Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy

Abstract

Objective: Roux-en-Y gastric bypass (RYGB) produces more durable glycemic control than sleeve gastrectomy (SG) or intensive medical therapy (IMT). However, the contribution of acylated ghrelin (AG), a gluco-regulatory/appetite hormone, to improve glucose metabolism and body composition in patients with type 2 diabetes (T2D) following RYGB is unknown.

Design: STAMPEDE (Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently) was a prospective, randomized controlled trial.

Subjects: Fifty-three (body mass index: 36±3 kg m(-2), age: 49±9 years) poorly controlled patients with T2D (HbA1c (glycated hemoglobin): 9.7±2%) were randomized to IMT, IMT+RYGB or IMT+SG and underwent a mixed-meal tolerance test at baseline, 12, and 24 months for evaluation of AG 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.

Results: 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 AG was reduced fourfold following SG (P<0.01) and did not change with RYGB or IMT at 24 months. AG 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, AG suppression was associated with increased postprandial glucagon-like peptide-1 (r=-0.32, P<0.02) and decreased android fat (r=0.38; P<0.006).

Conclusions: Enhanced AG suppression persists for up to 2 years after RYGB, and this effect is associated with decreased android obesity and improved insulin secretion. Together, these findings suggest that AG suppression is partly responsible for the improved glucose control after RYGB surgery.

Figure 1

The effects of medical therapy vs surgery on absolute and percentage change of AG: fasting (a and b), postprandial (c and d) and suppression (e and f) at 0, 12 and 24 months. To convert ghrelin from fmol ml⁻¹ to pg ml⁻¹, multiply data by 3.37. Data are median ± interquartile range (IQR). Note: at 24 months, SG IQR was equivalent to lower median. *Compared with baseline (P < 0.05). ^€Compared with IMT and GB at 12 months (P < 0.001). ^¥Compared with 0 and 12 months IMT (P < 0.001). ^†Compared with GB at 12 months (P = 0.07). ^Compared with IMT at 12 months (P < 0.004). ^$Compared with IMT and GB at 24 months (P < 0.001). ^‡Compared with IMT at 24 months (P < 0.05). %Compared with IMT 24 months (P = 0.07). ^#Compared with SG 24 months (P < 0.003).

Figure 2

Correlation between the change in fasting (a and b), postprandial (c and d) and AG ghrelin suppression (e and f) vs android body fat at 12 and 24 months, respectively. Δ = change between 24 month – baseline. Ghrelin suppression defined as postprandial – fasting.

Figure 3

Correlation between the change in fasting (a and b), postprandial (c and d) and AG ghrelin suppression (e and f) vs the change in GLP-1 at 12 and 24 months, respectively. Δ = change between 24 month – baseline. Ghrelin suppression defined as postprandial – fasting. GLP-1 stimulation defined as postprandial – fasting.