Table 1_Association of overweight/obesity and insulin resistance with activation of circulating innate lymphoid cells in women after gestational diabetes mellitus.pdf

IntroductionWomen with a history of gestational diabetes mellitus (GDM) are at high risk of developing prediabetes or type 2 diabetes later in life. Recent studies have highlighted the regulation and function of innate lymphoid cells (ILCs) in metabolic homeostasis. However, the multifactorial impact of both overweight/obesity and GDM on the immunological profile of circulating ILCs and the progression to prediabetes are not yet fully elucidated.
MethodsBlood samples from 42 women with a history of insulin-treated GDM (GDMi), 33 women with a history of GDM without insulin treatment during pregnancy (GDM), and 45 women after a normoglycemic pregnancy (Ctrl) participating in the ongoing observational PPSDiab study were analyzed by flow cytometry for markers of ILC subsets at the baseline visit (3-16 months postpartum; Visit 1) and 5 years postpartum (58-66 months postpartum; Visit 2).
ResultsDuring the first 5 years postpartum, 18 women of the GDMi group (42.8%), 10 women of the GDM group (30.3%), and 8 participants of the Ctrl group (17.8%) developed prediabetes, respectively. Total circulating type 1 innate lymphoid cells (ILC1s) and NK cell numbers as well as percent HLA-DR+ ILC1s were increased in GDMi versus GDM and Ctrl women both at the baseline visit and the 5-year follow-up. Although ILC subsets at Visit 1 could not predict the progression from GDM to prediabetes, ILC2 frequency was associated with insulin sensitivity index (ISI), whereas percent HLA-DR+ ILC1s were inversely correlated. Moreover, circulating leukocytes and total NK cells were associated with waist circumference and fat mass both at Visit 1 and Visit 2.
DiscussionOur findings introduce human ILCs as a potential therapeutic target deserving further exploration.
Trial registrationStudy ID 300-11.

【引言】曾患妊娠糖尿病（gestational diabetes mellitus, GDM）的女性，在日后发生糖尿病前期或2型糖尿病的风险显著升高。近期研究已证实固有淋巴样细胞（innate lymphoid cells, ILCs）在代谢稳态中的调控作用与功能。然而，超重/肥胖与妊娠糖尿病二者对循环固有淋巴样细胞免疫特征的多因素影响，以及其向糖尿病前期的进展机制，目前尚未完全阐明。
【研究方法】本研究纳入正在进行的观察性研究PPSDiab中的受试者，分为三组：42例曾接受胰岛素治疗的妊娠糖尿病（insulin-treated GDM, GDMi）女性、33例妊娠期未接受胰岛素治疗的妊娠糖尿病（GDM）女性，以及45例血糖正常妊娠史女性（对照组, Ctrl）。分别在基线访视（产后3~16个月，访视1）与产后5年（产后58~66个月，访视2）两个时间点采集血液样本，通过流式细胞术检测固有淋巴样细胞亚群的标志物。
【研究结果】产后前5年随访期间，GDMi组、GDM组与对照组分别有18例（42.8%）、10例（30.3%）与8例（17.8%）受试者进展为糖尿病前期。在基线访视与5年随访两个时间点，GDMi组的循环1型固有淋巴样细胞（type 1 innate lymphoid cells, ILC1s）与自然杀伤（NK）细胞总数，以及HLA-DR阳性ILC1s的占比，均高于GDM组与对照组。尽管访视1时的固有淋巴样细胞亚群无法预测GDM向糖尿病前期的进展，但ILC2的细胞频率与胰岛素敏感性指数（insulin sensitivity index, ISI）呈正相关，而HLA-DR阳性ILC1s的占比则呈负相关。此外，访视1与访视2两个时间点的循环白细胞总数与NK细胞总数，均与腰围及体脂量存在相关性。
【讨论】本研究结果提示，人固有淋巴样细胞可作为潜在的治疗靶点，有待进一步深入探索。
【试验注册】研究编号：300-11。