Journal of Diabetes and Its Complications
Volume 25, Issue 6 , Pages 355-361, November 2011

The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial☆☆☆

  • William C. Duckworth

      Affiliations

    • Phoenix VA Health Care Center, Phoenix, AZ 85012, USA
    • Corresponding Author InformationCorresponding author. Fax: +1 602 200 6004.
    • ,
  • Carlos Abraira

      Affiliations

    • Miami VA Medical Center, Miami, FL, USA
    • ,
  • Thomas E. Moritz

      Affiliations

    • Hines VA Cooperative Studies Program (CSP) Coordinating Center, Hines, IL, USA
    • ,
  • Stephen N. Davis

      Affiliations

    • Tennessee Valley Health Care System, Nashville, TN, USA
    • ,
  • Nicholas Emanuele

      Affiliations

    • Hines VA Hospital, Hines, IL, USA
    • ,
  • Steven Goldman

      Affiliations

    • Southern Arizona VA Health Care System, Tucson, AZ, USA
    • ,
  • Rodney Hayward

      Affiliations

    • VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
    • ,
  • Grant D. Huang

      Affiliations

    • Cooperative Studies Program Central Office, VA Office of Research and Development, Washington, DC, USA
    • ,
  • Jennifer B. Marks

      Affiliations

    • Miami VA Medical Center, Miami, FL, USA
    • ,
  • Peter D. Reaven

      Affiliations

    • Phoenix VA Health Care Center, Phoenix, AZ 85012, USA
    • ,
  • Domenic J. Reda

      Affiliations

    • Hines VA Cooperative Studies Program (CSP) Coordinating Center, Hines, IL, USA
    • ,
  • Stuart R. Warren

      Affiliations

    • VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, NM, USA
    • ,
  • Franklin J. Zieve

      Affiliations

    • Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA
    • ,
  • for the Investigators of the VADT

Received 15 October 2010; received in revised form 5 October 2011; accepted 7 October 2011. published online 07 November 2011.

Abstract 

Background

The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult-to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population.

Methods

This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat.

Findings

Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P<.0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR >1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77–3.320, P<.01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently.

Interpretation

In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration.

Keywords: Type 2 diabetes, Intensive glucose control, Macrovascular risk and events

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☆ A portion of these data was presented at the June 2009 Annual Meeting of the ADA in New Orleans, LA, USA.

☆☆ This study was supported by the VA Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development. All rights are reserved by the United States Department of Veteran Affairs. All authors have filed conflict-of-interest statements. Additional support was received from the American Diabetes Association and the National Eye Institute of the NIH. Pharmaceutical, other supplies, and financial assistance were provided by GlaxoSmithKline, Novo Nordisk, Roche Diagnostics, Sanofi-Aventis, Amylin, and Kos Pharmaceuticals. The assistance of the co-chairs' coordinators, Susan Collier (Phoenix) and Christina Paul (Miami), in the preparation of this manuscript is gratefully acknowledged. Lizy Thottapurathu (Hines) assisted in the data analysis. Special recognition is given to Rebecca Miller (Phoenix), Georgia Roode (Phoenix), and Janet Fawcett, Ph.D. (Phoenix), for preparing the final draft and for consistent support throughout the study, and to our veterans who participated in and made possible this study.

PII: S1056-8727(11)00125-5

doi:10.1016/j.jdiacomp.2011.10.003

Journal of Diabetes and Its Complications
Volume 25, Issue 6 , Pages 355-361, November 2011

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