Markers and Mechanisms of Vascular Disease in Type II Diabetes
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Arizona
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Phoenix、Arizona、アメリカ、85012
- Carl T. Hayden VA Medical Center
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Tucson、Arizona、アメリカ、85723
- Southern Arizona VA Health Care System, Tucson
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California
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Fresno、California、アメリカ、93703
- VA Central California Health Care System, Fresno
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Long Beach、California、アメリカ、90822
- VA Medical Center, Long Beach
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San Diego、California、アメリカ、92161
- VA San Diego Healthcare System, San Diego
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Florida
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Miami、Florida、アメリカ、33125
- Miami VA Healthcare System, Miami, FL
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Illinois
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Hines、Illinois、アメリカ、60141-5000
- Edward Hines, Jr. VA Hospital
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Indiana
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Indianapolis、Indiana、アメリカ、46202-2884
- Richard Roudebush VA Medical Center, Indianapolis
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Kentucky
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Lexington、Kentucky、アメリカ、40502
- VA Medical Center, Lexington
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Minnesota
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Minneapolis、Minnesota、アメリカ、55417
- VA Medical Center, Minneapolis
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Nebraska
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Omaha、Nebraska、アメリカ、68105-1873
- VA Medical Center, Omaha
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New Jersey
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East Orange、New Jersey、アメリカ、07018
- VA New Jersey Health Care System, East Orange
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15240
- VA Pittsburgh Health Care System
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Texas
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Houston、Texas、アメリカ、77030
- Michael E. DeBakey VA Medical Center (152)
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San Antonio、Texas、アメリカ、78229
- VA South Texas Health Care System, San Antonio
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Virginia
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Salem、Virginia、アメリカ、24153
- VA Medical Center, Salem VA
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San Juan、プエルトリコ、00921
- VA Medical Center, San Juan
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
Group 1
Patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2".
|
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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
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.
時間枠：2, 4, and 6 years.
|
2, 4, and 6 years.
|
協力者と研究者
捜査官
- スタディチェア：Carlos Abraira, MD、Miami VA Healthcare System, Miami, FL
出版物と役立つリンク
一般刊行物
- Lopes-Virella MF, Hunt KJ, Baker NL, Virella G, Moritz T; VADT Investigators. The levels of MDA-LDL in circulating immune complexes predict myocardial infarction in the VADT study. Atherosclerosis. 2012 Oct;224(2):526-31. doi: 10.1016/j.atherosclerosis.2012.08.006. Epub 2012 Aug 21.
- Bhensdadia NM, Hunt KJ, Lopes-Virella MF, Michael Tucker J, Mataria MR, Alge JL, Neely BA, Janech MG, Arthur JM; Veterans Affairs Diabetes Trial (VADT) study group. Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes. Kidney Int. 2013 Jun;83(6):1136-43. doi: 10.1038/ki.2013.57. Epub 2013 Mar 27.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。