Department of Physiology, Faculty of Medicine, University of Toronto, Ontario M5S 1A8, Canada.
Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, China.
J Clin Endocrinol Metab. 2022 Aug 18;107(9):2652-2665. doi: 10.1210/clinem/dgac346.
Prolactin is a multifaceted hormone known to regulate lactation. In women with gestational diabetes mellitus (GDM) history, intensive lactation has been associated with lower relative risk of future type 2 diabetes (T2D). However, the role of prolactin in T2D development and maternal metabolism in women with a recent GDM pregnancy has not been ascertained.
We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters.
We utilized a prospective GDM research cohort (the SWIFT study) and followed T2D onset by performing 2-hour 75-g research oral glucose tolerance test (OGTT) at study baseline (6-9 weeks postpartum) and again annually for 2 years, and also by retrieving clinical diagnoses of T2D from 2 years through 10 years of follow up from electronic medical records. Targeted metabolomics and lipidomics were applied on fasting plasma samples collected at study baseline from 2-hour 75-g research OGTTs in a nested case-control study (100 future incident T2D cases vs 100 no T2D controls).
Decreasing prolactin quartiles were associated with increased future T2D risk (adjusted odds ratio 2.48; 95% CI, 0.81-7.58; P = 0.05). In women who maintained normoglycemia during the 10-year follow-up period, higher prolactin at baseline was associated with higher insulin sensitivity (P = 0.038) and HDL-cholesterol (P = 0.01), but lower BMI (P = 0.001) and leptin (P = 0.002). Remarkably, among women who developed future T2D, prolactin was not correlated with a favorable metabolic status (all P > 0.05). Metabolomics and lipidomics showed that lower circulating prolactin strongly correlated with a T2D-high risk lipid profile, with elevated circulating neutral lipids and lower concentrations of specific phospholipids/sphingolipids.
In women with recent GDM pregnancy, low circulating prolactin is associated with specific clinical and metabolic parameters and lipid metabolites linked to a high risk of developing T2D.
催乳素是一种多效激素，已知其可调节泌乳。在有妊娠糖尿病史的女性中，强化哺乳与未来发生 2 型糖尿病（T2D）的相对风险较低有关。然而，催乳素在近期患有 GDM 妊娠的女性的 T2D 发病机制和母体代谢中的作用尚未确定。
我们研究了催乳素与未来 T2D 风险以及关键临床和代谢参数之间的关系。
我们利用了一个前瞻性的 GDM 研究队列（SWIFT 研究），通过在研究基线（产后 6-9 周）时进行 2 小时 75g 研究口服葡萄糖耐量试验（OGTT），并在接下来的 2 年内每年进行一次，以及通过从电子病历中检索 2 年至 10 年的随访期间的 T2D 临床诊断，来检测 T2D 的发病情况。在一个巢式病例对照研究（100 例未来的 T2D 病例与 100 例无 T2D 对照）中，对从 2 小时 75g 研究 OGTT 中收集的空腹血浆样本进行靶向代谢组学和脂质组学分析。
催乳素四分位值降低与未来 T2D 风险增加相关（校正后的优势比 2.48；95%CI，0.81-7.58；P=0.05）。在 10 年随访期间血糖持续正常的女性中，基线时催乳素较高与胰岛素敏感性较高（P=0.038）和高密度脂蛋白胆固醇较高（P=0.01）相关，但体重指数较低（P=0.001）和瘦素较低（P=0.002）。值得注意的是，在发生未来 T2D 的女性中，催乳素与有利的代谢状态无关（均 P＞0.05）。代谢组学和脂质组学研究表明，循环中催乳素水平降低与 T2D 高风险脂质谱密切相关，表现为循环中性脂质升高和特定磷脂/鞘脂浓度降低。
在近期患有 GDM 妊娠的女性中，循环中催乳素水平较低与特定的临床和代谢参数以及与发生 T2D 风险较高相关的脂质代谢物相关。
