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Neues zur Pathobiochemie der diabetischen Dyslipidämie

Recent findings on the pathobiochemistry of diabetic dyslipidemia

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Zusammenfassung

Die diabetische Dyslipidämie stellt bei Menschen mit Typ-2-Diabetes einen wichtigen kardiovaskulären Risikofaktor dar. Verantwortlich für die Veränderungen im Lipidstoffwechsel ist insbesondere die Insulinresistenz, die die exzessive Bildung von großen, triglyzeridreichen Very-low-density-Lipoprotein(VLDL)-1-Partikeln und somit die Hypertriglyzeridämie begünstigt. Die erhöhten VLDL-Plasma-Spiegel entstehen zum einem durch vermehrte Produktion infolge des gesteigerten Zuflusses freier Fettsäuren zur Leber und zum anderen durch verminderten Abbau infolge von Insulinresistenz und niedrigem Adiponektinplasmaspiegel. Eine Ansammlung triglyzeridreicher Lipoproteine führt zur vermehrten Anzahl kleiner, dichter Low-density Lipoproteins („small-dense-LDL“, sdLDL) und verringerter Konzentration der Cholesterin rücktransportierenden High-density-Lipoprotein(HDL)-Partikel. Durch das Cholesterinestertransferprotein (CETP) wird der Austausch von Triglyzeriden der VLDL oder Chylomikronen gegen Cholesterinester der LDL- bzw. HDL-Partikel vermittelt. Durch Hydrolyse der triglyzeridreichen LDL bzw. HDL entsteht schließlich die atherogene Komposition aus sdLDL und kleineren, dysfunktionalen HDL-Partikeln, die rasch abgebaut werden.

Abstract

Diabetic dyslipidemia is an important cardiovascular risk factor in patients with type 2 diabetes. In particular insulin resistance, which favors excessive production of large, triglyceride-rich very-low-density lipoprotein (VLDL) 1 particles and consequently hypertriglyceridemia, is responsible for the alterations in lipid metabolism. Increased VLDL plasma levels result on the one hand from increased VLDL production due to the enhanced flow of free fatty acids to the liver and on the other hand from diminished VLDL degradation due to insulin resistance and low adiponectin plasma levels. The accumulation of triglyceride-rich lipoproteins causes an increased number of so-called small-dense LDLs (sdLDL) and a reduced concentration of high density lipoprotein (HDL) particles which transport cholesterol to the liver. The exchange of triglycerides from VLDL and chylomicrons for cholesteryl esters from LDLs and HDLs, respectively, is facilitated by cholesterylester transfer protein (CETP). Hydrolysis of triglyceride-rich LDLs and HDLs ultimately results in the atherogenic composition of sdLDL and small, dysfunctional HDL particles, which are rapidly metabolized.

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Authors and Affiliations

  1. Institut für Klinische Diabetologie, Leibniz-Zentrum für Diabetes-Forschung, Deutsches Diabetes-Zentrum, Heinrich-Heine-Universität, Auf’m Hennekamp 65, 40225, Düsseldorf, Deutschland

    M. Roden &  K. Müssig

  2. Klinik für Stoffwechselkrankheiten, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland

    F. Schwarz, M. Roden &  K. Müssig

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  1. F. Schwarz
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  2. M. Roden
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  3. K. Müssig
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Correspondence to K. Müssig.

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Schwarz, F., Roden, M. & Müssig, K. Neues zur Pathobiochemie der diabetischen Dyslipidämie. Diabetologe 8, 550–555 (2012). https://doi.org/10.1007/s11428-012-0888-z

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  • DOI: https://doi.org/10.1007/s11428-012-0888-z

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