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1型糖尿病患儿的线粒体衍生肽-c水平能否作为早期糖尿病肾病的指标?

Could MOTS-c Levels in Children with Type 1 Diabetes Mellitus Be an Indicator for Early Diabetic Kidney Disease?

作者信息

Girişgen İlknur, Altıncık Selda Ayça, Avcı Esin, Öcal Murat, Becerir Tülay, Malaş Öztekin Gaye, Özhan Bayram, Yüksel Selçuk

机构信息

Pamukkale University Faculty of Medicine, Department of Pediatric Nephrology, Denizli, Türkiye

Pamukkale University Faculty of Medicine, Department of Pediatric Endocrinology, Denizli, Türkiye

出版信息

J Clin Res Pediatr Endocrinol. 2025 May 27;17(2):168-175. doi: 10.4274/jcrpe.galenos.2024.2024-5-6. Epub 2024 Dec 23.

DOI:10.4274/jcrpe.galenos.2024.2024-5-6
PMID:39711006
Abstract

OBJECTIVE

To compare serum mitochondrial open reading frame of 12S rRNA-c (MOTS-c) levels, a new potential biomarker for oxidative stress, in children with type 1 diabetes mellitus (T1DM) and healthy children. A further aim was to investigate serum MOTS-c levels as a potential early indicator of diabetic kidney disease (DKD) by correlating levels with changes in glomerular filtration and microalbuminuria.

METHODS

Patients with a diagnosis of T1DM and healthy controls were recruited. MOTS-c, urinary albumin excretion, estimated glomerular filtration rate (eGFR), and hemoglobin A1c (HbA1c) were evaluated and clinical features and anthropometric measurements were collected. Patients were stratified according to diabetes duration, presence of albuminuria, glomerular hyperfiltration, eGFR decline and metabolic control.

RESULTS

The T1DM group included 82 [female:male (F:M) 1:1.64] patients while the controls numbered 61 (F:M 1:0.97), with respective mean ages of 14.3±3.3 and 10.6±4.2 years (p<0.01). MOTS-c levels were significantly lower in the T1DM group than controls (76.2±1.3 vs 105.2±7.0, p<0.001). No difference was found in MOTS-c levels between patient subgroups categorized by diabetes duration, obesity, metabolic control, hypertension, hyperlipidemia, glomerular hyperfiltration, decline in eGFR, and presence of microalbuminuria. Simple linear regression indicated that MOTS-c was not predictive for DKD.

CONCLUSION

MOTS-c levels were lower in children with T1DM than in healthy children. However, the lack of association of MOTS-c with renal biomarkers suggested that it is not an effective early marker for DKD. However, this finding suggests that the onset of oxidative damage and mitochondrial dysfunction in T1DM is independent of DKD. In addition, the results suggests that HbA1c and duration of diabetes are significant risk factors for development of microalbuminuria, while changes in eGFR and microalbuminuria continue to serve as indicators of DKD.

摘要

目的

比较1型糖尿病(T1DM)患儿与健康儿童血清中线粒体12S rRNA - c开放阅读框(MOTS - c)水平,MOTS - c是一种新的氧化应激潜在生物标志物。另一目的是通过将血清MOTS - c水平与肾小球滤过及微量白蛋白尿的变化相关联,研究其作为糖尿病肾病(DKD)潜在早期指标的可能性。

方法

招募T1DM诊断患者及健康对照。评估MOTS - c、尿白蛋白排泄、估计肾小球滤过率(eGFR)和糖化血红蛋白(HbA1c),并收集临床特征和人体测量数据。根据糖尿病病程、蛋白尿情况、肾小球高滤过、eGFR下降及代谢控制情况对患者进行分层。

结果

T1DM组包括82例患者[女性:男性(F:M)为1:1.64],对照组有61例(F:M为1:0.97),平均年龄分别为14.3±3.3岁和10.6±4.2岁(p<0.01)。T1DM组的MOTS - c水平显著低于对照组(76.2±1.3 vs 105.2±7.0,p<0.001)。按糖尿病病程、肥胖、代谢控制、高血压、高脂血症、肾小球高滤过、eGFR下降及微量白蛋白尿情况分类的患者亚组之间,MOTS - c水平未发现差异。简单线性回归表明,MOTS - c不能预测DKD。

结论

T1DM患儿的MOTS - c水平低于健康儿童。然而,MOTS - c与肾脏生物标志物缺乏关联表明它不是DKD的有效早期标志物。不过,这一发现提示T1DM中氧化损伤和线粒体功能障碍的发生独立于DKD。此外,结果表明HbA1c和糖尿病病程是微量白蛋白尿发生的重要危险因素,而eGFR和微量白蛋白尿的变化仍是DKD的指标。

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本文引用的文献

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Diabetes Metab Syndr Obes. 2023 Apr 12;16:1013-1020. doi: 10.2147/DMSO.S403934. eCollection 2023.
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Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases.线粒体编码肽 MOTS-c、糖尿病与衰老相关疾病。
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MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases.MOTS-c:人类衰老及衰老相关疾病中最新的线粒体衍生肽。
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Mitochondrial-Derived Peptides in Diabetes and Its Complications.糖尿病及其并发症中的线粒体衍生肽。
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Diabetic kidney disease in children and adolescents: an update.儿童和青少年糖尿病肾病:最新进展。
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Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.线粒体编码的 MOTS-c 可防止自身免疫性糖尿病中胰岛破坏。
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