AbstractAccumulation of metabolites may mark or contribute to the development of type 2 diabetes mellitus (T2D), but there is a lack of data from ethnic groups at high risk. We examined sphingolipids, acylcarnitines and amino acids, and their association with T2D in a nested case–control study among 54 South Asian Surinamese, 54 African Surinamese and 44 Dutch in the Netherlands. Plasma metabolites were determined at baseline (2001–2003), and cumulative prevalence and incidence of T2D at follow-up (2011–2012). Weighted linear and logistic regression analyses were used to study associations. The mean level of most sphingolipids was lower, and amino-acid levels higher, in the Surinamese groups than among the Dutch. Surinamese individuals had higher mono- and polyunsaturated acylcarnitines and lower plasma levels of saturated acylcarnitine species than the Dutch. Several sphingolipids and amino acids were associated with T2D. Although only the shorter acylcarnitines seemed associated with prevalent T2D, we found an association of all acylcarnitines (except C0, C18 and C18:2) with incident T2D. Further analyses suggested a potentially different association of several metabolites across ethnic groups. Extension and confirmation of these findings may improve the understanding of ethnic differences and contribute to early detection of increased individual risk.