Does Gastric Bypass Surgery Result in Metabolic Benefits Outside of Weight Loss?

Several trials have shown bariatric surgery is more effective than medical therapy for type 2 diabetes (T2D), while some surgical procedures involving bypass of the upper gastrointestinal tract may have therapeutic effects on glycemic control.

However, due to conflicting results among studies and because data on these factors are limited, effects of gastric bypass, independent of weight loss, on the major factors involved in the pathogenesis of T2D are unclear.

To determine whether gastric bypass confers therapeutic metabolic effects independent of weight loss in this population, researchers conducted a matched prospective cohort study. Results were published in The New England Journal of Medicine.

Investigators found that in individuals with T2D and comorbid obesity, the metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself, but the procedure had no evident clinically important effects independent of weight loss.

In total, 22 individuals with obesity and T2D were included in the study. Researchers compared effects induced by Roux-en-Y gastric bypass (surgery group, n = 11) and low-calorie diet therapy (diet group, n = 11) before and after weight loss.

Change in hepatic insulin sensitivity was the primary outcome for the trial. Secondary outcomes included changes in insulin sensitivity in muscle and adipose tissue, beta-cell function, metabolic response to mixed-meal ingestion, 24-hour glucose, free fatty acid and insulin profiles, and body composition.

“Participants in the diet group received weekly education sessions on dietary practices and guidance on dietary behavior,” authors wrote, while “all meals were provided throughout the study as liquid shakes and pre-packaged entrees.”

Patients who underwent surgery also had weekly consultations with a dietician to monitor body weight and adjust dietary intake to meet their weight loss goals.

To provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiologic range of plasma insulin concentrations, investigators used a 3-stage hyperinsulinemic euglycemic pancreatic clamp to control portal and systemic plasma insulin concentrations.

Researchers also “infused octreotide during the clamp procedure to block endogenous insulin secretion in order to ensure that similar portal vein insulin concentrations were achieved before and after weight loss.”

Mean (SD) age of individuals in the diet group was 54 (9) years and the group had a mean time of 9.1 (5.6) years since diagnosis of diabetes. In comparison, mean age of those in the surgery group was 49 (12) years with a mean time since diabetes diagnosis of 9.6 (9.6) years.

Analyses revealed:

• Mean weight loss was 17.8 (1.2%) (range, 16.1 to 20.4) in the diet group and 18.7 (2.5%) (range, 16.0-24.4) in the surgery group
• Diabetes medication score decreased from 0.93 (0.55) to 0.23 (0.29) (mean difference, −0.70; 95% CI, −1.06 to −0.33) in the diet group and from 1.64 (1.15) to 0.60 (0.78) (mean difference, −1.04; 95% CI, −1.70 to −0.40) in the surgery group, with no significant difference between the groups
• Weight loss decreased the integrated 24-hour plasma glucose and insulin concentrations by about 40% from baseline in both the diet and surgery groups
• 4 participants in the diet group and 2 in the surgery group reached glycated hemoglobin levels lower than 6% without diabetes medications
• Insulin sensitivity in the liver, skeletal muscle, and adipose tissue increased after weight loss in both the diet and surgery groups, with no significant differences between the groups
• Weight loss caused changes in the composition of the gut microbiome in both treatment groups, but the changes were greater in the surgery group than in the diet group
• 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

“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,” researchers wrote.

The findings emphasized the therapeutic effects of weight loss on metabolic function and illustrate that metabolic benefits of gastric bypass surgery are probably the result of weight loss alone, authors said.

Investigators hypothesize the improved 24-hour metabolic profile was caused by improvements in beta-cell function and multiorgan insulin sensitivity, in addition to a decrease from baseline total carbohydrate and energy intake.

“The similar findings in participants in the 2 groups challenge the current belief that upper gastrointestinal bypass has clinically meaningful effects on key metabolic factors involved in glucose homeostasis and the pathogenesis of diabetes that are independent of weight loss,” authors concluded. “However, the difficulty in achieving successful long-term weight loss with lifestyle therapy often renders gastric bypass surgery far more effective than diet therapy for most patients with obesity and T2D.”

Reference

Yoshino M, Kayser BD, Yoshino J, et al. Effects of diet versus gastric bypass on metabolic function in diabetes. N Engl J Med. Published online August 19, 2020. doi:10.1056/NEJMoa2003697