A non-invasive method for screening mitochondrial diabetes

BackgroundMitochondrial diabetes mellitus (MDM) is a special type of diabetes resulting from functional defects in mitochondria. Its incidence rate is low, and it can often be misdiagnosed as either type 1 or type 2 diabetes in clinical settings. Due to limited clinical experience in diagnosing and...

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Main Authors: Hangyu Fang, Xiaoe Li, Shuping Wang, Mei Zhang, Victor Wei Zhang, Chao Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1536331/full
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author Hangyu Fang
Hangyu Fang
Xiaoe Li
Shuping Wang
Mei Zhang
Victor Wei Zhang
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
author_facet Hangyu Fang
Hangyu Fang
Xiaoe Li
Shuping Wang
Mei Zhang
Victor Wei Zhang
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
author_sort Hangyu Fang
collection DOAJ
description BackgroundMitochondrial diabetes mellitus (MDM) is a special type of diabetes resulting from functional defects in mitochondria. Its incidence rate is low, and it can often be misdiagnosed as either type 1 or type 2 diabetes in clinical settings. Due to limited clinical experience in diagnosing and treating MDM, the rate of missed diagnosis is high. Therefore, employing appropriate detection methods for the rapid screening of suspected MDM patients can facilitate early diagnosis of MDM.MethodsWe conducted a multicenter observational study by collecting oral exfoliated cells from patients and detecting the m.3243A>G mutation using Polymerase Chain Reaction (PCR). We estimated the positivity rate of MDM and clinically evaluated the detection method through clinical trials. Additionally, we summarized the clinical phenotypes of patients who tested positive and compared the clinical manifestations between MDM and non-MDM patients using statistical analysis, providing a diagnostic foundation for clinicians.ResultsWe collected data from a total of 478 patients and identified 16 cases of m.3243A>G mutation-positive patients by collecting oral exfoliated cell samples for PCR testing, yielding a positivity rate of 3.35% and an asymptomatic carrier rate of 0.84%. These results are slightly higher than those reported in previous research. The gene mutation detection method demonstrated high credibility and was non-invasive, with a clinical sensitivity of 87.2% and clinical specificity of 96.9%. Additionally, patient satisfaction was high in this study. Statistical analysis revealed a significant difference in clinical manifestations between MDM and non-MDM patients. MDM patients were more likely to experience neurological hearing loss and multiple systemic manifestations, and their condition was consistent with maternal inheritance, in line with previous research findings.ConclusionThe detection of the m.3243A>G mutation through the collection of oral exfoliated cells offers several advantages over other methods, including simplicity, non-invasiveness, and high specificity and sensitivity. However, it is currently underutilized. Therefore, further experiments are needed to study and validate this approach in order to optimize MDM screening methods and improve diagnostic rates for MDM.
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spelling doaj-art-933cbf05c9a640bdaf9014b7e57e13712025-08-20T02:44:16ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-05-011610.3389/fgene.2025.15363311536331A non-invasive method for screening mitochondrial diabetesHangyu Fang0Hangyu Fang1Xiaoe Li2Shuping Wang3Mei Zhang4Victor Wei Zhang5Chao Xu6Chao Xu7Chao Xu8Chao Xu9Chao Xu10Chao Xu11Chao Xu12Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaKey Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, ChinaDepartment of Endocrinology, Weishan County People’s Hospital, Jining, Shandong, ChinaDepartment of Endocrinology and Metabolism, Dongying People’s Hospital, Dongying, Shandong, ChinaAffiliated Hospital of Jining Medical University, Jining, Shandong, ChinaDepartment of Genomic Medicine, AmCare Genomics Lab, Guangzhou, Guangdong Province, ChinaDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaKey Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, ChinaShandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, ChinaShandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China“Chuangxin China” Innovation Base of Stem Cell and Gene Therapy for Endocrine Metabolic Diseases, Jinan, Shandong, China0Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China1Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, ChinaBackgroundMitochondrial diabetes mellitus (MDM) is a special type of diabetes resulting from functional defects in mitochondria. Its incidence rate is low, and it can often be misdiagnosed as either type 1 or type 2 diabetes in clinical settings. Due to limited clinical experience in diagnosing and treating MDM, the rate of missed diagnosis is high. Therefore, employing appropriate detection methods for the rapid screening of suspected MDM patients can facilitate early diagnosis of MDM.MethodsWe conducted a multicenter observational study by collecting oral exfoliated cells from patients and detecting the m.3243A>G mutation using Polymerase Chain Reaction (PCR). We estimated the positivity rate of MDM and clinically evaluated the detection method through clinical trials. Additionally, we summarized the clinical phenotypes of patients who tested positive and compared the clinical manifestations between MDM and non-MDM patients using statistical analysis, providing a diagnostic foundation for clinicians.ResultsWe collected data from a total of 478 patients and identified 16 cases of m.3243A>G mutation-positive patients by collecting oral exfoliated cell samples for PCR testing, yielding a positivity rate of 3.35% and an asymptomatic carrier rate of 0.84%. These results are slightly higher than those reported in previous research. The gene mutation detection method demonstrated high credibility and was non-invasive, with a clinical sensitivity of 87.2% and clinical specificity of 96.9%. Additionally, patient satisfaction was high in this study. Statistical analysis revealed a significant difference in clinical manifestations between MDM and non-MDM patients. MDM patients were more likely to experience neurological hearing loss and multiple systemic manifestations, and their condition was consistent with maternal inheritance, in line with previous research findings.ConclusionThe detection of the m.3243A>G mutation through the collection of oral exfoliated cells offers several advantages over other methods, including simplicity, non-invasiveness, and high specificity and sensitivity. However, it is currently underutilized. Therefore, further experiments are needed to study and validate this approach in order to optimize MDM screening methods and improve diagnostic rates for MDM.https://www.frontiersin.org/articles/10.3389/fgene.2025.1536331/fullmitochondrial diabetes mellitusm.3243A>Gmutationsscreeningnon-invasive
spellingShingle Hangyu Fang
Hangyu Fang
Xiaoe Li
Shuping Wang
Mei Zhang
Victor Wei Zhang
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
Chao Xu
A non-invasive method for screening mitochondrial diabetes
Frontiers in Genetics
mitochondrial diabetes mellitus
m.3243A>G
mutations
screening
non-invasive
title A non-invasive method for screening mitochondrial diabetes
title_full A non-invasive method for screening mitochondrial diabetes
title_fullStr A non-invasive method for screening mitochondrial diabetes
title_full_unstemmed A non-invasive method for screening mitochondrial diabetes
title_short A non-invasive method for screening mitochondrial diabetes
title_sort non invasive method for screening mitochondrial diabetes
topic mitochondrial diabetes mellitus
m.3243A>G
mutations
screening
non-invasive
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1536331/full
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