精氨酸加压素缺乏症（中枢性尿崩症）患者和健康对照者对胰高血糖素的血浆催产素反应。

Plasma oxytocin levels in response to glucagon in patients with arginine vasopressin deficiency (central diabetes insipidus) and healthy controls.

机构信息

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.

出版信息

Endocrine. 2024 Nov;86(2):774-781. doi: 10.1007/s12020-024-03920-2. Epub 2024 Jun 27.

DOI:10.1007/s12020-024-03920-2

PMID:38935296

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11489228/

Abstract

PURPOSE

We recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using 3,4-methylenedioxy-methamphetamine (MDMA) as a novel provocation test. However, the implication of the MDMA provocation test in clinical practice might be challenging. Glucagon effectively stimulates vasopressinergic neurons with a strong increase in plasma copeptin. We therefore hypothesized that this provocation test might also stimulate OT.

METHODS

This is a predefined secondary analysis of a prospective double-blind, randomised, placebo-controlled cross-over trial involving ten patients with AVP deficiency and ten sex- and body-mass index-matched healthy participants at the University Hospital Basel, Switzerland. Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test (s.c. injection of 0.9% normal saline). Plasma OT levels were measured at baseline, 60, 120 and 180 min after injection. The primary objective was to determine whether glucagon stimulates OT and whether OT levels differ between patients with AVP deficiency and healthy participants. The primary outcome (maximum change in OT within 180 min) was compared between groups and conditions using a linear mixed effects model.

RESULTS

In healthy participants, the median OT at baseline was 82.7 pg/ml [62.3-94.3] and slightly increased to a maximum of 93.3 pg/ml [87.2-121.1] after injection of glucagon, resulting in a change increase of 24.9 pg/ml [5.1-27.8]. Similarly, in patients with AVP deficiency, the median OT at baseline was 73.9 pg/ml [65.3-81.6] and slightly increased after glucagon injection to 114.9 pg/ml [70.9-140.9], resulting in a change increase of 36.8 pg/ml [-2.2 to 51.2]. The results from the mixed model showed no effect between glucagon compared to placebo on OT (difference: -0.5 pg/ml; 95%-CI [-25, 24]; p = 0.97) and no significant treatment-by-group interaction effect between patients compared to healthy participants (interaction: 28 pg/ml; 95%-CI [-7, 62]; p = 0.13).

CONCLUSION

We found no effect of glucagon on plasma OT levels and no difference between patients with AVP deficiency and healthy participants.

摘要

目的

我们最近通过使用 3,4-亚甲二氧基甲基苯丙胺（MDMA）作为一种新的激发试验，证明了患有精氨酸加压素（AVP）缺乏症（中枢性尿崩症）的患者存在额外的催产素（OT）缺乏。然而，MDMA 激发试验在临床实践中的意义可能具有挑战性。胰高血糖素可有效刺激血管加压素能神经元，使血浆 copeptin 强烈增加。因此，我们假设该激发试验也可能刺激 OT。

方法

这是在瑞士巴塞尔大学医院进行的一项前瞻性双盲、随机、安慰剂对照交叉试验的预设二次分析，该试验涉及 10 名 AVP 缺乏症患者和 10 名性别和体重指数匹配的健康参与者。每位参与者接受胰高血糖素试验（皮下注射 1mg 胰高血糖素）和安慰剂试验（皮下注射 0.9%生理盐水）。在注射后 60、120 和 180 分钟测量血浆 OT 水平。主要目的是确定胰高血糖素是否刺激 OT，以及 OT 水平在 AVP 缺乏症患者和健康参与者之间是否存在差异。主要结局（180 分钟内 OT 的最大变化）通过线性混合效应模型在组间和条件间进行比较。

结果

在健康参与者中，基线时 OT 的中位数为 82.7pg/ml [62.3-94.3]，注射胰高血糖素后略有增加至最大值 93.3pg/ml [87.2-121.1]，增加 24.9pg/ml [5.1-27.8]。同样，在 AVP 缺乏症患者中，基线时 OT 的中位数为 73.9pg/ml [65.3-81.6]，注射胰高血糖素后略有增加至 114.9pg/ml [70.9-140.9]，增加 36.8pg/ml [-2.2 至 51.2]。混合模型的结果显示，与安慰剂相比，胰高血糖素对 OT 没有影响（差异：-0.5pg/ml；95%CI [-25, 24]；p=0.97），并且患者与健康参与者之间的治疗-组间交互作用也没有显著影响（交互作用：28pg/ml；95%CI [-7, 62]；p=0.13）。