Non-traditional Cardiovascular Risk Factors and Atherosclerosis in Type 2 Diabetes

NCT00256607 | Completed DMC

• 1 other identifier: 465A
• Study Type: observational
• Target: 301
• Locations: 1 country
• Sites: 7

Brief Summary

A predominant consequence of diabetes mellitus (DM) type 2 is accelerated development of atherosclerosis related conditions. Conventional cardiovascular risk factors only explain a portion of the excess risk for atherosclerosis in this population. In vitro, animal and epidemiologic studies have suggested that a variety of "novel" cardiovascular risk factors (CVRF), including triglyceride-rich lipoproteins (TGRL), small dense low density lipoprotein (D-LDL) subfractions, oxidative stress, and advanced glycation endproduct (AGE) formation may contribute to the development of atherosclerosis. These risk factors may also induce endothelial cell activation/injury or local or systemic inflammation that cause elevations in plasma levels of additional novel risk factors, such as soluble adhesion molecules, plasminogen activator inhibitor-1 (PAI-1), fibrinogen and C-reactive protein (CRP). Many of these risk factors are increased in DM type 2, presumably as a consequence of hyperglycemia and insulin resistance. However, no studies have evaluated the singular or synergistic relationship of these novel (CVRF) to measures of atherosclerosis as well as to the development of clinical macrovascular events in individuals with diabetes. If, as we suspect, these novel CVRF are related to development of atherosclerosis and macrovascular disease, it will be critical for the future design of prevention strategies to know whether intensive glucose lowering significantly reduces the levels of these novel CVRF. Furthermore, it would be important to explore whether the relationship of the above novel risk factors to atherosclerosis and development of clinical events is attenuated in those individuals receiving glucose lowering therapy. Alternatively, if glucose lowering has no effect (or a negative effect), on relevant novel CVRF, this could potentially explain the limited success of intensive glucose lowering to reduce macrovascular events in several prior trials. The investigator proposes to take advantage of the study population and framework of the recently approved VA Cooperative Study of "Glycemic Control and Complications in Diabetes Mellitus Type 2" to address these issues in an efficient and cost-effective manner.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 1) Determine the cross-sectional relationship between baseline levels of novel CVRF and the

  3 to 5 years

Study Arms (1)

coronary artery calcium (CAC)

Cohort from the VADT study, had baseline coronary atherosclerosis assessed by coronary artery calcium (CAC) measured by computed tomography. Participants were followed over the 7.5-year study for development of cardiovascular endpoints.

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This observational study of patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2@

You may qualify if:

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

You may not qualify if:

• Patients that have not participated in the VADT.

Sponsors & Collaborators

• US Department of Veterans Affairs: lead

Study Sites (7)

Carl T. Hayden VA Medical Center

Phoenix, Arizona, 85012, United States

Location

Southern Arizona VA Health Care System, Tucson

Tucson, Arizona, 85723, United States

Location

VA Medical Center, Long Beach

Long Beach, California, 90822, United States

Location

VA San Diego Healthcare System, San Diego

San Diego, California, 92161, United States

Location

Miami VA Healthcare System, Miami, FL

Miami, Florida, 33125, United States

Location

Edward Hines, Jr. VA Hospital

Hines, Illinois, 60141-5000, United States

Location

VA Pittsburgh Health Care System

Pittsburgh, Pennsylvania, 15240, United States

Location

Related Publications (9)

• Reaven PD, Moritz TE, Schwenke DC, Anderson RJ, Criqui M, Detrano R, Emanuele N, Kayshap M, Marks J, Mudaliar S, Harsha Rao R, Shah JH, Goldman S, Reda DJ, McCarren M, Abraira C, Duckworth W; Veterans Affairs Diabetes Trial. Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans affairs diabetes trial participants with lower calcified coronary atherosclerosis. Diabetes. 2009 Nov;58(11):2642-8. doi: 10.2337/db09-0618. Epub 2009 Aug 3.

  PMID: 19651816 RESULT

• Reaven PD, Emanuele N, Moritz T, Klein R, Davis M, Glander K, Duckworth W, Abraira C; Veterans Affairs Diabetes Trial. Proliferative diabetic retinopathy in type 2 diabetes is related to coronary artery calcium in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2008 May;31(5):952-7. doi: 10.2337/dc07-1926. Epub 2008 Mar 3.

  PMID: 18316393 RESULT

• Reaven PD, Sacks J; Investigators for the VADT. Coronary artery and abdominal aortic calcification are associated with cardiovascular disease in type 2 diabetes. Diabetologia. 2005 Feb;48(2):379-85. doi: 10.1007/s00125-004-1640-z. Epub 2005 Feb 2.

  PMID: 15688207 RESULT

• Reaven PD, Sacks J; Investigators for the Veterans Affairs Cooperative Study of Glycemic Control and Complications in Diabetes Mellitus Type 2. Reduced coronary artery and abdominal aortic calcification in Hispanics with type 2 diabetes. Diabetes Care. 2004 May;27(5):1115-20. doi: 10.2337/diacare.27.5.1115.

  PMID: 15111530 RESULT

• Saremi A, Allison M, Ditomasso D, Ge L, Anderson R, Moritz TE, Duckworth W, Abraira C, Reaven PD; VADT. Preliminary report: hepatic fat and inflammation in type 2 diabetes mellitus. Metabolism. 2010 Mar;59(3):430-2. doi: 10.1016/j.metabol.2009.07.041. Epub 2009 Oct 21.

  PMID: 19850309 RESULT

• Saremi A, Moritz TE, Anderson RJ, Abraira C, Duckworth WC, Reaven PD; Veterans Affairs Diabetes Trial (VADT). Rates and determinants of coronary and abdominal aortic artery calcium progression in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2010 Dec;33(12):2642-7. doi: 10.2337/dc10-1388. Epub 2010 Aug 31.

  PMID: 20807873 RESULT

• Saremi A, Anderson RJ, Luo P, Moritz TE, Schwenke DC, Allison M, Reaven PD; VADT. Association between IL-6 and the extent of coronary atherosclerosis in the veterans affairs diabetes trial (VADT). Atherosclerosis. 2009 Apr;203(2):610-4. doi: 10.1016/j.atherosclerosis.2008.07.031. Epub 2008 Aug 5.

  PMID: 18804762 RESULT

• Saremi A, Bahn G, Reaven PD; VADT Investigators. Progression of vascular calcification is increased with statin use in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2012 Nov;35(11):2390-2. doi: 10.2337/dc12-0464. Epub 2012 Aug 8.

  PMID: 22875226 RESULT

• Koska J, Saremi A, Bahn G, Yamashita S, Reaven PD; Veterans Affairs Diabetes Trial Investigators. The effect of intensive glucose lowering on lipoprotein particle profiles and inflammatory markers in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2013 Aug;36(8):2408-14. doi: 10.2337/dc12-2082. Epub 2013 Mar 27.

  PMID: 23536583 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Carlos Abraira, MD

  Miami VA Healthcare System, Miami, FL

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2005
• First Posted: November 21, 2005
• Study Start: June 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: June 27, 2014

Record last verified: 2014-06

Locations

US (7)