery-related ulcer and dehydration. In another trial, investigators assigned 43 volunteers to receive either RYGB surgery or a lifestyle and medical intervention of diet and exercise, delivered in group sessions, with a weekly medication adjustment plan. After 1 year, 58 percent of the individuals in the RYGB group, but only 16 percent of those in the lifestyle and medical therapy group, saw their blood glucose levels improve to the target for glucose control chosen as the study outcome. Weight loss was greater in the RYGB group as well. Importantly, while assessing the safety of the interventions, the researchers noted several adverse events among participants in the RYGB surgery group, including ischemic heart disease requiring coronary artery bypass surgery and depression with attempted suicide. In the non-surgical group, a few individuals experienced near-fainting.
The results of these studies were similar to other RCTs, which found improved weight and diabetes outcomes for the bariatric surgical groups when compared to those receiving non-surgical treatments for obesity or diabetes. However, RCTs are difficult to perform, generally small, and of short duration. Given these challenges, high-quality, carefully designed observational studies might be preferable to answer questions about the safety of bariatric surgery, as well as the durability of weight loss and health improvements.
While a picture may be emerging regarding the safety and efficacy of bariatric surgery as a treatment for obesity in the short- and medium-term, further research is needed to better understand the long-term risks and durability of positive outcomes. Additional avenues of clinical research, such as efforts to elucidate the behavioral and psychological factors that influence the trajectory of weight loss after bariatric surgery, could also inform clinical decisions for the treatment of obesity and its complications.
Researchers are also investigating the molecular mechanisms behind physiological changes that occur following bariatric surgery. Emerging evidence suggests that the beneficial effects of bariatric surgery may extend beyond the physical restrictions of the surgery, malabsorption, and the postoperative reduction of calorie intake. For example, scientists have observed near immediate improvements in type 2 diabetes and other metabolic complications prior to weight loss following bariatric surgery, but the reasons for the dramatic change in glycemic control are not yet well understood. Other physiological effects, such as alterations in the types of bacteria that normally reside in the gut (the gut microbiome) and changes in hormones, metabolic factors such as bile acids, and nervous system pathways controlling feeding behavior and metabolism are also under investigation. These and other studies may ultimately provide the foundation for non-surgical therapies, including medications and devices, to achieve health improvements similar to those following bariatric surgery, but perhaps without the associated risks.