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

Abstract

Structured Abstract Objective To compare bariatric surgery vs. intensive medical weight management (MWM) in patients with type 2 diabetes (T2DM) who do not meet current NIH criteria for bariatric surgery. To assess whether the soluble form of receptor for advanced glycation endproducts (sRAGE) is a biomarker to identify patients most likely to benefit from surgery. Summary Background Data There are few studies comparing surgery to MWM for patients with T2DM and BMI < 35. Methods 57 patients with T2DM and BMI 30–35 who otherwise met criteria for bariatric surgery were randomized to MWM vs. surgery (bypass, sleeve or band, based on patient preference). The primary outcomes assessed at 6 months were change in insulin resistance (HOMA-IR) and diabetes remission. Secondary outcomes included changes in HbA1c, weight, and sRAGE. Results The surgery group had improved HOMA-IR (−4.6 vs. +1.6; p=0.0004) and higher diabetes remission (65% vs. 0%, p<0.0001) than the MWM group at 6 months. Compared to MWM, the surgery group had lower HbA1c (6.2 vs. 7.8, p=0.002), lower fasting glucose (99.5 vs. 157; p=0.0068) and fewer T2DM medication requirements (20% vs. 88%; p<0.0001) at 6 months. The surgery group lost more weight (7.0 BMI decrease vs. 1.0 BMI decrease, p<0.0001). Higher baseline sRAGE was associated with better weight loss outcomes (r=−0.641; p=0.046). There were no mortalities. Conclusions Surgery was very effective short-term in patients with T2DM and BMI 30–35. Baseline sRAGE may predict patients most likely to benefit from surgery. These findings need to be confirmed with larger studies. ClinicalTrials.gov ID: NCT01423877

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations

“…2A). Numerous RCTs with postoperative follow-up ranging between 1 and 5 years have consistently documented sustained diabetes remission in 30-63% of patients (LoE IB) (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Available data suggest an erosion of diabetes remission over time: 35-50% or more of patients who initially achieve remission of diabetes eventually experience recurrence.…”

“…Beyond improving glycemia, bariatric/ metabolic surgery has been shown to confer additional health benefits in RCTs, including greater reductions compared with medical/lifestyle interventions in other CVD risk factors (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), and enhancements in quality-of-life measures (LoE IB) (15,19,20). Improvements in other critical outcomes, such as micro-and macrovascular complications of diabetes, CVD, cancer, and death, have been observed only in nonrandomized studies (LoE IIA) (3,52,57,(61)(62)(63)(64)(65).…”

“…The GI tract is an important contributor to normal glucose homeostasis (35), and mounting evidence, especially over the past decade, has demonstrated benefits of bariatric/metabolic surgery to treat and prevent T2D (3,5,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(51)(52)(53). Beyond inducing weight loss-related metabolic improvements, some operations engage mechanisms that improve glucose homeostasis independent of weight loss (6), such as changes in gut hormones, bile acid metabolism, microbiota, intestinal glucose metabolism, and nutrient sensing (5,6,(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

“…Since DSS-I, a substantial body of additional evidence has accumulated, including from numerous randomized clinical trials (RCTs), demonstrating that bariatric/ metabolic surgery achieves superior glycemic control and reduction of cardiovascular risk factors in obese patients with T2D compared with various medical/lifestyle interventions (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Further research on mechanisms of action of these procedures (5,6,(26)(27)(28)(29)(30)(31)(32)(33)(34) has corroborated evidence in animal studies demonstrating an important role for the GI tract in glucose homeostasis (35), providing a biological rationale for the use of GI-based interventions to treat T2D.…”

Could Advanced Glycation End Products Explain the Poor Response to Controlled Ovarian Hyperstimulation in Obese Women?

“…Additionally, a study by Diamanti-Kandarakis, et al showed that long term consumption of AGEs was associated with higher levels of fasting glucose, insulin and serum AGEs, as well as increased AGEs localization and RAGE staining in rat ovarian tissue [34]. Interestingly, diet-induced weight loss has been shown to increase serum sRAGE levels [26,78], and higher baseline sRAGE was associated with better weight loss outcome following bariatric surgery [79].…”