Weight loss by either surgery or diet key to better metabolic health in diabetes

For individuals with type 2 diabetes, losing weight is everything when it comes to improving the metabolic function, and it matters little whether this is achieved by dieting or undergoing bariatric surgery, according to a small study.

“We found nearly identical benefits of matched weight loss induced by gastric bypass or diet alone on multiorgan insulin sensitivity, beta-cell function, 24-hour plasma glucose and insulin profiles, and body composition,” the investigators said.

In a group of 22 patients (15 women) with obesity and type 2 diabetes (mean duration, 9 years), the  mean weight loss achieved was 18.7 percent with the surgery group (n=11; mean age, 49 years) and 17.8 percent with the diet group (n=11; mean age, 54 years).

This weight improvement led to a similar increase in suppression of glucose production during stage 1 of a 9-hour, three-stage hyperinsulinaemic euglycaemic pancreatic clamp procedure—7.02 and 7.04 μmol/kg of fat-free mass per minute in the surgery and diet groups, respectively. Stage 2 results still did not differ, with mean suppression of glucose production increasing by 5.37 and 5.39 μmol/kg of fat-free mass per minute from baseline. [N Engl J Med 2020;383:721-732]

Weight loss by either approach was also associated with many other benefits. Insulin-stimulated glucose disposal increased from 29.4 to 54.5 μmol per kilogram of fat-free mass per minute with surgery and from 30.5 to 61.6 μmol per kilogram of fat-free mass per minute with diet, with no significant between-group difference.

Both groups showed a comparable increase in beta-cell function (insulin secretion relative to insulin sensitivity; 1.11 units with surgery vs 1.83 units with diet), as well as decreases in the areas under the curve for 24-hour plasma glucose and insulin levels.

Likewise, body composition, 24-hour plasma glucose, and glycated haemoglobin levels equally improved in the two groups. The diabetes medication score decreased by 0.70 with diet and by 1.04 with surgery, with four and two participants in the respective groups reaching the glycated haemoglobin target level without diabetes medications.

“The results from our study underscore the profound effect that marked weight loss can have on metabolic function in people with diabetes,” the investigators pointed out.

“The similar findings … 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 added

But there are still cases where surgery works when diets don’t, the investigators acknowledged. “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.”

They also noted that gastric bypass is believed to confer weight-loss independent benefits, and this belief is predicated on several factors including decreased plasma branched-chain amino acids and their acylcarnitines, increased circulating bile acids, and alterations in the gut microbiome. [Sci Transl Med 2011;3:80re2; Obesity 2009;17:1671-1677; Diabetes 2010;59:3049-3057; Pharmacogenomics J 2013;13:514-522]

In a linked commentary, Drs Clifford Rosen from Maine Medical Center Research Institute in Scarborough, US, and Julie Ingelfinger from Massachusetts General Hospital in Boston, US, pointed out important study limitations. [N Engl J Med 2020;383:777-778]

For the most part, the trial was small and not randomized, and there was potentially some confounding due to differences between patients choosing one weight-loss approach over the other. Additionally, all patients in the surgery group underwent Roux-en-Y, Rosen and Ingelfinger noted, “so extrapolating those findings to the improved glucose tolerance associated with vertical sleeve gastrectomy, currently the most frequent procedure, must be done with caution.”

“Nevertheless, 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,” they wrote.