Randomized pilot trial of bariatric surgery versus intensive medical weight management on diabetes remission in type 2 diabetic patients who do NOT meet NIH criteria for surgery and the role of soluble RAGE as a novel biomarker of success.

Up to 78% of patients with type 2 diabetes mellitus (T2DM) may experience diabetes remission within two years after bariatric surgery.1 Currently, only patients with T2DM and body mass index (BMI) above 35 kg/m2 are eligible for bariatric surgery. This is based on the 1991 National Institutes of Health (NIH) Guidelines and has been endorsed by the Center for Medicare and Medicaid Services.2 Patients with T2DM and BMI < 35 are primarily offered intensive medical weight management (MWM), including pharmacotherapy and nonsurgical weight loss strategies. Millions of patients with T2DM have BMI < 35—yet metabolic surgery is not an option for them.3 There is emerging evidence supporting the use of bariatric surgery to treat diabetes in less obese (BMI < 35) patients. However, there are very few randomized trials. The Agency for Healthcare Research and Quality (AHRQ) recently identified this area as a research priority for comparative effectiveness research.4 The NIH is unlikely to change the bariatric surgery guidelines for patients with T2DM without additional evidence to support such a change.5 There is also an overall lack of treatment data in underrepresented minorities (especially Hispanics and non-Hispanic African-Americans) with T2DM, who are disproportionately affected by diabetes-related complications and mortality. Our municipal health care system serves a substantial number of these “hard-to-reach” minorities. The receptor for advanced glycation end-products (RAGE) binds multiple ligand families linked to hyperglycemia. Activation of RAGE plays a major role in the pathogenesis of diabetic vascular complications via activation of the nuclear factor κ β pathway.6 Recent data indicate that mice devoid of RAGE who are fed high fat diet are protected from diet-induced obesity and that the treatment of diabetic mice with a soluble form of RAGE (sRAGE) results in significantly reduced body weight gain vs. vehicle-treated animals.7 Interestingly, sRAGE already circulate in human plasma. sRAGE acts as a decoy to prevent an interaction between advanced glycation end-products and RAGE and subsequent RAGE ligand-mediated effects on obesity and diabetes complications.8 Therefore, levels of sRAGE may be innate biomarkers of vulnerability to obesity and diabetes and/or their severity.9 The purpose of this study was two-fold: 1) to conduct a pilot randomized trial to compare bariatric surgery to MWM in patients with T2DM and BMI 30–35 who otherwise met NIH criteria for surgery, and 2) to assess the role of sRAGE as a biomarker for predictor of success after surgery. Due to the fact that insurance companies typically cover bariatric surgery in patients with T2DM and BMI > 35, we partnered with our municipal healthcare system’s primary insurer, who agreed to cover the costs of the surgery as part of this research project.