Effects of Pramlintide on Endogenous Production of Very-low-density-lipoprotein (VLDL)-Triglyceride and Glucose in the Post Prandial State in T2DM

Study Overview
=================
Brief Summary
-----------------
Diabetes affects almost 21 million people in the United States. In this study we will test a drug called Pramlintide(Symlin), and see how it works to lower blood sugar and fat levels after a meal. Lowering high sugar levels and fat levels after a meal is very important in the prevention of the problems that persons with type 2 diabetes often encounter. Hypothesis is that Pramlintide will lower blood sugar and fat levels after a meal.

Detailed Description
-----------------
A well recognized and troublesome feature of diabetes management is the exacerbated post prandial glucose elevations following a typical high fat meal. To date the mechanisms driving this increased post prandial glycemia are unclear. Pramlintide is believed to affect intermediary metabolism as well as nutrient absorption. The relative contributions from altered absorption and metabolism to the observed post prandial reductions in plasma glucose and TG concentrations remain uncertain, however. Combinations of radioactive and stable isotope labeling techniques are able to quantify the relevant fluxes of glucose and lipids in vivo in humans and are therefore able to provide quantitative answers to these questions. Aims: To determine the effects of Pramlintide on reducing endogenous production of very-low-density-lipoprotein (VLDL)-triglycerides(TG) following a high fat breakfast, lunch and dinner in patients with type 2 diabetes mellitus (T2DM). A triple isotope approach will be used to determine rate of appearance of (VLDL)-triglycerides following breakfast, lunch and dinner. To compare the relative roles of slowed glucose absorption and reduced endogenous glucose production (glucagonstatic mechanism) in the glucose-lowering effects of Pramlintide in the post prandial state in patients with T2DM.

Official Title
-----------------
Effects of Pramlintide on Endogenous Production of VLDL-Triglyceride and Glucose in the Post Prandial State in Type 2 Diabetes Mellitus

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Pramlintide acetate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 DM study participants will be C-Peptide positive (levels > 0.3 nmol/L) Receiving insulin, metformin and/or sulfonylurea/glitinide. Maintained on stable anti-hypertensive medication. BMI < 52 kg/m2. T2DM for at least 3 months with HBA1C under 10%. Exclusion Criteria: Receiving TZDs, exenatide, sitagliptin or pramlintide therapy. Receiving medications known to impair gastric emptying, intestinal motility, glucagon release or corticosteroids. Triglyceride levels > 400 mg/dl. BMI > 52 kg/m2.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 2<br>Type 2 diabetes patients will receive placebo with 3 meals in experimental period. | Drug: Placebo<br>* 120 micrograms given subcutaneously before each meal x 3.<br>|
| Experimental: 1<br>Type 2 Diabetes patient will receive Pramlintide with 3 meals in experimental period. | Drug: Pramlintide acetate<br>* 120 micrograms given subcutaneously before each meal X 3.<br>* Other names: Symlin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endogenous glucose production |  | 18 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endogenous VLDL-Triglyceride production |  | 18 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
triglycerides, endogenous, glucose, production