Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance.

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  • Additional Information
    • Source:
      Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
    • Publication Information:
      Publication: Alexandria, VA : American Diabetes Association
      Original Publication: [New York, American Diabetes Association]
    • Subject Terms:
      Ceramides/*blood ; Diabetes Mellitus, Type 2/*blood ; Insulin Resistance/*physiology ; Obesity/*blood; Adult ; Ceramides/chemistry ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Type 2/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Obesity/physiopathology ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; Tumor Necrosis Factor-alpha/blood
    • Abstract:
      Objective: To quantitate plasma ceramide subspecies concentrations in obese subjects with type 2 diabetes and relate these plasma levels to the severity of insulin resistance. Ceramides are a putative mediator of insulin resistance and lipotoxicity, and accumulation of ceramides within tissues in obese and diabetic subjects has been well described.
      Research Design and Methods: We analyzed fasting plasma ceramide subspecies by quantitative tandem mass spectrometry in 13 obese type 2 diabetic patients and 14 lean healthy control subjects. Results were related to insulin sensitivity measured with the hyperinsulinemic-euglycemic clamp technique and with plasma tumor necrosis factor-alpha (TNF-alpha) levels, a marker of inflammation. Ceramide species (C18:1, 18:0, 20:0, 24:1, and 24:0) were quantified using electrospray ionization tandem mass spectrometry after separation with high-performance liquid chromatography.
      Results: Insulin sensitivity (mg x kg(-1) x min(-1)) was lower in type 2 diabetic patients (4.90 +/- 0.3) versus control subjects (9.6 +/- 0.4) (P < 0.0001). Type 2 diabetic subjects had higher (P < 0.05) concentrations of C18:0, C20:0, C24:1, and total ceramide. Insulin sensitivity was inversely correlated with C18:0, C20:0, C24:1, C24:0, and total ceramide (all P < 0.01). Plasma TNF-alpha concentration was increased (P < 0.05) in type 2 diabetic subjects and correlated with increased C18:1 and C18:0 ceramide subspecies.
      Conclusions: Plasma ceramide levels are elevated in type 2 diabetic subjects and may contribute to insulin resistance through activation of inflammatory mediators, such as TNF-alpha.
    • Comments:
      Comment in: Diabetes. 2009 Feb;58(2):307-8. (PMID: 19171748)
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    • Grant Information:
      M01-RR-01346 United States RR NCRR NIH HHS; R01 DK024092 United States DK NIDDK NIH HHS; 5K12RR023264 United States RR NCRR NIH HHS; AG-12834 United States AG NIA NIH HHS; DK-24092 United States DK NIDDK NIH HHS; R56 DK024092 United States DK NIDDK NIH HHS; T32 HL007887 United States HL NHLBI NIH HHS; R01 AG012834 United States AG NIA NIH HHS; T32 DK007319 United States DK NIDDK NIH HHS; M01 RR001346 United States RR NCRR NIH HHS; K12 RR023264 United States RR NCRR NIH HHS; R29 AG012834 United States AG NIA NIH HHS
    • Accession Number:
      0 (Ceramides)
      0 (Tumor Necrosis Factor-alpha)
    • Publication Date:
      Date Created: 20081115 Date Completed: 20090331 Latest Revision: 20240511
    • Publication Date:
      20240511
    • Accession Number:
      PMC2628606
    • Accession Number:
      10.2337/db08-1228
    • Accession Number:
      19008343