Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes

Abstract

Objective: Limited data on patients undergoing Roux-en-Y gastric bypass surgery (RY-GBP) suggest that an improvement in insulin secretion after surgery occurs rapidly and thus may not be wholly accounted for by weight loss. We hypothesized that in obese patients with type 2 diabetes the impaired levels and effect of incretins changed as a consequence of RY-GBP.

Research design and methods: Incretin (gastric inhibitory peptide [GIP] and glucagon-like peptide-1 [GLP-1]) levels and their effect on insulin secretion were measured before and 1 month after RY-GBP in eight obese women with type 2 diabetes and in seven obese nondiabetic control subjects. The incretin effect was measured as the difference in insulin secretion (area under the curve [AUC]) in response to an oral glucose tolerance test (OGTT) and to an isoglycemic intravenous glucose test.

Results: Fasting and stimulated levels of GLP-1 and GIP were not different between control subjects and patients with type 2 diabetes before the surgery. One month after RY-GBP, body weight decreased by 9.2 +/- 7.0 kg, oral glucose-stimulated GLP-1 (AUC) and GIP peak levels increased significantly by 24.3 +/- 7.9 pmol x l(-1) x min(-1) (P < 0.0001) and 131 +/- 85 pg/ml (P = 0.007), respectively. The blunted incretin effect markedly increased from 7.6 +/- 28.7 to 42.5 +/- 11.3 (P = 0.005) after RY-GBP, at which it time was not different from that for the control subjects (53.6 +/- 23.5%, P = 0.284).

Conclusions: These data suggest that early after RY-GBP, greater GLP-1 and GIP release could be a potential mediator of improved insulin secretion.

Figure 1

Total GLP-1 (A), GIP (B), and active GLP-1 (C) levels during OGTTs in patients before (♦) and after (■) RY-GBP (A) and in control subjects (▲) and incretin effect on insulin secretion (D) in control subjects (□), patients before RY-GBP (), and patients after RY-GBP (■). The incretin effect was calculated by comparing the insulin response to oral and matched IV glucose loads. Data are means±SEM. *P<0.05 compared with patients before RY-GBP. #P < 0.05 compared with control subjects.

Figure 2

Glucose (A and D), insulin (B and E), and C-peptide (C and F) concentrations during OGTTs (♦) and IsoG IVGTs (■) before (A–C) and after (D–F) RY-GBP. Data are means ± SEM. *P < 0.05, significant difference between OGTT and IsoG IVGT values within each condition (before or after RY-GBP).