This study will evaluate whether bile acids are able to increase insulin sensitivity and enhance glycemic control in T2DM patients, as well as exploring the mechanisms that enhance glycemic control. These observations will provide the preliminary data for proposing future therapeutic as well as further mechanistic studies of the role of bile acids in the control of glycemia in T2DM.
Background: Intra-jejunal administration of bile acids improves insulin sensitivity. Hypothesis: The bile acid, ursodeoxycholic acid (UDCA) in delayed (ileocolonic)-release formulation, stimulates bile acid membrane receptor (TGR-5) and farnesol X (FXR) receptors in the ileum and colon, increasing the secretion of Fibroblast growth factor 19 (FGF-19), GLP-1, oxyntomodulin (OXM), and Peptide (PYY3-36), improving insulin sensitivity and inducing weight loss. Aim: To study the effect of an ileocolonic formulation of UDCA on insulin sensitivity, postprandial plasma glycemia and incretin levels, gastric emptying and body weight in overweight or obese type 2 diabetic subjects on monotherapy with metformin. Study design: This is a single center, placebo-controlled, parallel group, single dose randomized controlled trial to study the effect of delayed (ileocolonic)-release UDCA 600 mg twice daily on insulin sensitivity, gastric emptying of liquids and solids (measured by scintigraphy)and weight loss in overweight or obese type 2 diabetic subjects. Participants will be receiving monotherapy with metformin. Blood samples will be collected at defined times to measure glycemia and the incretin (GLP-1, OXM, PYY3-36) fasting levels and responses to the meal. Anticipated Results: In comparison with placebo, UDCA will increase insulin sensitivity, enhance glycemic control, increase postprandial incretins, and delay gastric emptying (GE) of liquids. Significance: This study will prove that ileocolonic-release UDCA enhances glycemic control in T2DM patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
24
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Change in Area Above Basal (AAB) for Glucose
Mixed meal glucose results are used to calculate the area above basal (AAB) for glucose. The glycemic index of a food is defined as the incremental area under the two-hour blood glucose response curve (AUC) following an overnight fast and ingestion of a food with a certain quantity of available carbohydrate (usually 50 g).
Time frame: baseline, post-treatment approximately 14 - 17 days
Change in Fasting Glucose
Serum glucose measurements taken after 10 hours of fasting.
Time frame: baseline, post-treatment approximately 14 - 17 days
Change in Insulin Sensitivity
Insulin sensitivity will be calculated by the oral minimal model.
Time frame: baseline, post-treatment approximately 14 - 17 days
Gastric Emptying of Liquids (T1/2)
The time for half of the ingested liquids to leave the stomach. Following a meal with milk labeled with indium In111 diethylenetriaminepentaacetate (0.1 mCi), gastric emptying of liquids was assessed with scintigraphy imaging.
Time frame: post-treatment, approximately 14-17 days
Gastric Emptying of Solids (T1/2)
The time for half of the ingested solids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi) served with 50g of Canadian bacon and one slice of bread gastric emptying of solids was assessed with scintigraphy imaging.
Time frame: post-treatment, approximately 14-17 days
Change in Weight
Change in subject's weight, in kilograms
Time frame: baseline, post-treatment approximately 14 - 17 days
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Change in Body Mass Index
Change in subjects BMI, in kilograms per meter squared.
Time frame: baseline, post-treatment approximately 14 - 17 days
Change in FGF-19
Change in fasting fibroblast growth factor (FGF)-19 expression.
Time frame: baseline, post-treatment approximately 14 - 17 days