Weight Loss Benefit in Diabetes Is Similar via Surgery or Diet

Miriam E. Tucker

August 19, 2020

The metabolic benefits achieved with weight loss for patients with type 2 diabetes appear to be similar whether achieved via diet or gastric bypass surgery, according to new research.

The findings, from a small study of 22 people with type 2 diabetes and obesity, were published online August 19 in The New England Journal of Medicine (NEJM). The study was conducted by Mihoko Yoshino, MD, PhD, of Washington University School of Medicine, St. Louis, and colleagues.

Among 11 patients in each group who experienced comparable degrees of weight loss (~18%), there were very similar benefits in multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition.

"The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes," Yoshino and colleagues write.

"The similar findings in participants in the two 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," they add.

However, they acknowledge, "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 type 2 diabetes."

"This study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes; furthermore, it delivers a straightforward and important message for both clinicians and patients — reducing adipose tissue volume, by whatever means, will improve blood glucose control in persons with type 2 diabetes," state the authors of an accompanying editorial.

Asked to comment, Matthew M. Hutter, MD, president of the American Society for Metabolic and Bariatric Surgery and professor of surgery at Harvard Medical School and the Massachusetts General Hospital, Boston, Massachusetts, told Medscape Medical News that the study was "very elegant" and "well-designed."

However, he pointed out, "The reality is diet alone has been shown over and over that it's not sustainable. For a very small few it is, but for the vast majority, that's not the case."

Hutter also noted that the research was conducted in a laboratory setting and that the diet group was given prepackaged food. Therefore, the study "doesn't look at how effective [dieting] is in the real world."

Bariatric surgery, on the other hand, "is very effective for treating type 2 diabetes. It's a good long-term solution."

No Significant Differences in Multiple Parameters

The nonrandomized prospective cohort study began with 33 adults with obesity and type 2 diabetes, of whom 18 received weekly diet education sessions and prepackaged food, and 15 underwent Roux-en-Y gastric bypass procedures. Seven in the diet group and four in the surgery group were withdrawn from the study because of a failure to achieve the target of 16% to 18% loss of body weight.

Of those remaining in the study, mean weight loss at around 4 months was 17.8% of body weight for the 11 in the diet group and 18.7% for the 11 in the surgery group. For the diet group, the mean age was 54 years, and the mean duration of diabetes was 9.1 years; for the surgery group, the mean age was 49 years, and the mean duration of diabetes 9.6 years.

A three-stage hyperinsulinemic euglycemic pancreatic clamp was used to control both portal and systemic plasma insulin concentrations to provide a reliable assessment of hepatic, muscle, and adipose tissue insulin sensitivity across a physiologic range of plasma insulin concentrations. In both treatment groups, similar improvements were seen in hepatic, adipose tissue, and skeletal muscle insulin sensitivity

Both groups experienced a similar drop in the use of diabetes medications. Four individuals in the diet group and two in the surgery group achieved A1c levels below 6.0% without any medications.

After ingestion of identical mixed meals, 4-hour areas under the curve (AUC) for plasma glucose and insulin were lower after weight loss than before for both groups, although the decrease in glucose was greater in the diet group.

Postprandial glucose peaks were greater in the surgery group as well, owing to an increase in the rate of glucose delivery into the circulation.

Weight loss was associated with decreased total AUC for glucose, free fatty acids, insulin, and insulin secretion to similar degrees in both groups.

However, there were differences in several factors that have been attributed to the effects of bariatric surgery independently of weight loss. These include a greater decrease in 24-hour plasma branched-chain amino acid and C3 and C5 acylcarnitine concentrations after weight loss in the surgery group than in the diet group.

Plasma bile acid levels after weight loss dropped from baseline in the diet group but rose in the surgery group. Although microbiome changes occurred in both groups, they were more pronounced with weight loss following surgery.

Study Limitations: Small, Not Randomized, Long Diabetes Duration

The authors acknowledge some of the study's limitations, including the fact that it wasn't randomized and there was a large number of dropouts, although they say that the method used to assess the primary outcome can detect small differences even in a few patients.

The editorialists ― endocrinologist Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough, and pediatric nephrologist and deputy NEJM editor Julie R. Ingelfinger, MD, of Massachusetts General Hospital, Boston ― point out that today, more sleeve gastrectomies are performed than Roux-en-Y bypass procedures.

However, Hutter said that gastric bypass procedures are still being performed, that both procedures are effective and safe, and that for patients with diabetes, the bypass tends to be somewhat more effective than sleeve gastrectomy.

He also qualified: "What phase you're in is critical. Here, the 18% [weight loss] is still early in the track for bariatric surgery. They could still be losing weight after that. The diet groups could have been in the plateau or regain phase. Those [numbers] could look very different with time."

In addition, he noted that the relatively long average duration of diabetes in the study participants makes the success of bariatric surgery less likely.

"The pancreas burns out, and the tissues become less insulin sensitive. I would have wanted to stratify the patients into early vs later disease, but you would need a larger sample size to do that," he said.

Hutter noted, "I thought the study was very interesting. It just amazes me that 60 years after the gastric bypass procedure was invented, we're still trying to figure out how it works."

Hutter is a consultant for Vicarious Surgical and has received honoraria from Ethicon, Medtronic, and Olympus.

N Engl J Med. Published online August 19, 2020. Abstract, Editorial

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