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

Jacob M. Haus, Sangeeta R. Kashyap, Takhar Kasumov, Renliang Zhang, Karen R. Kelly, Ralph A. Defronzo, John P. Kirwan

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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-α (TNF-α) 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 · kg -1 · 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-α 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-α.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
JournalDiabetes
Volume58
Issue number2
DOIs
StatePublished - Feb 1 2009

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Haus, J. M., Kashyap, S. R., Kasumov, T., Zhang, R., Kelly, K. R., Defronzo, R. A., & Kirwan, J. P. (2009). Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes, 58(2), 337-343. https://doi.org/10.2337/db08-1228