Incretins, diabetes, and bariatric surgery: a review
Rachel Fetner, M.D.
, James McGinty, M.D.
, Colleen Russell, Ph.D.
F. Xavier Pi-Sunyer, M.D., M.P.H.
, Blandine Laferrère, M.D.
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, St. Luke’s-Roosevelt Hospital Center, Columbia University College of
Physicians and Surgeons, New York, New York
Department of Surgery, Division of Bariatric Surgery, St. Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons,
New York, New York
Obesity Research Center, St. Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York
Manuscript received April 28, 2005; revised August 5, 2005; accepted September 2, 2005
Keywords: Incretin; Glucagon-like peptide 1; Gastric inhibitory polypeptide; Glucose-dependent insulinotropic polypeptide;
Type 2 diabetes mellitus; Bariatric surgery; Obesity
The prevalence of type 2 diabetes mellitus is increasing
rapidly in the United States, with almost 16 million adults
currently affected . Obesity is an independent risk factor
for diabetes. Among diabetic individuals, 50% are obese,
surgery (surgical weight loss) has become an effective treat-
ment for morbid obesity in those patients who have failed
medical management of their illness. Up to 30% of patients
presenting for bariatric surgery have type 2 diabetes melli-
for weight loss, the Roux-en-Y gastric bypass (GBP), results
in a percentage of excess weight loss (%EWL) of 50% to
by improving both insulin secretion and sensitivity . The
possible role of the gut hormones known as incretins in the
improvement of diabetes after bariatric surgery has been
hypothesized. The incretins, gut peptides secreted in re-
sponse to meals, enhance insulin secretion. The impaired
incretin secretion in obese type 2 diabetes mellitus is par-
In this article we review the role of incretins in insulin
secretion and in type 2 diabetes mellitus and the role of
bariatric surgery in the improvement of diabetes and the
response of incretins after surgery. As more morbidly obese
diabetic patients undergo bariatric surgery, understanding
the factors contributing to the improvement of their diabetes
becomes increasingly important.
The incretin effect, deﬁned by Creutzfeldt, describes “the
phenomenon of oral glucose eliciting a greater insulin re-
sponse than intravenous glucose, even when the same
amount of glucose is infused or an equivalent rise in gly-
several neurotransmitters and gut hormones have incretin-
like activity, evidence suggests that gastric inhibitory
polypeptide/glucose-dependent insulinotropic polypeptide
(GIP) and glucagon-like peptide 1 (GLP-1) are the domi-
nant peptides responsible for nutrient-stimulated insulin se-
A peptide of 42 amino acids belonging to the glucagon-
secretin family of peptides, GIP is secreted from K cells in
the duodenum in response to absorbable carbohydrates and
by the enzyme dipeptidyl peptidase IV (DPP-IV). The me-
tabolites of GIP are also eliminated rapidly, resulting in a
Reprint requests: Rachel Fetner, M.D., 29 Barstow Road—Suite 305,
Great Neck, NY 11021.
Surgery for Obesity and Related Diseases 1 (2005) 589 –598
1550-7289/05/$ – see front matter © 2005 American Society for Bariatric Surgery. All rights reserved.