Markers and Mechanisms of Vascular Disease in Type II Diabetes

May 21, 2014 updated by: US Department of Veterans Affairs

CSP #465D - Markers And Mechanisms of Vascular Disease in Type II Diabetes

OBJECTIVES: Vascular Disease is the leading cause of complications and death in patients with diabetes. Risk markers and underlying mechanisms have not been fully elucidated, and may differ from those in non-diabetic individuals. The unifying theme for the Program Project is that hyperglycemia and insulin resistance alter a number of biological processes which interact in vicious cycles to accelerate atherogenesis and are consequently major underlying risk factors for vascular disease. The overall objectives are to define these unique processes and to elucidate underlying biochemical, metabolic, and genetic determinants of vascular disease complications in diabetes.

RESEARCH PLAN: Over the past 4 years, we have collaborated with the DCCT/EDIC Study Group, and have made novel observations regarding vascular disease pathogenesis in Type 1 Diabetes. This work has focused our studies on specific pathogenic processes. We will now study a Type 2 Diabetes cohort from the VA Cooperative Study, "Glycemic Control and the Complications of Diabetes, Type 2", with high vascular disease event rates. These collaborations provide a unique opportunity to address the pathogenesis of accelerated atherogenesis in the two main types of diabetes, and will greatly augment the scientific knowledge that will be gained in the conduct of these world-class prospective trials.

METHODS: The Program Project has 4 projects and 3 cores. Project 1 will assess lipoproteins, glycoxidative stress, and inflammation as risk factors in studies involving Type 2 Diabetes patients and cultured cell systems. Based on preliminary data from our initial studies Type 1 patients, changes in the NMR lipoprotein subclass profile will be emphasized.

Project 2 will elucidate interactions between inflammation, modifications of lipoproteins, and autoimmunity in vascular disease risk. These novel concepts are also based upon exciting preliminary data pertaining to LDL-antibody complexes.

Project 3 will pursue interesting preliminary data and define the role of the kallikrein-kinin system in vascular disease complications, with effects on mitogenesis and matrix production.

Project 4 will assess the role of the Insulin Resistance Syndrome and novel factors secreted from adipocytes in the pathophysiology of biochemical risk factors and cardiovascular complications.

Cores include an Administrative Core, a Biostatistics and Epidemiology Core which will link with the trials data coordinating centers, and Molecular and Statistical Genetics Core. Investigators will work in close collaboration with the VA Executive Committee, Study Centers, the Hines Coordinating Center, and some of the other ancillary studies. All data analysis involving clinical outcomes will be performed at the Hines Coordinating Center.

There is true synergism among the projects at both scientific and logistical levels. The Program Project design allows for interactions among multidisciplinary investigators studying the same cohort, which will define how multiple pathological processes interact at the level of the arterial wall to promote atherosclerosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Hypothesis:

Secondary Hypotheses:

Primary Outcomes:

Study Abstract:

OBJECTIVES: Vascular Disease is the leading cause of complications and death in patients with diabetes. Risk markers and underlying mechanisms have not been fully elucidated, and may differ from those in non-diabetic individuals. The unifying theme for the Program Project is that hyperglycemia and insulin resistance alter a number of biological processes which interact in vicious cycles to accelerate atherogenesis and are consequently major underlying risk factors for vascular disease. The overall objectives are to define these unique processes and to elucidate underlying biochemical, metabolic, and genetic determinants of vascular disease complications in diabetes.

RESEARCH PLAN: Over the past 4 years, we have collaborated with the DCCT/EDIC Study Group, and have made novel observations regarding vascular disease pathogenesis in Type 1 Diabetes. This work has focused our studies on specific pathogenic processes. We will now study a Type 2 Diabetes cohort from the VA Cooperative Study, "Glycemic Control and the Complications of Diabetes, Type 2", with high vascular disease event rates. These collaborations provide a unique opportunity to address the pathogenesis of accelerated atherogenesis in the two main types of diabetes, and will greatly augment the scientific knowledge that will be gained in the conduct of these world-class prospective trials.

