ARRA IMPACT REPORT:
Bariatric Surgery – Effects on Obesity and Type 2 Diabetes


Public Health Burden
Over 35 percent of adults and nearly 17 percent of children and teens in the United States are obese,1 and obesity is a major contributor to type 2 diabetes and many other diseases. Because prevention and treatment of obesity through lifestyle intervention and medication remain challenging, the use of bariatric surgical procedures has increased substantially in recent years as a treatment for people with extreme obesity (defined as a body mass index, BMI, of 40 kg/m2 or greater) and for those who have moderate levels of obesity (a BMI between 30 and 40) accompanied by type 2 diabetes or other serious conditions—despite limited data on risks and benefits.

Basic Research to Understand How Bariatric Surgery Affects Obesity and Type 2 Diabetes
Bariatric surgical procedures modify the digestive tract to limit food intake, decrease nutrient absorption, or both, and can lead to substantial weight loss for obese people. There have also been reports that bariatric surgical procedures can improve blood glucose levels and lead to remission of type 2 diabetes, even before substantial weight loss occurs. Bariatric surgery results in changes in signaling molecules, such as hormones produced in the digestive tract, which may contribute to weight loss and diabetes improvements, but the mechanisms are not yet clear. ARRA-funded studies to gain deeper understanding of these biologic mechanisms, using animal models, are helping to inform the use of surgery and may spur development of new treatment approaches.

  • Effect of Obesity-associated Gene Variants on Weight Loss after Bariatric Surgery: In research in mice, scientists sought to determine whether weight loss after bariatric surgery is affected by obesity-associated variants in a gene called MC4R.2 Mice and people have two copies of this gene; variants in one copy can cause obesity, even if the other copy is normal. With ARRA funding for both a small animal surgery resource and for a center specializing in metabolic analyses in mice, the researchers showed that MC4R gene function is important to achieve sustained weight loss after bariatric surgery, and that one normal MC4R gene is sufficient for this effect. In related research, these investigators observed that people with one variant and one normal MC4R gene lose as much weight after bariatric surgery as those with two normal MC4R genes. Together, these results provide clues to the mechanism of action of bariatric surgery that can help inform treatment, and it also demonstrates the value of the ARRA-funded small animal research which provided insights into how bariatric surgery works in humans.
  • Delaying the Onset of Type 2 Diabetes: Recognizing that bariatric surgery can reverse type 2 diabetes, another ARRA-funded team of scientists investigated the potential for the prevention or delay of diabetes. Using a rat model, and focusing on a bariatric surgical procedure called vertical sleeve gastrectomy (VGS), the researchers discovered that this procedure can delay diabetes onset and also improve blood lipid levels, likely as a result of modulating levels of biological signaling molecules.3 They also found that VSG surgery has its effects in part through mechanisms that are independent of weight loss: 1) it boosts levels of biological molecules known to reduce appetite or have other metabolic benefits; 2)reduces levels of an appetite-promoting hormone (ghrelin); and 3) improves insulin levels. Although further research is needed to assess effects in humans, this study suggests that VSG surgery can delay type 2 diabetes onset and may lead to new pharmaceutical approaches that target the biological molecules involved.

Advancing Clinical Research Efforts
Although bariatric surgery has increasingly been used in obese adults and adolescents for weight loss and for its reported effects on type 2 diabetes, there has not been substantial data on safety and efficacy, including longer term effects. Important areas of NIH-funded clinical research thus include:

