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Patients with obesity and type 2 diabetes saw significant improvements in metabolic function after weight loss, regardless of whether they achieved the latter with diet or bariatric surgery, researchers reported.

Looking at stage one of a 9-hour, three-stage hyperinsulinemic euglycemic pancreatic clamp procedure, weight loss was tied to a 7.04 μmol/kg of fat-free mass per minute (95% CI 4.74-9.33) increase in average suppression of glucose production for those who lost weight with diet alone, according to Mihoko Yoshino, MD, of Washington University School of Medicine in St. Louis, and colleagues.

Mean suppression of glucose production from baseline increased by 7.02 μmol/kg of fat-free mass per minute (95% CI 3.21-10.84) in those who lost weight via Roux-en-Y gastric bypass (RYGB) surgery, they reported in the .

And during stage two of the clamp procedure, increases in mean suppression of glucose production still weren't significantly different between diet and surgery patients, as these patients saw increases by 5.39 (95% CI 2.44-8.34) and 5.37 (95% CI 2.41-8.33) μmol/kg of fat-free mass per minute in the two groups, respectively.

Both methods of weight loss also resulted in increased insulin-stimulated glucose disposal: from 30.5 to 61.6 μmol/kg of fat-free mass per minute with diet alone, and from 29.4 to 54.5 μmol/kg of fat-free mass per minute with RYGB.

An increase in β-cell function -- measured as β-cell glucose sensitivity by the ratio of postprandial insulin secretion rate to postprandial plasma glucose -- also was noted following weight loss by either method.

Specifically, β-cell function increased by 1.83 units (95% CI 1.22-2.44) in those who lost weight with diet alone, while those who underwent RYGB saw mean increases of 1.11 units (95% CI 0.08-2.15), also with no significant differences between groups.

Decreases in the areas under the curve for 24-hour plasma glucose, as well as insulin levels, were seen equally with both methods.

"We were disappointed, but not surprised," Samuel Klein, MD, also of Washington University, told MedPage Today. "We know that weight loss alone has profound beneficial effects on metabolic health. The problem is that it is very difficult for most people with obesity to lose weight and maintain long-term weight loss."

"In fact, the effect of RYGB surgery on body weight is what makes this procedure so fascinating, and we do not understand why RYGB reduces the drive to eat and is so successful in producing long-term weight loss," he noted.

"Even though weight loss, itself, is the primary mechanism responsible for the beneficial effects of RYGB surgery, this does not diminish the importance of RYGB as a therapy for patients with obesity and type 2 diabetes that improves health and reduces or even completely eliminates the need for diabetes medications," Klein emphasized, listing some of the many metabolic benefits of RYGB, such as improvements in multi-organ insulin sensitivity, β-cell function, and 24-hour blood glucose and insulin profiles.

Designed as a matched prospective cohort study, the analysis included 22 adults with obesity and type 2 diabetes: 11 who lost weight via low-calorie diet alone and 11 who underwent RYGB. On average, participants lost 17.8% and 18.7% of their body weight in the diet and surgery groups, respectively. Both groups were weight-matched with each other to 18% of weight loss.

The three-stage hyperinsulinemic euglycemic pancreatic clamp procedure involved an infusion of stable isotope tracers, octreotide to block insulin secretion, and insulin at increasing rates every 3 hours. Following this procedure, the participants were assessed 2 weeks later with a 7-hour mixed-meal test to measure postprandial glucose and insulin kinetics, 24-hour plasma glucose, free fatty acid, and insulin profiles.

Klein explained that it's typically believed that RYGB has metabolic benefits independent of the weight loss -- attributable specifically to the actual surgery -- reinforced by the postoperative high type 2 diabetes remission rates. "This is an important concept, because it implies that bypassing the upper part of the intestinal tract has novel therapeutic metabolic effects and has stimulated research trying to find the mechanism(s) responsible for this effect."

However, NEJM associate editor Clifford Rosen, MD, and deputy editor Julie Ingelfinger, MD, pointed out in an that the study was limited by the small number of participants, but also by the fact that only RYGB procedures were included. Therefore, these findings shouldn't be generalized to apply to vertical sleeve gastrectomy, which, as of late, is the most popular bariatric procedure, they wrote.

"Nevertheless, this study confirms the pathogenic nature of obesity in driving insulin resistance and, ultimately, type 2 diabetes," Rosen and Ingelfinger concluded, adding that the study ultimately "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."

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