Muilwijk Mirthe, Goorden Susan M I, Celis-Morales Carlos, Hof Michel H, Ghauharali-van der Vlugt Karen, Beers-Stet Femke S, Gill Jason M R, Vaz Frédéric M, van Valkengoed Irene G M
Department of Public Health, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
BMJ Open Diabetes Res Care. 2020 May;8(1). doi: 10.1136/bmjdrc-2019-001003.
People of South Asian origin are at high risk of type 2 diabetes (T2D), but the underpinning mechanisms are not fully understood. We determined ethnic differences in acylcarnitine, amino acid and sphingolipid concentrations and determined the associations with T2D.
Associations between these metabolites and incident T2D among Dutch and South-Asian Surinamese were determined in participants from the Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands) using Prentice-weighted Cox regression. The HELIUS study includes 95 incident T2D cases and a representative subcohort of 700 people from a cohort of 5977 participants with a mean follow-up of 4 years.
Concentrations of acylcarnitines were comparable between both ethnic groups. Amino acid and lactosylceramide concentrations were higher among South-Asian Surinamese than Dutch (eg, isoleucine 65.7 (SD 16.3) vs 60.7 (SD 15.6) µmol/L). Ceramide concentrations were lower among South-Asian Surinamese than Dutch (eg, Cer d18:1 8.48 (SD 2.04) vs 9.08 (SD 2.29) µmol/L). Metabolic dysregulation preceded T2D without evidence for a multiplicative interaction by ethnicity. Most amino acids and (dihydro)ceramides were associated with increased risk (eg, Cer d18:1 HR 2.38, 95% CI 1.81 to 3.12) while acylcarnitines, glycine, glutamine and lactosylceramides were associated with decreased risk for T2D (eg, LacCer d18:2 HR 0.56, 95% CI 0.42 to 0.77).
Overall, these data suggest that the disturbances underlying amino acid and sphingolipid metabolism may be predictive of T2D risk in populations of both South Asian and European background. These observations may be used as starting point to unravel the underlying metabolic disturbances.
南亚裔人群患2型糖尿病(T2D)的风险很高,但其潜在机制尚未完全明确。我们确定了酰基肉碱、氨基酸和鞘脂浓度的种族差异,并确定了它们与T2D的关联。
在荷兰开展的“城市环境中的健康生活”(HELIUS)研究(荷兰阿姆斯特丹)的参与者中,采用Prentice加权Cox回归分析这些代谢物与荷兰人和南亚苏里南人新发T2D之间的关联。HELIUS研究纳入了95例新发T2D病例,以及从5977名参与者队列中选取的700人代表性亚队列,平均随访4年。
两个种族群体的酰基肉碱浓度相当。南亚苏里南人的氨基酸和乳糖神经酰胺浓度高于荷兰人(例如,异亮氨酸65.7(标准差16.3)对60.7(标准差15.6)μmol/L)。南亚苏里南人的神经酰胺浓度低于荷兰人(例如,神经酰胺d18:1 8.48(标准差2.04)对9.08(标准差2.29)μmol/L)。代谢失调先于T2D出现,且没有证据表明存在种族间的相乘交互作用。大多数氨基酸和(二氢)神经酰胺与风险增加相关(例如,神经酰胺d18:1风险比2.38,95%置信区间1.81至3.12),而酰基肉碱、甘氨酸、谷氨酰胺和乳糖神经酰胺与T2D风险降低相关(例如,乳糖神经酰胺d18:2风险比0.56,95%置信区间0.42至0.77)。
总体而言,这些数据表明,氨基酸和鞘脂代谢的紊乱可能预示着南亚和欧洲背景人群患T2D的风险。这些观察结果可作为揭示潜在代谢紊乱的起点。