Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes Mellitus, Gastric Bypass Surgery, Exendin9
Brief summary
Longitudinal study of beta cell function up to 2 years after GBP surgery. Evaluation of the role of endogenous glucagon-like peptide-1 (GLP-1).
Detailed description
The increased prevalence of obesity and type 2 diabetes (T2DM) has resulted in a surge in the number of patients seeking surgical weight loss. Gastric bypass surgery (GBP) results in 30-40% body weight loss with resolution of T2DM in 40-80% of cases. The mechanisms by which T2DM improves after GBP are unclear. Glycemic control occurs long before significant weight loss, suggesting that the nature of the procedure, rather than the weight loss, is responsible for the T2DM improvement. Recent data have singled out the role of the gut hormones known as incretins in diabetes improvement after GBP. The current proposal will study 1) whether the short and long term change in the gut hormone incretins after GBP results in improved insulin secretion in response to the administration of oral and IV glucose, in patients with diabetes undergoing GBP surgery; 2) the factors responsible for diabetes remission - or lack of - after GBP. The investigators wish to apply our finding to define better surgical outcome on diabetes.
Interventions
DRUGExendin9
Dosed at 600 pmol/kg/min for 210 minutes.
Sponsors
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Blandine Laferrere
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients with a wide range of T2DM (duration, treatment modalities and control, in or not in remission) and scheduled for GBP surgery * Blood pressure is under at least moderate control \<160/100 mmHg * Patients can be on dyslipidemia medications but need fasting triglyceride \< 600 mg/dl * Patients without recent (last 6 months) history of cardiovascular disease (CVD) * BMI \> 35 and \< 55 kg/m2 prior to GBP surgery
Exclusion criteria
* Active cancer * Unstable angina * Recent stroke * Current therapy that may affect glucose metabolism such as glucocorticoids, HIV medications, etc * Active infection * Kidney failure * Severe liver dysfunction * Severe respiratory or cardiac failure * History of allergic reaction to exendin 9-39 * History of pancreatitis, history of cholelithiasis, history of alcoholism * Presence of high triglyceride levels (\>600 ng/dl) * Pregnancy (a pregnancy test will be done prior to enrollment and prior to each procedure in all premenopausal women)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Beta Cell Sensitivity (BCS) | at 2 years post GBP surgery | Oral glucose tolerance test (OGTT) will be used to calculate BCS Graded glucose infusion with arginine (GGI) will be used to calculate BCS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Secretion Rate (ISR) after OGTT | 2 years post GBP surgery | An oral glucose tolerance test (OGTT) will be used to estimate ISR in subjects before and up to 2 years after GBP |
| Insulin Secretion Rate (ISR) after GGI | 2 years post GBP surgery | A graded glucose infusion with arginine (GGI) will be used to estimate ISR in subjects before and up to 2 years after GBP |
| Maximal Beta Cell Function | 2 years post GBP surgery | The effect of a graded glucose infusion with arginine (GGI) on insulin secretion rate (ISR) will be measured in subjects before and up to 2 years after GBP |
Countries
United States
Outcome results
None listed