Grannes Helene, Sharma Archana, Suntharalingam Anita, Michelsen Annika E, Aukrust Pål, Ueland Thor, Birkeland Kåre I, Gregersen Ida, Lee-Ødegård Sindre, Halvorsen Bente
Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Heliyon. 2024 Nov 16;10(22):e40339. doi: 10.1016/j.heliyon.2024.e40339. eCollection 2024 Nov 30.
Women with South Asian ethnicity have a higher risk of developing type 2 diabetes mellitus (T2DM) compared with white women of European descent, especially after gestational diabetes mellitus (GDM). Central obesity and adipose tissue dysfunction have been linked to their higher risk of T2DM, but the mechanisms are not known. We hypothesize that low-grade, persistent immune cell activation is involved in metabolic disturbances following GDM with different influence according to ethnicity.
We measured plasma levels of T cell exhaustion (sTIM-3), sCD25, sCD27 and soluble lymphocyte activation gene (sLAG)-3 in 266 women of South Asian (n = 160) and white Nordic (n = 106) ethnic background with a history of GDM.
Baseline plasma concentration of sTIM-3 was higher in South Asian women compared to Nordic women (p < 0.001). This difference was driven by higher sTIM-3 in South Asian women with NGT, compared to their Nordic counterparts (p = 0.005) but there were no significant differences comparing Nordic and South Asian women with altered glucose tolerance (AGT). Soluble TIM-3 correlated positively with waist-height ratio (WHtR) and body mass index across all groups, but whereas sTIM-3 correlated moderately and consistently with markers of metaflammation in South Asians, this pattern was not found in Nordic women. Mediation analysis indicated that 15 % of the difference found in adipose insulin resistance between ethnicities could be mediated by sTIM-3, and that 33 % of the difference in sTIM-3 concentrations could be mediated by WHtR. Moreover, T cell markers sCD27 and sLAG3 were also increased in South Asian women compared with Nordic women, further supporting involvement of T cell activation in these women.
We found increased levels of sTIM-3, as well as additional markers of T cell activation/exhaustion, in a population of normoglycemic South Asian women with previous gestational diabetes as compared to women of Nordic descent. The possible causal relationship between T cell activation and metabolic dysfunction in high-risk South Asian women is however still elusive and merits further investigation.
与欧洲裔白人女性相比，南亚裔女性患2型糖尿病（T2DM）的风险更高，尤其是在患有妊娠期糖尿病（GDM）之后。中心性肥胖和脂肪组织功能障碍与她们患T2DM的较高风险有关，但其机制尚不清楚。我们推测，低度、持续性免疫细胞激活参与了GDM后的代谢紊乱，且根据种族不同有不同影响。
我们测量了266名有GDM病史的南亚（n = 160）和北欧白人（n = 106）种族背景女性的血浆T细胞耗竭标志物（sTIM-3）、sCD25、sCD27和可溶性淋巴细胞激活基因（sLAG）-3水平。
与北欧女性相比，南亚女性的sTIM-3基线血浆浓度更高（p < 0.001）。这种差异是由血糖正常的南亚女性中较高的sTIM-3水平驱动的，与北欧女性相比（p = 0.005），但在糖耐量异常（AGT）的北欧和南亚女性之间没有显著差异。在所有组中，可溶性TIM-3与腰高比（WHtR）和体重指数呈正相关，但在南亚人中，sTIM-3与亚炎症标志物呈中度且持续的相关性，而在北欧女性中未发现这种模式。中介分析表明，种族间脂肪胰岛素抵抗差异的15%可由sTIM-3介导，sTIM-3浓度差异的33%可由WHtR介导。此外，与北欧女性相比，南亚女性的T细胞标志物sCD27和sLAG3也有所增加，进一步支持了T细胞激活参与这些女性的情况。
我们发现，与北欧裔女性相比，有既往妊娠期糖尿病的血糖正常的南亚女性群体中sTIM-3水平升高，以及T细胞激活/耗竭的其他标志物升高。然而，高危南亚女性中T细胞激活与代谢功能障碍之间可能的因果关系仍不明确，值得进一步研究。
