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Metabolic Phenotypes, Vascular Complications, and Premature Deaths in a Population of 4,197 Patients With Type 1 Diabetes

  1. Ville-Petteri Mäkinen123,
  2. Carol Forsblom23,
  3. Lena M. Thorn23,
  4. Johan Wadén23,
  5. Daniel Gordin23,
  6. Outi Heikkilä23,
  7. Kustaa Hietala23,
  8. Laura Kyllönen23,
  9. Janne Kytö23,
  10. Milla Rosengård-Bärlund23,
  11. Markku Saraheimo23,
  12. Nina Tolonen23,
  13. Maija Parkkonen23,
  14. Kimmo Kaski1,
  15. Mika Ala-Korpela123,
  16. Per-Henrik Groop23 and
  17. on behalf of the FinnDiane Study Group*
  1. 1Department of Biomedical Engineering and Computational Science, Helsinki University of Technology, Helsinki, Finland
  2. 2Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
  3. 3Division of Nephrology, Department of Medicine, Helsinki University Hospital, Helsinki, Finland
  1. Corresponding authors: Ville-Petteri Mäkinen, ville-petteri.makinen{at}computationalmedicine.fi; and Per-Henrik Groop, per-henrik.groop{at}helsinki.fi

Abstract

OBJECTIVE—Poor glycemic control, elevated triglycerides, and albuminuria are associated with vascular complications in diabetes. However, few studies have investigated combined associations between metabolic markers, diabetic kidney disease, retinopathy, hypertension, obesity, and mortality. Here, the goal was to reveal previously undetected association patterns between clinical diagnoses and biochemistry in the FinnDiane dataset.

RESEARCH DESIGN AND METHODS—At baseline, clinical records, serum, and 24-h urine samples of 2,173 men and 2,024 women with type 1 diabetes were collected. The data were analyzed by the self-organizing map, which is an unsupervised pattern recognition algorithm that produces a two-dimensional layout of the patients based on their multivariate biochemical profiles. At follow-up, the results were compared against all-cause mortality during 6.5 years (295 deaths).

RESULTS—The highest mortality was associated with advanced kidney disease. Other risk factors included 1) a profile of insulin resistance, abdominal obesity, high cholesterol, triglycerides, and low HDL2 cholesterol, and 2) high adiponectin and high LDL cholesterol for older patients. The highest population-adjusted risk of death was 10.1-fold (95% CI 7.3–13.1) for men and 10.7-fold (7.9–13.7) for women. Nonsignificant risk was observed for a profile with good glycemic control and high HDL2 cholesterol and for a low cholesterol profile with a short diabetes duration.

CONCLUSIONS—The self-organizing map analysis enabled detailed risk estimates, described the associations between known risk factors and complications, and uncovered statistical patterns difficult to detect by classical methods. The results also suggest that diabetes per se, without an adverse metabolic phenotype, does not contribute to increased mortality.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 19 June 2008.

  • *

    * A complete listing of the FinnDiane Study Group can be found in the online appendix available at http://dx.doi.org/10.2337/db08-0332.

  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 22, 2008.
    • Received March 7, 2008.
| Table of Contents

This Article

  1. Diabetes September 2008 vol. 57 no. 9 2480-2487
  1. » Abstract
  2. Online-Only Appendix
  3. All Versions of this Article:
    1. db08-0332v1
    2. db08-0332v2
    3. 57/9/2480 most recent

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