The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Registration Number
- NCT00179400
- Lead Sponsor
- Albert Einstein College of Medicine
- Brief Summary
The purpose of this study is to investigate the acute effects of the thiazolidinedione agent pioglitazone (which has combined PPAR alpha and gamma stimulation) on insulin's ability to suppress glucose production, stimulated glucose uptake, and impact a number of other metabolically important endpoints, including production of adiponectin (a protein hormone which regulates sugar levels and fatty acid breakdown) in subjects with type 2 diabetes.
- Detailed Description
Participants in this study were given a supply of either pioglitazone (a medication used to treat diabetes) or matched placebo for a duration of 10 days or 21 days. Changes to the body's response to insulin in the liver and in peripheral tissues (eg, muscle and fat) will be measured using a procedure called a pancreatic clamp. During the clamp procedure, glucose (a sugar) and insulin were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Small amounts of muscle and fat tissue were also taken during this study to measure changes in gene expression after taking the medication/placebo.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
• Individuals with Type 2 Diabetes
- Individuals with bleeding disorders including gastrointestinal reflux disease (GERD), peptic ulcer disease (PUD), any gastrointestinal (GI) bleeding
- High blood pressure
- History of Coronary Artery Disease or chest pain on exertion
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Pioglitazone Pioglitazone Participants received Pioglitazone 45 mg via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism. Pioglitazone Pancreatic Clamp Study Participants received Pioglitazone 45 mg via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism. Placebo Placebo Participants received matched placebo via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism. Placebo Pancreatic Clamp Study Participants received matched placebo via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are related to glucose metabolism.
- Primary Outcome Measures
Name Time Method Endogenous Glucose Production (EGP) Up to 6 hours EGP (a measure of the body's production of sugar) was measured by using a 6-hour stepped pancreatic clamp procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days), by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). The relevant data at the end of each last 60 minute bin of each run was reported for each of the four groups up to 6 hours. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
Glucose Rates of Disappearance (Rd) Up to 6 hours Glucose rates of disappearance were measured using a stepped pancreatic clamp study procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days) by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). For purposes of this study, the most relevant data for the final hour is summarized within each study Pioglitazone and Placebo study arm/group, respectively. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
- Secondary Outcome Measures
Name Time Method Gene Expression in Both Whole Fat Tissue and Isolated Macrophages Outcome was compared prior to and post 10-day or 21-day administration of either placebo or Pioglitazone Gene expression of inflammatory markers in both whole fat tissue and isolated macrophages were studied by quantitative, real-time reverse transcriptase polymerase chain reaction (RT-PCR) in placebo and Pioglitazone groups of either 10- or 21-day study. The reporting data was calculated as the ratio between the target genes and housekeeping genes in either the 10- or 21-day study.
Effects of Pioglitazone on Adipose Tissue Percentage of Macrophage Content Assessed at day 1 prior to the intervention and on day 10 or 21 following the intervention, day 10 or 21 following the intervention reported Adipose tissue biopsy was performed on day one or on the last day (10th or 21st day) for the corresponding Pioglitazone and placebo interventions. Macrophages were stained with immunofluorescence antibody after isolation from adipose tissue and processed. The percentage of macrophage content in stromal vascular fraction cells (SVF) analyzed by Fluorescence-activated cell sorter analysis (FACS) was determined. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).
Adipose Tissue Percentage of Macrophage Content Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration Adipose tissue percentage of macrophage content was analyzed by Immuno-fluorescence staining (iNOS+ and CD68+). Both the immuno-fluorescence stained macrophages and all other stained cells will be counted after staining. The percentage of macrophage content will be calculated as the the ratio between the number of macrophage and all other cells.
Adipose Tissue Regulatory T Lymphocyte Content Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration Adipose tissue T lymphocyte content (%) was analyzed by Immunohistochemistry (IHC) staining with Treg-specific marker FOXP3
Both the IHC FOXP3 stained T lymphocyte and all other stained cells will be counted after staining. The percentage of T lymphocyte content will be calculated as the the ratio between the number of T lymphocyte and all other cells.
Trial Locations
- Locations (1)
Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States