Relationship Between Changes in Gut Hormones After Gastric Bypass and Gastric Banding and Improvements in Diabetes

Many diabetic patients who have Roux-en-Y gastric bypass (RYGB) have rapid improvements in
their blood sugars within days of their surgery, even before they have lost much weight. It
typically takes much longer for these improvements to occur after adjustable gastric banding
(AGB), despite an equally low caloric intake. Changes in levels of hormones released by the
small intestine as a consequence of the particular type of surgery may be an important
factor in the rapid improvement of blood sugars. One of these hormones, glucagon-like
peptide-1 (GLP-1), has an important effect on insulin secretion from the pancreas. This
study seeks to determine whether changes in GLP-1 are responsible for the improvement in
blood sugar after certain types of weight loss surgeries. In order to meet inclusion
criteria, participants must have type 2 diabetes for less than 10 years and be approved by
insurance to undergo RYGB or AGB at the Hospital of the University of Pennsylvania or Penn
Presbyterian Medical Center. We will obtain several measurements of GLP-1 and other hormones
that affect glucose levels during the three study visits: 1) Visit 1 (2-3 weeks before
surgery); 2) Visit 2 (after 10% of body weight is lost); and 3) Visit 3 (5-10 days after
Visit 2). To see if the improvement in blood sugar after surgery is due to changes in GLP-1,
we will block its effect on insulin release by giving either salt water or a medication that
blocks the activity of GLP-1 during the two visits that take place after surgery (Visits 2
and 3). Each visit will last for 4-6 hours and participants will be compensated for their
time.

Inclusion Criteria:

- Male and female participants age 18 years or older with a body mass index greater
than >35 kg/m2 but less than <60 kg/m2 who undergo gastric bypass or gastric banding
at the University of Pennsylvania.

- Type 2 diabetes (defined as a pre-existing diagnosis, the use of oral antidiabetic
medications or insulin, or a fasting plasma glucose greater than or equal to > 126
mg/dl and confirmed by a oral glucose tolerance test)

- Ability to provide written informed consent

Exclusion Criteria:

- A diagnosis of type 1 diabetes

- Daily insulin requirement exceeding 1 unit/kg/d

- Poor preoperative glycemic control, as indicated by an HbA1c greater than 10.0%

- Duration of diabetes greater than> 10 years

- Pregnant women (or those who intend to become pregnant during the study period)

- Women who are currently breastfeeding

- Participants with moderate anemia (hemoglobin less than< 12 g/dl for men and less
than< 11 g/dl for women)

- Use of medications known to affect weight, including chronic oral or inhaled
glucocorticoid use and the use of certain psychiatric medications (olanzepine,
risperidone, and lithium)

- history of any major active rheumatologic, pulmonary, dermatologic disease, or
inflammatory conditions

- oral history of positive HIV status

- any major surgery in the past 3 months

- regular use of alcoholic beverages (greater than 7 drinks/week)

- prior reaction to human albumin