Triglyceride-cholesterol imbalance across lipoprotein subclasses predicts diabetic kidney disease and mortality in type 1 diabetes: the FinnDiane Study

Authors

  • V.-P. Mäkinen,

    Corresponding author
    1. Biocenter Oulu, University of Oulu, Oulu, Finland
    2. Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland
    3. Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
    4. College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan Province, China
    • Computational Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
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  • P. Soininen,

    1. Computational Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
    2. NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
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  • A. J. Kangas,

    1. Computational Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
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  • C. Forsblom,

    1. Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland
    2. Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
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  • N. Tolonen,

    1. Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland
    2. Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
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  • L. M. Thorn,

    1. Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland
    2. Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
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  • J. Viikari,

    1. Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland
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  • O. T. Raitakari,

    1. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
    2. Department of Clinical Physiology, University of Turku and Turku University Hospital, Turku, Finland
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  • M. Savolainen,

    1. Computational Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
    2. Biocenter Oulu, University of Oulu, Oulu, Finland
    3. Department of Internal Medicine, Clinical Research Center, University of Oulu, Oulu, Finland
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  • P.-H. Groop,

    1. Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
    2. College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan Province, China
    3. Baker IDI Heart and Diabetes Institute, Melbourne, Australia
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  • M. Ala-Korpela,

    1. Computational Medicine, Institute of Clinical Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland
    2. College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan Province, China
    3. Department of Internal Medicine, Clinical Research Center, University of Oulu, Oulu, Finland
    4. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
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  • Finnish Diabetic Nephropathy Study Group


Correspondence: Ville-Petteri Mäkinen, DSc (Tech), Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, PO Box 63, FI-00014, Finland.

(fax: +358 9 19125452; e-mail: ville-petteri.makinen@computationalmedicine.fi).

Abstract

Background

Circulating cholesterol (C) and triglyceride (TG) levels are associated with vascular injury in type 1 diabetes (T1DM). Lipoproteins are responsible for transporting lipids, and alterations in their subclass distributions may partly explain the increased mortality in individuals with T1DM.

Design and subjects

A cohort of 3544 individuals with T1DM was recruited by the nationwide multicentre FinnDiane Study Group. At baseline, six very low-density lipoprotein VLDL, one intermediate-density lipoprotein IDL, three low-density lipoprotein LDL and four higher high-density lipoprotein HDL subclasses were quantified by proton nuclear magnetic resonance spectroscopy. At follow-up, the baseline data were analysed for incident micro- or macroalbuminuria (117 cases in 5.3 years), progression from microalbuminuria (63 cases in 6.1 years), progression from macroalbuminuria (109 cases in 5.9 years) and mortality (385 deaths in 9.4 years). Univariate associations were tested by age-matched cases and controls and multivariate lipoprotein profiles were analysed using the self-organizing map (SOM).

Results

TG and C levels in large VLDL were associated with incident albuminuria, TG and C in medium VLDL were associated with progression from microalbuminuria, and TG and C in all VLDL subclasses were associated with mortality. Large HDL-C was inversely associated with mortality. Three extreme phenotypes emerged from SOM analysis: (i) low C (<3% mortality), (ii) low TG/C ratio (6% mortality), and (iii) high TG/C ratio (40% mortality) in all subclasses.

Conclusions

TG–C imbalance is a general lipoprotein characteristic in individuals with T1DM and high vascular disease risk.

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