  • determining the effects of bariatric surgical procedures on the health of individuals with extreme obesity and with lesser obesity accompanied by type 2 diabetes and other obesity-associated medical conditions; and
  • understanding how these surgical procedures compare to each other and to weight loss achieved with diet and exercise alone.
ARRA funding has accelerated the pace of this research, enabling investigators to obtain more data, more quickly, that ultimately will help individuals and their health care providers make critical treatment decisions.
  • Comparing Surgical Methods for Effectiveness in Treating Moderate Obesity and Type 2 Diabetes: Researchers used ARRA support to launch pilot studies to compare the effects of different treatments for individuals with moderate levels of obesity and type 2 diabetes. Treatments included two different forms of bariatric surgery, gastric bypass and gastric banding, and a lifestyle weight loss program of diet and physical activity.4 The researchers sought to determine the feasibility of assigning participants to the different treatments in a randomized way, and to obtain preliminary information on health effects. Based on progress in recruiting and treating study participants, one of the principal investigators has since received a new grant for longer-term follow-up of the participants, to assess effects on diabetes and other metabolic outcomes.
  • Understanding Risks and Benefits of Bariatric Surgery: With ARRA supplementary funding, researchers have enhanced ongoing observational studies of the risks and benefits of bariatric surgery: 1) the Longitudinal Assessment of Bariatric Surgery, LABS, in adults, and 2) the Teen-LABS study, in adolescents.5 For example, ARRA funding has made possible remote (home-based) study visits for LABS participants who are unable to return to the original research center, enabling valuable follow-up. The researchers have also improved the evaluation of sleep apnea, a breathing disorder common in obesity, with the addition of polysomnogram technology to analyze a subset of patients in both studies. Furthermore, the investigators developed a registry for patients with hypothalamic obesity, in order to facilitate research on treating this unusual form of severe obesity, which can result from diverse conditions that impair a part of the brain involved in body weight regulation. ARRA funding has also enabled further analysis of biological samples from participants in both studies.

Contributing NIH Institutes & Centers

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  1. http://www.ncbi.nlm.nih.gov/pubmed/22253364, http://www.ncbi.nlm.nih.gov/pubmed/22253363
  2. 1RC2DK088661-01 - KAPLAN, LEE MICHAEL - MASSACHUSETTS GENERAL HOSPITAL - BOSTON - MA
    5RC2DK088661-02 - KAPLAN, LEE MICHAEL - MASSACHUSETTS GENERAL HOSPITAL - BOSTON - MA
    3U24DK059637-09S1 - WASSERMAN, DAVID H - VANDERBILT UNIVERSITY MED CTR - NASHVILLE - TN
    http://www.ncbi.nlm.nih.gov/pubmed/22492873
  3. 1RC1DK087307-01 - HAVEL, PETER J - UNIVERSITY OF CALIFORNIA DAVIS - DAVIS - CA
    5RC1DK087307-02 - HAVEL, PETER J - UNIVERSITY OF CALIFORNIA DAVIS - DAVIS - CA
    http://www.ncbi.nlm.nih.gov/pubmed/22719048
  4. 1RC1DK086037-01 - COURCOULAS, ANITA P - UNIVERSITY OF PITTSBURGH AT PITTSBURGH - PITTSBURGH - PA
    5RC1DK086037-02 - COURCOULAS, ANITA P - UNIVERSITY OF PITTSBURGH AT PITTSBURGH - PITTSBURGH - PA
  5. 3U01DK066557-07S1 - BELLE, STEVEN H. - UNIVERSITY OF PITTSBURGH AT PITTSBURGH - PITTSBURGH - PA
    3U01DK066557-06S1 - BELLE, STEVEN H. - UNIVERSITY OF PITTSBURGH AT PITTSBURGH - PITTSBURGH - PA
    3U01DK066555-06S3 - WOLFE, BRUCE M - OREGON HEALTH AND SCIENCE UNIVERSITY - PORTLAND - OR
    3U01DK066555-06S1 - WOLFE, BRUCE M - OREGON HEALTH AND SCIENCE UNIVERSITY - PORTLAND - OR
    3U01DK066555-06S2 - WOLFE, BRUCE M - OREGON HEALTH AND SCIENCE UNIVERSITY - PORTLAND - OR
    3U01DK072493-05S2 - INGE, THOMAS HARRIS - CHILDREN'S HOSPITAL MEDICAL CENTER CINCI - CINCINNATI - OH
    3U01DK072493-05S1 - INGE, THOMAS HARRIS - CHILDREN'S HOSPITAL MEDICAL CENTER CINCI - CINCINNATI - OH
    3U01DK072493-04S1 - INGE, THOMAS HARRIS - CHILDREN'S HOSPITAL MEDICAL CENTER CINCI - CINCINNATI - OH