Clinical Pearls & Morning Reports
Yoshino et al. assessed whether gastric bypass conferred therapeutic metabolic effects independent of weight loss in people with obesity and type 2 diabetes by comparing the effects of marked weight loss induced by Roux-en-Y gastric bypass with the effects of the same weight loss induced by a low-calorie diet alone on metabolic function. Read the NEJM Original Article here.
Q: What observation raised the question of whether gastric bypass might have unique therapeutic effects on glycemic control?
A: Randomized clinical trials have shown that bariatric surgery is more effective than medical therapy for treatment of type 2 diabetes. Moreover, several studies suggest that surgical procedures that involve bypass of the upper gastrointestinal tract, such as Roux-en-Y gastric bypass, have unique therapeutic effects on glycemic control, as evidenced by the higher incidence of diabetes remission after gastric bypass than after procedures that maintain intestinal continuity. However, the results from such studies are confounded by differences in weight loss among patients who undergo the procedures.
Q: What metabolic factors were assessed in the trial by Yoshino et al.?
A: The authors compared the effects of marked weight loss induced by Roux-en-Y gastric bypass with the effects of the same weight loss induced by a low-calorie diet alone on hepatic insulin sensitivity (primary outcome) and muscle and adipose tissue insulin sensitivity; beta-cell function; the metabolic response to mixed-meal ingestion; 24-hour plasma glucose, free fatty acid, and insulin profiles; and body composition. The authors also evaluated several factors purported to be associated with benefits of gastric bypass independent of weight loss.
A: After marked weight loss induced by either diet therapy or gastric bypass, there were considerable improvements in body composition (body fat mass, intraabdominal adipose tissue volume, and intrahepatic triglyceride content); 24-hour plasma glucose, free fatty acid and insulin profiles; beta-cell function; and insulin sensitivity in the liver, skeletal muscle, and adipose tissue, with no significant differences between the groups in any of these variables. These results underscore the potent therapeutic effects of weight loss on metabolic function and show that the metabolic benefits of gastric bypass surgery are probably the result of weight loss alone.
A: Several mechanisms have been purported to cause metabolic benefits of gastric bypass that are independent of weight loss, including decreased plasma branched-chain amino acids and their acylcarnitines, increased circulating bile acids, and alterations in the gut microbiome. The authors found that patients in the surgery group had a greater decline in plasma concentrations of branched-chain amino acids and C3 and C5 acylcarnitines and a greater increase in plasma bile acids than patients in the diet group — a finding consistent with results from previous studies. The changes observed in the gut microbiome of persons in the surgery group are also consistent with the results from most studies and were much greater than the changes observed in the diet group. These results confirm that gastric bypass causes alterations in specific plasma metabolites and the gut microbiome that are independent of weight loss but showed that these changes were not associated with greater improvements in metabolic function.