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APOH is increased in the plasma and liver of type 2 diabetic patients with metabolic syndrome

  • Antoni Castro
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
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  • Iolanda Lázaro
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
    Search for articles by this author
  • David M. Selva
    Affiliations
    Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona Autonomous University, Barcelona, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
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  • Ela Céspedes
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain
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  • Josefa Girona
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
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  • NúriaPlana
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
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  • Montse Guardiola
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
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  • Anna Cabré
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
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  • Rafael Simó
    Affiliations
    Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona Autonomous University, Barcelona, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
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  • Lluís Masana
    Correspondence
    Corresponding author at: Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, C.Sant Llorenç 21, 43201 Reus, Spain. Tel.: +34 977759366; fax: +34 977759322.
    Affiliations
    Department of Internal Medicine and Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira & Virgili University, Reus, Spain

    CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
    Search for articles by this author

      Abstract

      Objective

      To assess the association of APOH with metabolic and cardiovascular risk markers in type 2 diabetic patients.

      Methods

      In a cohort of 169 type 2 diabetic subjects, plasma levels of APOH, antibodies anti-APOH, lipoprotein subfractions, oxidation, inflammatory and insulin resistance markers and the Trp316Ser and Val247Leu variations in the APOH gene were analyzed. Apo H mRNA levels and protein content were measured in hepatic and adipose tissue (subcutaneous and visceral) samples obtained during bariatric surgery from three diabetics who fulfilled metabolic syndrome (MS) criteria and three non-diabetic, non-MS.

      Results

      APOH plasma levels were significantly associated with triglycerides (p < 0.001), all the components of triglyceride-rich lipoproteins (p < 0.001) and RBP4 (p < 0.001) levels. APOH was higher in type 2 diabetic patients with MS (p = 0.003) and with clinical evidence of macrovascular disease (p = 0.012). The Trp316Ser and Val247Leu APOH gene variants did not modulate APOH plasma values. Neither Apo H mRNA nor protein was detected in the adipose tissue. Liver from patients with diabetes and MS showed a significant increase of both Apo H mRNA and protein respect to the non-diabetic, non-MS patients.

      Conclusion

      APOH plasma concentrations are strongly associated to MS alterations and vascular disease in type 2 diabetic patients and could be considered as a clinical marker of cardiovascular risk. The enhanced APOH levels in these patients are due to an increased liver synthesis. If APOH plays a major causal role in macrovascular lesions associated to diabetes and MS need further studies.

      Keywords

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