Weight Loss, Not Surgery, Responsible for Metabolic Benefits Following Gastric Bypass

Samuel Klein, MD

Perspective from new research by investigators at Washington University School of Medicine is providing an overview of the clinical benefits of weight loss from gastric bypass surgery versus diet alone in obese patients with type 2 diabetes.

Results of the study indicated the metabolic benefits seen after Roux-en-Y gastric bypass, such as lower blood sugar and reduction in the need for antidiabetic medications, were related to the weight loss incurred by the surgery and the procedure itself did not provide any unique therapeutic effects.

“We found gastric bypass surgery improves metabolic function by causing weight loss. There were no differences in the reduction of diabetes medications or in the rate of diabetes remission between surgery patients and those who lost equivalent amounts of weight through diet alone,” principal investigator Samuel Klein, MD, director of Washington University's Center for Human Nutrition, in a statement from Washington University.

As the prevalence of obesity and obesity-related disease has increased in the US in recent decades, so has and frequency of gastric bypass surgeries. Even with multiple trials examining the effects of gastric bypass on various aspects of a patient’s wellbeing, knowledge gaps related to the effects of surgery independent of weight loss have resulted in debate over the potential of a unique therapeutic impact from gastric bypass surgery on metabolic health.

To learn more about the effects of gastric bypass compared to diet alone, Klein and a team of colleagues designed the National Institutes of Health-sponsored study as a matched prospective cohort study in 22 patients with obesity and diabetes before and after matched weight loss induced through Roux-en-Y gastric bypass or diet alone.

Conducted between November 2014-October 2018, the study included patients who reached a marked weight loss goal of 16-24% through a weight loss intervention that included a low calorie diet consisting of liquid shakes and repacked entrees along with weekly education sessions or Roux-en-Y gastric bypass.

The primary outcome of the study was change in hepatic insulin sensitivity and the secondary outcomes were 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.

In an effort to reduce the impact of variables on outcomes, participants were required to discontinue GLP-1 RA therapies 2 weeks before the study. Additionally, oral diabetes medications were to be discontinued 3 days prior and insulin was to be discontinued 1 day prior to the beginning of the study.

Investigators identified 33 patients for inclusion in their study—18 in the diet group and 15 in the surgery group. Of these, 7 from the diet group and 4 from the surgery group withdrew or were withdrawn because they did not achieve the weight loss target. The cohort included in the final analyses consisted of 11 patients in each group.

The diet group consisted of 4 men and 7 women with a mean age of 54±9 years and a mean time since diabetes diagnosis of 9.1±5.6 years. At the end of the study, this group achieved a mean weight loss of 17.8±1.2%. The surgery group consisted of 3 men and women with a mean age of 49±12 years and a mean time since diabetes diagnosis of 9.6±9.6 years. At the end of the study, this group achieved a mean weight loss 18.7±2.5%.

Results of the study indicated weight loss was associated with increases in mean suppression of glucose production from baseline. Specifically, diet alone was associated with increases of 7.04 μmol per kilogram of fat-free mass per minute (95% CI, 4.74-9.33). In the surgery group, investigators observed increases of 7.02 μmol per kilogram of fat-free mass per minute (95% CI, 3.21-10.84) during clamp stage 1. During clamp stage 2, investigators reported increases of 5.39 (95% CI, 2.44-8.34) and 5.37 (95% CI, 2.41-8.33) μmol per kilogram of fat-free mass per minute in the two groups, respectively. Investigators pointed out there were no significant differences between the groups.

Results also indicated weight loss was associated with increased insulin-stimulated glucose disposal. These increases ranged from 30.5±15.9 to 61.6±13.0 μmol per kilogram of fat-free mass per minute in the diet group and from 29.4±12.6 to 54.5±10.4 μmol per kilogram of fat-free mass per minute in the surgery group—there were no significant differences between the study groups.

Investigators found no significant differences between the 2 groups when assessing effects of weight loss on beta-cell function. Weight loss increased function by 1.83 (95% CI, 1.22-2.44) units in the diet group and by 1.11 (95% CI, 0.08 to 2.15) units in the surgery group. Additionally, weight loss decreased the areas under the curve for 24-hour plasma glucose and insulin levels in both groups. Similar to the previous outcomes, investigators noted there were no significant differences observed between the 2 groups.

This study, “Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes,” was published in the New England Journal of Medicine.