METHODS: The Program Project has 4 projects and 3 cores. Project 1 will assess lipoproteins, glycoxidative stress, and inflammation as risk factors in studies involving Type 2 Diabetes patients and cultured cell systems. Based on preliminary data from our initial studies Type 1 patients, changes in the NMR lipoprotein subclass profile will be emphasized.

Project 2 will elucidate interactions between inflammation, modifications of lipoproteins, and autoimmunity in vascular disease risk. These novel concepts are also based upon exciting preliminary data pertaining to LDL-antibody complexes.

Project 3 will pursue interesting preliminary data and define the role of the kallikrein-kinin system in vascular disease complications, with effects on mitogenesis and matrix production.

Project 4 will assess the role of the Insulin Resistance Syndrome and novel factors secreted from adipocytes in the pathophysiology of biochemical risk factors and cardiovascular complications.

Cores include an Administrative Core, a Biostatistics and Epidemiology Core which will link with the trials data coordinating centers, and Molecular and Statistical Genetics Core. Investigators will work in close collaboration with the VA Executive Committee, Study Centers, the Hines Coordinating Center, and some of the other ancillary studies. All data analysis involving clinical outcomes will be performed at the Hines Coordinating Center.

There is true synergism among the projects at both scientific and logistical levels. The Program Project design allows for interactions among multidisciplinary investigators studying the same cohort, which will define how multiple pathological processes interact at the level of the arterial wall to promote atherosclerosis.

Main Manuscript:

There is no independent data for this study, it was part of a larger study. Therefore there will be no results for this record/study.

Study Type

Observational

Enrollment (Actual)

298

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00921
        • VA Medical Center, San Juan
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85012
        • Carl T. Hayden VA Medical Center
      • Tucson, Arizona, United States, 85723
        • Southern Arizona VA Health Care System, Tucson
    • California
      • Fresno, California, United States, 93703
        • VA Central California Health Care System, Fresno
      • Long Beach, California, United States, 90822
        • VA Medical Center, Long Beach
      • San Diego, California, United States, 92161
        • VA San Diego Healthcare System, San Diego
    • Florida
      • Miami, Florida, United States, 33125
        • Miami VA Healthcare System, Miami, FL
    • Illinois
      • Hines, Illinois, United States, 60141-5000
        • Edward Hines, Jr. VA Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
        • Richard Roudebush VA Medical Center, Indianapolis
    • Kentucky
      • Lexington, Kentucky, United States, 40502
        • VA Medical Center, Lexington
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • VA Medical Center, Minneapolis
    • Nebraska
      • Omaha, Nebraska, United States, 68105-1873
        • VA Medical Center, Omaha
    • New Jersey
      • East Orange, New Jersey, United States, 07018
        • VA New Jersey Health Care System, East Orange
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Health Care System
    • Texas
      • Houston, Texas, United States, 77030
        • Michael E. DeBakey VA Medical Center (152)
      • San Antonio, Texas, United States, 78229
        • VA South Texas Health Care System, San Antonio
    • Virginia
      • Salem, Virginia, United States, 24153
        • VA Medical Center, Salem VA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2".

Description

Inclusion Criteria:

Patients with type 2 DM who are no longer responsive to maximum dose of one or more oral agents

Exclusion Criteria:

Patients that did not participate in the VADT.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group 1
Patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2".
Drug: Rosiglitazone
ROSIGLITAZONE (roe si GLI ta zone) helps to treat type 2 diabetes. It helps to control blood sugar. Treatment is combined with diet and exercise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary outcome measure is to define these unique processes and to elucidate underlying biochemical, metabolic, and genetic determinants of vascular disease complications in diabetes.
Time Frame: 2, 4, and 6 years.
2, 4, and 6 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Department of Veterans Affairs

Collaborators

American Diabetes Association

Investigators

  • Study Chair: Carlos Abraira, MD, Miami VA Healthcare System, Miami, FL

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

November 17, 2005

First Submitted That Met QC Criteria

November 17, 2005

First Posted (Estimate)

November 21, 2005

Study Record Updates

Last Update Posted (Estimate)

May 23, 2014

Last Update Submitted That Met QC Criteria

May 21, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 465D

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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