早孕期胰岛素分泌增强反应。
Augmented insulin secretory response in early pregnancy.
机构信息
Diabetes Unit, Endocrine Division, Massachusetts General Hospital, 50 Staniford Street, Suite 301, Boston, MA, 02114, USA.
Harvard Medical School, Boston, MA, USA.
出版信息
Diabetologia. 2019 Aug;62(8):1445-1452. doi: 10.1007/s00125-019-4881-6. Epub 2019 Jun 9.
AIMS/HYPOTHESIS: This study aimed to examine changes in the insulin secretory response in early pregnancy, while accounting for changes in insulin sensitivity.
METHODS
This is a secondary analysis of a previously conducted longitudinal physiological study. In 34 women, insulin secretory response (by IVGTT) and insulin sensitivity (by euglycaemic clamp) were assessed prior to pregnancy, in early pregnancy (12-14 weeks gestation) and in late pregnancy (34-36 weeks gestation). Using mixed-effects models, we compared insulin secretory response and sensitivity in early pregnancy to the same variables prior to pregnancy and in late pregnancy, with adjustment for age, obesity status and gestational diabetes mellitus (GDM). We examined changes in insulin secretory response after adjustment for insulin sensitivity using both multivariate modelling and the disposition index (DI). We explored the relationship between insulin secretory response and circulating hormones.
RESULTS
The insulin secretory response increased from prior to pregnancy to early pregnancy (unadjusted mean [SD] first-phase insulin response 465.1 [268.5] to 720 [358.2], p < 0.0001) and from early pregnancy to late pregnancy (to 924 [494.6], p = 0.01). Insulin sensitivity increased from prior to pregnancy to early pregnancy (insulin sensitivity index 0.10 [0.04] to 0.12 [0.05], p = 0.001) and decreased in late pregnancy (to 0.06 [0.03], p < 0.0001). Accounting for changes in insulin sensitivity, using either multivariate modelling or the DI, did not attenuate the early-pregnancy augmentation of insulin secretory response. Leptin was positively associated with insulin secretory response, independent of insulin sensitivity and adiposity (p = 0.004). Adjustment for leptin attenuated the observed augmentation of insulin secretory response in early pregnancy (adjusted mean change 121.5, p = 0.13).
CONCLUSIONS/INTERPRETATION: The insulin secretory response increases markedly in early pregnancy, prior to and independent of changes in insulin sensitivity. Circulating hormones may mediate this metabolic adaptation. Identifying mediators of this physiological effect could have therapeutic implications for treating hyperglycaemia during and outside of pregnancy.
目的/假设：本研究旨在检查妊娠早期胰岛素分泌反应的变化，同时考虑到胰岛素敏感性的变化。
方法
这是一项先前进行的纵向生理研究的二次分析。在 34 名女性中，通过 IVGTT 评估胰岛素分泌反应（通过 IVGTT）和胰岛素敏感性（通过正葡萄糖钳夹），分别在妊娠前、妊娠早期（12-14 周妊娠）和妊娠晚期（34-36 周妊娠）进行。使用混合效应模型，我们比较了妊娠早期胰岛素分泌反应与妊娠前和妊娠晚期相同变量的胰岛素敏感性，调整了年龄、肥胖状态和妊娠期糖尿病（GDM）。我们使用多元模型和胰岛分泌指数（DI）来检查调整胰岛素敏感性后的胰岛素分泌反应的变化。我们还探讨了胰岛素分泌反应与循环激素之间的关系。
结果
与妊娠前相比，胰岛素分泌反应在妊娠早期增加（未经调整的平均[SD]第一时相胰岛素反应 465.1[268.5]至 720[358.2]，p<0.0001），并从妊娠早期到妊娠晚期增加（至 924[494.6]，p=0.01）。与妊娠前相比，胰岛素敏感性从妊娠早期增加（胰岛素敏感性指数 0.10[0.04]至 0.12[0.05]，p=0.001），并在妊娠晚期下降（至 0.06[0.03]，p<0.0001）。使用多元模型或 DI 来解释胰岛素敏感性的变化，并没有减弱妊娠早期胰岛素分泌反应的增强。瘦素与胰岛素分泌反应呈正相关，独立于胰岛素敏感性和肥胖程度（p=0.004）。调整瘦素后，观察到的妊娠早期胰岛素分泌反应增强减弱（调整后的平均变化 121.5，p=0.13）。
结论/解释：妊娠早期胰岛素分泌反应明显增加，早于并独立于胰岛素敏感性变化。循环激素可能介导这种代谢适应。鉴定这种生理效应的介质可能对治疗妊娠期间和之外的高血糖症具有治疗意义。
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