Ceramides are a family of lipid molecules comprising sphingosine bound to a fatty acid. They form an integral part of cell membranes and, according to cosmetics manufacturers, their inclusion in hair and skin care products can help you to maintain a ‘youthful glow’. In addition to their simple structural role, ceramides also act as signalling molecules with multiple effects and, of interest to the diabetes field, a potential role for ceramides in the pathogenesis of insulin resistance has recently emerged. Increased concentrations of ceramides have been reported in skeletal muscle of obese, insulin-resistant vs lean, insulin-sensitive men [1], and strong correlations have been observed between muscle ceramide concentrations and insulin sensitivity across a wide cross-section of insulin sensitivity values [2, 3]. However, this finding is not unequivocal with another study reporting no systematic differences in skeletal muscle ceramide concentrations among four groups of men—endurance trained, lean but untrained, obese and type 2 diabetic—although a weak correlation between ceramide concentration and insulin resistance was observed [4]. Ceramides may provide a key link between lipid oversupply, inflammation and insulin resistance, as a major determinant of ceramide synthesis is the availability of long-chain saturated fatty acids [5] and, in addition, a number of inflammatory cytokines, particularly TNF-α and IL-1, have been implicated in the regulation of ceramide production [5, 6]. In vitro studies indicate that ceramides inhibit insulin signalling in muscle cells, by decreasing insulin-stimulated activation of Akt/protein kinase B [5, 7] and by facilitating inflammatory signalling pathways known to impair insulin signalling [5, 6]. Furthermore, studies in human muscle cells [8] and rodents [9] indicate that blocking ceramide synthesis can prevent the development of insulin resistance. Thus, there is accumulating evidence that ceramides in skeletal muscle may be causally implicated in the pathogenesis of insulin resistance.

In this issue of Diabetologia, de Mello and colleagues [10] report a strong correlation between total plasma ceramide (measured by liquid chromatography–mass spectrometry) and serum IL-6 concentrations in a crosssectional study of 33 patients with cardiovascular disease. A modest, borderline significant correlation (r= 0.33, p= 0.06) between plasma ceramide levels and HOMA-