Journal
DIABETES
Volume 58, Issue 2, Pages 337-343Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db08-1228
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Funding
- National Institutes of Health [DK-24092]
- National Center for Research Resources [5K12RR023264]
- JPIC [AG-12834]
- University of Texas Health Science Center General Clinical Research Center [M01-RR-01346]
- Case Western Reserve University [T32 HL007887, T32 DK007319]
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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 . 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-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. Diabetes 58:337-343, 2009
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