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

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.