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ARRA Investments in Bariatric Surgery

Public Health Burden
Obesity has risen to epidemic levels in the U.S., with approximately one third of U.S. adults considered to be obese based on body mass index, a measure of weight relative to height.  Furthermore, there have been significant increases in the prevalence of extreme obesity.  Individuals who are severely obese are most at risk for serious health problems such as developing type 2 diabetes and other adverse health conditions.  Used as a treatment for extreme obesity, bariatric surgical procedures modify the digestive tract to limit the amount of food that can enter the stomach, decrease absorption of nutrients, or both.  Currently, bariatric surgery appears to be the only intervention that consistently results in substantial and sustained weight loss in people who are extremely obese, and it has been linked to remission of diabetes, decreases in cardiovascular risk factors, and a significant reduction in mortality over time.  During the last decade, the number of bariatric surgical procedures performed has increased significantly.  Like most surgical procedures, however, bariatric surgery presents risks of complications that must be considered along with potential benefits when an individual is deciding whether to undergo the procedure.

Comparative Effectiveness of Bariatric Surgery Procedures for Treating Type 2 Diabetes
Aside from significant and sustained weight loss, bariatric surgery patients with type 2 diabetes have shown significant reduction in diabetes medications usage and remission of high blood sugar levels.  Surgical interventions in people with relatively recent onset type 2 diabetes appear to result in increased rates of resolution compared to people with longer disease duration.  These findings suggest that bariatric surgery may represent a potential therapeutic management strategy for type 2 diabetes; however, several questions remain that require well-controlled studies to more completely evaluate the efficacy of bariatric surgery.  A variety of ARRA-funded grants are exploring this topic, including pilot studies designed for collecting data to inform larger trials:
  • A pilot study comparing different bariatric surgical procedures with a non-surgical weight loss program in moderately obese people with type 2 diabetes.  The endpoints will include measuring markers for heart health.1
  • A pilot study comparing gastric bypass, gastric banding, and a structured, non-surgical weight loss program for the treatment of type 2 diabetes in moderately obese people.  Outcome measures include: resolution of diabetes, function of insulin-producing cells, and body composition.2
  • A pilot study comparing two different bariatric surgical procedures with each other and with a non-surgical weight loss program for treating moderately obese people with type 2 diabetes.  In addition to measuring diabetes control, the study will collect data from food records and an economic analysis.3
Mechanisms of Bariatric Surgery
Among the current therapies for obesity, various forms of bariatric surgery have proven to be exceptionally effective and durable. Recent studies have demonstrated that these operations work primarily by affecting the physiological regulation of body weight. They affect multiple aspects of metabolic function, in some cases through mechanisms independent of weight loss or diminished food intake. These characteristics make use of bariatric surgery as an attractive approach to examining physiological regulation of metabolic function. Using surgery to probe physiological mechanism is complementary to other means of studying these regulatory pathways, such as pharmacological or genetic manipulation. Combining the power of surgical, genetic, nutritional and pharmacological approaches will facilitate greater understanding of the cellular and molecular mechanisms underlying metabolic physiology in normal and disease states. The recent development of rat and mouse models of nearly all of the currently available bariatric surgical procedures will strongly facilitate this effort, but the technical difficulty and high cost of developing and maintaining these models is a formidable barrier to their use.  A number of ARRA-funded grants are exploring this topic:
  • A project facilitated by the Small Animal Metabolic Surgery (SAMS) Resource Core to increase understanding of the cellular and molecular regulation of metabolic function, and to help to identify the mechanisms underlying the therapeutic benefits of bariatric surgery.4
  • A study testing the hypothesis that bariatric surgery in pre-diabetic type 2 diabetic rats delays the onset of type 2 diabetes by influencing the production, secretion, and signaling of gastrointestinal hormones and a fat cell hormone, adiponectin; and by altering bile acid metabolism and intestinal microflora.  The project will also test the hypothesis that bariatric surgery delays the onset of type 2 diabetes by preserving mitochondrial function which deteriorates during the disease development and progression.5
  • A grant to determine whether the key anatomical aspect of bariatric surgery procedures resulting in the resolution of type 2 diabetes is the exposure of the lower intestine to higher concentrations of bile salts.  This will test whether lower intestinal exposure to bile salts is sufficient for improving type 2 diabetes in rats following bariatric surgical procedures.6

  1. 1RC1DK086918-01 -- Comparative effectiveness of medical therapy vs. bariatric surgery for obese T2DM -- Lautz, David (MA)
  2. 1RC1DK086037-01 -- A randomized trial to compare surgical and medical treatments for type 2 diabetes -- Courcoulas, Anita (PA)
  3. 1RC1DK086132-01 -- Lifestyle modification versus bariatric surgery for type 2 diabetes -- Sarwer, David (PA)
  4. 1RC2DK088661-01 -- Small Animal Metabolic Surgery (SAMS) Resource Core -- Kaplan, Lee Michael (MA)
  5. 1RC1DK087307-01 -- Surgical Amelioration of Type 2 Diabetes: Hormones, Microbiota and Mitochondria --Havel, Peter J. (CA)
  6. 1RC1DK086999-01 -- Understanding the Role of Bile as a Mechanism for Improved Glucose Homeostasis Fo -- Strader, April Dawn (IL)

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