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STAMPEDE

STAMPEDE: ghrelin normal after gastric bypass

Study suggests that ghrelin suppression may play a key role in improved glucose control

Roux-en-Y gastric bypass (RYGB) surgery restored normal regulation of the appetite hormone ghrelin, the latest analysis of the STAMPEDE trial has reported. Bypass patients also lost more abdominal fat and had improved insulin secretion, compared with patients who had sleeve gastrectomy (SG), even though their total weight loss was the same.

The study results, published in the International Journal of Obesity, suggests that ghrelin suppression may play a key role in improved glucose control, as bypass surgery patients had greater suppression of acylated ghrelin two years after surgery and had better metabolic outcomes, including pancreatic beta-cell function.

"Our data highlight plasma acylated ghrelin as a potential modifying factor in RYGB-induced diabetes remission," the authors wrote. "Ghrelin may represent an alternative, or complimentary, endocrine-mediator of diabetes remission, since it is related to metabolic syndrome, obesity, insulin resistance, and insulin secretion capacity."

STAMPEDE

Fifty-three (BMI: 36±3, age: 49±9 years) poorly controlled patients with T2D (HbA1c (glycated hemoglobin): 9.7±2%) were randomised to intensive medical therapy (IMT), IMT+RYGB or IMT+SG and underwent a mixed-meal tolerance test at baseline, 12, and 24 months for evaluation of acylated ghrelin suppression (postprandial minus fasting) and beta-cell function (oral disposition index; glucose-stimulated insulin secretion × Matsuda index). Total/android body fat (dual-energy X-ray absorptiometry) was also assessed.

The results showed that RYGB and SG reduced body fat comparably (15-23 kg) at 12 and 24 months, whereas IMT had no effect. Beta-cell function increased 5.8-fold in RYGB and was greater than IMT at 24 months (p<0.001).

However, there was no difference in insulin secretion between SG vs. IMT at 24 months (p=0.32). Fasting acylated ghrelin was reduced four-fold following SG (p<0.01) and did not change with RYGB or IMT at 24 months.

Acylated ghrelin suppression improved more following RYGB than SG or IMT at 24 months (p=0.01 vs SG, p=0.07 vs IMT). At 24 months, acylated ghrelin suppression was associated with increased postprandial glucagon-like peptide-1 (p<0.02) and decreased android fat (p<0.006).

Prior to the intervention, fasting, post-prandial and acylated ghrelin suppression outcomes were not different across treatment groups.

All treatments lowered post-prandial acylated ghrelin compared with baseline at 12 and 24 months (all p<0.05), and RYGB and gastric-sleeve surgery each lowered post-prandial acylated ghrelin compared with medical therapy alone (p<0.004) at 12 months. Ghrelin levels showed a non-significant trend toward reduction after gastric sleeve surgery compared with RYGB (p<0.08).

The STAMPEDE trial was originally designed to compare glycaemic control outcomes among obese patients with type 2 diabetes treated with either RYGB, gastric sleeve, or no bariatric surgery and medical management.

One-year results from the trial showed that either of the two surgeries plus optimal medical therapy was better than optimal medical therapy alone in controlling type 2 diabetes.

A two-year analysis of the trial, reported in June 2013, showed that while both surgical techniques resulted in similar weight loss at two years, bypass patients had greater losses in android fat and better rates of diabetes remission.

The research was funded by Ethicon Endo-Surgery, the American Diabetes Association, and the National Institutes of Health.

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