Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance

Jorgensen NB, Jacobsen SH, Dirksen C, Bojsen-Moller KN, Naver L, Hvolris L, Clausen TR, Wulff BS, Worm D, Hansen DL, Madsbad S, Holst JJ. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance. Am J Physiol Endocrinol Metab 303: E122-E131, 2012. First published April 24, 2012; doi: 10.1152/ajpendo.00073.2012.-Our aim was to study the potential mechanisms responsible for the improvement in glucose control in Type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Thirteen obese subjects with T2D and twelve matched subjects with normal glucose tolerance (NGT) were examined during a liquid meal before (Pre), 1 wk, 3 mo, and 1 yr after RYGB. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent-insulinotropic polypeptide (GIP), and glucagon concentrations were measured. Insulin resistance (HOMA-IR), beta-cell glucose sensitivity (beta-GS), and disposition index (D beta-GS: beta-GS x 1/HOMA-IR) were calculated. Within the first week after RYGB, fasting glucose [T2D Pre: 8.8 +/- 2.3, 1 wk: 7.0 +/- 1.2 (P < 0.001)], and insulin concentrations decreased significantly in both groups. At 129 min, glucose concentrations decreased in T2D [Pre: 11.4 +/- 3, 1 wk: 8.2 +/- 2 (P = 0.003)] but not in NGT. HOMA-IR decreased by 50% in both groups. beta-GS increased in T2D [Pre: 1.03 +/- 0.49, 1 wk: 1.70 +/- 1.2, (P = 0.012)] but did not change in NGT. The increase in DI beta-GS was 3-fold in T2D and 1.5-fold in NGT. After RYGB, glucagon secretion was increased in response to the meal. GIP secretion was unchanged, while GLP-1 secretion increased more than 10-fold in both groups. The changes induced by RYGB were sustained or further enhanced 3 mo and 1 yr after surgery. Improvement in glycemic control in T2D after RYGB occurs within days after surgery and is associated with increased insulin sensitivity and improved beta-cell function, the latter of which may be explained by dramatic increases in GLP-1 secretion.