Accumulation 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,... Show moreAccumulation 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. Show less
Taherzadeh, Z.; VanBavel, E.; Vos, J. de; Matlung, H.L.; Montfrans, G. van; Brewster, L.M.; ... ; Bakker, E.N.T.P. 2010
Taherzadeh Z, VanBavel E, de Vos J, Matlung HL, van Montfrans G, Brewster LM, Seghers L, Quax PH, Bakker EN. Strain-dependent susceptibility for hypertension in mice resides in the natural killer... Show moreTaherzadeh Z, VanBavel E, de Vos J, Matlung HL, van Montfrans G, Brewster LM, Seghers L, Quax PH, Bakker EN. Strain-dependent susceptibility for hypertension in mice resides in the natural killer gene complex. Am J Physiol Heart Circ Physiol 298: H1273-H1282, 2010. First published February 12, 2010; doi: 10.1152/ajpheart. 00508.2009.-Hypertension is associated with chronic vascular inflammation. We tested the hypothesis that the sensitivity to develop hypertension and vascular remodeling depends on the immunological background. Blood pressure, vascular remodeling, endothelial function, vascular architecture ( number of collateral arteries), and expression of inflammatory cytokines were determined in mice that received N-G-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthesis. We studied C57BL/6, BALB/c, and BALB. B6-Cmv1r mice, a congenic strain where the natural killer (NK) gene complex of C57BL/6 mice is introduced in the BALB/c background. During a 4-wk treatment with L-NAME, blood pressure initially increased in both C57BL/6 and BALB/C mice, but after 4 wk, only C57BL/6 mice showed a significant increase in mean arterial blood pressure (+53 mmHg; P < 0.001) and small artery inward remodeling. Endothelial function and vascular design were significantly different between C57BL/6 mice and BALB/C mice. The inflammatory response was similar in C57BL/6 and BALB/C mice, except for the leukocyte marker CD11b. Cellular colocalization of CD11b with NK1.1 indicated the recruitment of NK cells in C57BL/6 mice. Congenic BALB. B6-Cmv1r mice showed the same endothelial response and vascular architecture as BALB/c mice. However, BALB. B6-Cmv1r mice displayed a similar sensitivity to hypertension and vascular remodeling as C57BL/6 mice. In conclusion, we have identified the NK gene complex as an important determinant in the genetically determined sensitivity to develop L-NAME-induced hypertension in mice. Show less
