Plasma Ceramides Are Elevated in Obese Subjects With Type 2 Diabetes and Correlate With the Severity of Insulin Resistance
By J. Haus, S. Kashyap, T. Kasumov, Renliang Zhang, K. Kelly, Ralph DeFronzo, J. Kirwan. Diabetes, 2009
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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-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.
Subfields: Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/bef1aa46aa75dce9cf93079c7280b5a238fea428
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Citations in the corpus
- Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009 (2010, background): “Muscle [150] and plasma [151] ceramide levels are also increased in obese and type 2 diabetic individuals, correlating closely with severity of insulin resistance.”
- Insulin receptor signaling in normal and insulin-resistant states. (2014, background): “Increased plasma concentration of the sphingolipid ceramide is observed in obese and diabetic patients and is associated with severe insulin resistance (Haus et al. 2009).”
- The cellular and signaling networks linking the immune system and metabolism in disease (2012, result): “, consistent with earlier work that showed positive correlations between the amounts of cytokines and ceramide in plasma and insulin resistanc”