Improvements in Glycemic Control After Gastric Bypass Occur Despite Persistent Adipose Tissue Inflammation

Objective: Type 2 diabetes commonly goes into remission following Roux-en-Y gastric bypass (RYGB). As the mechanisms remain incompletely understood, a reduction in adipose tissue inflammation may contribute to these metabolic improvements. Therefore, whether RYGB reduces adipose tissue inflammation compared with equivalent weight loss from an intensive lifestyle intervention was investigated. Methods: Sixteen people with obesity and type 2 diabetes were randomized to RYGB or lifestyle intervention. Fasting blood and subcutaneous abdominal adipose tissue were obtained before and after the loss of similar to 7% of baseline weight. Adipose tissue inflammation was assessed by whole-tissue gene expression and flow cytometry-based quantification of tissue leukocytes. Results: At 7% weight loss, insulin and metformin use were reduced among the RYGB but not the Lifestyle cohort, while fasting glucose and insulin declined in both. Adipose tissue inflammation increased modestly after RYGB and to a similar extent following nonsurgical weight loss. In both groups, the number of neutrophils increased severalfold (P < 0.001), mRNA levels of the proinflammatory cytokine interleukin-1 beta increased (P = 0.037), and mRNA expression of the anti-inflammatory and insulin-sensitizing adipokine adiponectin decreased (P = 0.010). Conclusions: A reduction in adipose tissue inflammation is not one of the acute weight loss-independent mechanisms through which RYGB exerts its antidiabetes effects.