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Altered plasma serine and 1-deoxydihydroceramide profiles are associated with diabetic neuropathy in type 2 diabetes and obesity

2021; Elsevier BV; Volume: 35; Issue: 4 Linguagem: Inglês

10.1016/j.jdiacomp.2021.107852

1873-460X

Vera Fridman, Simona Zarini, Stefan Sillau, Kathleen A. Harrison, Bryan C. Bergman, Eva L. Feldman, Jane E.B. Reusch, Brian C. Callaghan,

Sleep and Wakefulness Research

Recent studies suggest that the accumulation of atypical, 1-deoxysphingolipids that lack the C1 hydroxyl group may be associated with diabetic neuropathy (DN). We hypothesized that specific plasma 1-deoxysphingolipids associate with DN severity, and that alterations in plasma serine and alanine associate with 1-deoxysphingolipid elevation in patients with type 2 diabetes (T2D). We examined individual 1-deoxysphingolipid species using LC/MS/MS in plasma samples from 75 individuals including lean controls (LC, n = 19), those with obesity (n = 19), obesity with T2D without DN (ob/T2D, n = 18), and obesity with T2D with DN (Ob/T2D/DN, n = 19). We observed a step wise increase in 1-deoxydihydroceramides across these four groups (spearman correlation coefficient r = 0.41, p = 0.0002). Mean total concentrations of 1-deoxydihydroceramides, and most individual 1-deoxydihydroceramide species, were higher in ob/T2D/DN versus LC group (8.939 vs. 5.195 pmol/100 μL for total 1-deoxydihydroceramides p = 0.005). No significant differences in 1-deoxydihydroceramides were observed between the ob/T2D and ob/T2D/DN groups. l-alanine was higher and l-serine lower in ob/T2D/DN versus LC groups (326.2 vs. 248.0 μM, p = 0.0086 and 70.2 vs. 89.8 μM, p = 0.0110), consistent with a potential contribution of these changes to the observed 1-deoxysphingolipids profiles. 1-deoxydihydroceramides correlated inversely with leg intraepidermal nerve fiber density (CC -0.40, p = 0.003). These findings indicate that 1-deoxydihydroceramides may be important biomarkers and/or mediators of DN.