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二甲双胍是否会影响类固醇激素和自闭症特征?一项试点研究的初步见解。

Are steroid hormones and autistic traits affected by metformin? First insights from a pilot.

作者信息

Gasser Benedikt, Escher Genevieve, Calin Anca-Elena, Deppeler Michael, Marchon Miriam, Kurz Johann, Mohaupt Markus

机构信息

Department of Sport, Exercise and Health, Division Sport and Exercise Medicine, University of Basel, Grosse Allee 6, CH-4052, Basel, Switzerland.

Lindenhofgruppe, Teaching Hospital of Internal Medicine, Lindenhofgruppe, 3006, Berne, Switzerland.

出版信息

Compr Psychoneuroendocrinol. 2023 Jul 29;16:100196. doi: 10.1016/j.cpnec.2023.100196. eCollection 2023 Nov.

DOI:10.1016/j.cpnec.2023.100196
PMID:37577184
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10415721/
Abstract

BACKGROUND

Different lines of evidence imply that metformin could alter steroid hormone homeostasis and thereby improve social impairment. Here, we tried to correlate the impact of metformin treatment on alterations in steroid hormones and autism spectrum traits before versus after treatment with metformin.

MATERIAL & METHODS: Urine steroid hormones were measured using gas chromatography mass spectrometry in 12 male subjects (54.2 ± 9.1 years, 177.3 ± 4.1 cm, 80 ± 10.4 kg) and 7 female subjects (64.14 ± 18.0 years, 162.7 ± 4.1 cm, 76.1 ± 10.4 kg). Furthermore, a questionnaire on autism spectrum traits (Autism Spectrum Questionnaire]) was administered prior to and after metformin treatment.

RESULTS

Overall, a decrease of steroid hormones were detected, which were most pronounced in the metabolites of corticosterone, deoxycortisol, cortisol, as well as androgens. These remained after Bonferroni correction (three classes: glucocorticoid, mineralocorticoid, androgens). No effect on autism spectrum traits (social skills, attention switching skills, attention to detail skills, communication skills, imagination skills), was identified pre versus post metformin treatment.

DISCUSSION

The decreased steroid hormone levels are based on different mechanisms; one effect is likely via mitochondria, another effect via activated protein kinase prior to post treatment. The finding on autistic traits must be taxed as negative and do not directly provide an argument for using metformin in the treatment of autism.

摘要

背景

不同的证据表明二甲双胍可能会改变甾体激素稳态,从而改善社交障碍。在此,我们试图将二甲双胍治疗对甾体激素变化的影响与治疗前后的自闭症谱系特征进行关联。

材料与方法

使用气相色谱 - 质谱法对12名男性受试者(年龄54.2 ± 9.1岁,身高177.3 ± 4.1厘米,体重80 ± 10.4千克)和7名女性受试者(年龄64.14 ± 18.0岁,身高162.7 ± 4.1厘米,体重76.1 ± 10.4千克)的尿液甾体激素进行测量。此外,在二甲双胍治疗前后发放了一份关于自闭症谱系特征的问卷(自闭症谱系问卷)。

结果

总体而言,检测到甾体激素有所下降,在皮质酮、脱氧皮质醇、皮质醇以及雄激素的代谢产物中最为明显。经Bonferroni校正后(三类:糖皮质激素、盐皮质激素、雄激素)这些结果仍然成立。未发现二甲双胍治疗前后对自闭症谱系特征(社交技能、注意力转换技能、细节关注技能、沟通技能、想象力技能)有影响。

讨论

甾体激素水平下降基于不同机制;一种影响可能通过线粒体,另一种影响可能通过治疗前后激活的蛋白激酶。关于自闭症特征的这一发现必须被视为负面结果,并且不能直接为使用二甲双胍治疗自闭症提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d809/10415721/d650a7b1d033/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d809/10415721/51c2aa85c591/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d809/10415721/5953769b67f2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d809/10415721/d650a7b1d033/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d809/10415721/51c2aa85c591/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d809/10415721/5953769b67f2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d809/10415721/d650a7b1d033/gr3.jpg

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本文引用的文献

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2
Metformin-Treatment Option for Social Impairment? An Open Clinical Trial to Elucidate the Effects of Metformin Treatment on Steroid Hormones and Social Behavior.二甲双胍——治疗社交障碍的选择?一项阐明二甲双胍治疗对类固醇激素和社交行为影响的开放性临床试验。
Life (Basel). 2022 Jul 5;12(7):998. doi: 10.3390/life12070998.
3
How Is CYP17A1 Activity Altered in Autism? A Pilot Study to Identify Potential Pharmacological Targets.
自闭症中CYP17A1活性如何改变?一项确定潜在药理学靶点的初步研究。
Life (Basel). 2022 Jun 10;12(6):867. doi: 10.3390/life12060867.
4
Effect of Metformin on Testosterone Levels in Male Patients With Type 2 Diabetes Mellitus Treated With Insulin.二甲双胍对胰岛素治疗的 2 型糖尿病男性患者睾酮水平的影响。
Front Endocrinol (Lausanne). 2021 Dec 24;12:813067. doi: 10.3389/fendo.2021.813067. eCollection 2021.
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Effect of Metformin on Anthropometric Measurements and Hormonal and Biochemical Profile in Patients with Prediabetes.二甲双胍对糖尿病前期患者人体测量学指标及激素和生化谱的影响。
J Diabetes Res. 2021 Dec 14;2021:8275303. doi: 10.1155/2021/8275303. eCollection 2021.
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