Impact of Gastric Bypass Surgery on Gut Hormones and Glucose Homeostasis in Type 2 Diabetes
Erik Na slund
1
John G. Kral
0
0
Department of Surgery, State University of New York, Downstate Medical Center, Brooklyn, New York. Division of Surgery, Karolinska Institutet, Danderyd Hospital
,
SE-182 88 Stockholm
,
Sweden
1
Division of Surgery, Karolinska Institutet Danderyd Hospital
,
Stockholm
,
Sweden; and the
Gastric bypass surgery (GBP) for obesity, by constructing an isolated 30-ml proximal gastric pouch connected to a 75-cm limb of proximal jejunum, bypassing >90% of the stomach, the pylorus, and the duodenum, cures type 2 diabetes in >80% of cases. We review alterations in gastrointestinal peptide release after GBP that affect glucose disposal. We focus on ghrelin and the incretins glucosedependent insulinotropic polypeptide, glucagon-like peptide 1, and peptide YY as the most likely candidates for increasing insulin sensitivity after these operations, even before substantial weight loss has occurred. Although we have limited our review to only four gastrointestinal peptides, others may be involved, as are adipocyte-derived molecules such as leptin and adiponectin, and substrate receptor interactions in target tissues including the brain. Diabetes 55 (Suppl. 2):S92-S97, 2006 tive and purely restrictive being least effective (4). Many surgeons have observed that patients with type 2 diabetes exhibit improved glycemic control very early after antiobesity surgery, even before any weight loss has occurred. This seemed to be more pronounced in patients undergoing diversionary rather than purely restrictive operations (5,6), leading to the speculation that the effect is due to alterations in the release of gastrointestinal (GI) peptides that influence glycemic control. The aim of this article is to explore the phenomenon of improved glycemic control, focusing on GBP, the most commonly performed surgical procedure with the richest literature documenting postoperative resolution of type 2 diabetes. We describe the different anti-obesity procedures, followed by the changes in postoperative GI peptide release, concluding by discussing how these peptides may influence the changes in food intake and glycemic control seen after anti-obesity surgery.
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Taccompanied by an explosion in the prevalence
he increasing prevalence of obesity worldwide is
of type 2 diabetes (1,2); 60% of all cases of
diabetes are attributable to obesity. In light of
this, it has been proposed that obesity has become to
diabetes what tobacco is to lung cancer (2).
Surgeons have for some time been able to contribute to
the understanding of mechanisms involved in diabetes by
studying human tissue (3). Today, surgery is the most
effective treatment for obesity and has been proven to
improve quality of life, glycemic control, triglyceride
levels, and blood pressure with long-term follow-up (4). The
surgical procedures in use today can be divided into three
different categories: purely restrictive, such as adjustable
gastric banding (AGB) (Fig. 1); combined
restrictive/malabsorptive, or diversionary procedures, such as gastric
bypass (GBP) (Fig. 2); and mainly malabsorptive,
exemplified by biliopancreatic diversion (BPD) (Fig. 3) with or
without duodenal switch. These procedures achieve
different long-term results with regard to resolving type 2
diabetes, with malabsorptive procedures being most
effec
EFFECT OF GASTRIC BYPASS ON GLUCOSE
That GBP has a long-term positive effect on both the
resolution of type 2 diabetes and in preventing new cases
with type 2 diabetes is clear (4,6). In a longitudinal study of
obese subjects with impaired glucose tolerance followed
for 5 years, anti-obesity surgery lowered the rate of
progression to type 2 diabetes by 30-fold (7). Today, it is
also clear that GBP has an early and very profound
positive effect on glucose homeostasis. Several studies
have examined the effect of GBP on glucose homeostasis
3 4 weeks after GBP; mean BMI was not significantly
changed, but fasting plasma glucose and insulin were
significantly reduced. Insulin resistance improved after 4
weeks and continued to improve over the 6 months of
follow-up (8,9). Thus, it is now established that GBP
significantly improves type 2 diabetes over the short and long term.
DIFFERENT ANTI-OBESITY OPERATIONS
Purely restrictive surgery. Purely restrictive bariatric
operations cause weight loss by limiting the capacity of
the stomach to accommodate food and constricting the
flow of ingested nutrients. Today, two such procedures are
performed: vertical banded gastroplasty (VBG) and AGB.
VBG entails a partitioning staple line that extends upward
from a circular stapled hole in the stomach (to exclude the
easily dilatable fundus). A synthetic band is used to
reinforce the stoma (Fig. 1A), which has a diameter of 1
cm. The pouch commonly measures 30 ml. Although VBG
effectively limits the amount of food that can be consumed
at one sitting and causes 30 50% reduction of excess body
weight within the first 12 years, long-term results from
the U.S. are (...truncated)