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

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine Pub Date : 2024-11-01 Epub Date: 2024-06-27 DOI:10.1007/s12020-024-03920-2

Cihan Atila, Shalini Mekkattu, Rakithan Murugesu, Odile Gaisl, Nimmy Varghese, Anne Eckert, Mirjam Christ-Crain

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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.

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精氨酸加压素缺乏症（中枢性糖尿病）患者和健康对照组血浆催产素水平对胰高血糖素的反应。

目的：最近，我们使用3,4-亚甲二氧基甲基苯丙胺（MDMA）作为一种新型激发试验，证实了精氨酸血管加压素（AVP）缺乏症（中枢性糖尿病）患者中存在额外的催产素（OT）缺乏症。然而，MDMA 激起试验对临床实践的影响可能具有挑战性。胰高血糖素能有效刺激血管加压素能神经元，使血浆中的 copeptin 大量增加。因此，我们假设这种激惹试验也可能刺激 OT：这是瑞士巴塞尔大学医院一项前瞻性双盲、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 名性别和体重指数相匹配的健康参与者。每位参与者都接受了胰高血糖素试验（静脉注射 1 毫克胰高血糖素）和安慰剂试验（静脉注射 0.9% 生理盐水）。分别在基线、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会刺激 OT，以及 AVP 缺乏症患者和健康参与者的 OT 水平是否存在差异。采用线性混合效应模型对主要结果（180 分钟内 OT 的最大变化）进行组间和条件间比较：结果：在健康参与者中，基线 OT 中位数为 82.7 pg/ml [62.3-94.3]，注射胰高血糖素后略有增加，最大值为 93.3 pg/ml [87.2-121.1]，变化幅度为 24.9 pg/ml [5.1-27.8]。同样，在 AVP 缺乏症患者中，基线时的 OT 中位数为 73.9 pg/ml [65.3-81.6]，注射胰高血糖素后略有增加，达到 114.9 pg/ml [70.9-140.9]，导致变化增加 36.8 pg/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：-0.5 pg/ml；95%-CI [-25，24]；p = 0.97），与健康参与者相比，患者与治疗组之间没有显著的交互作用（交互作用：28 pg/ml；95%-CI [-7，62]；p = 0.13）：我们发现胰高血糖素对血浆 OT 水平没有影响，AVP 缺乏症患者与健康参与者之间也没有差异。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.