Characterizing Circulating microRNA Signatures of Type 2 Diabetes Subtypes

Type 2 diabetes (T2D) is a heterogeneous disease influenced by both genetic and environmental factors. Recent studies suggest that T2D subtypes may exhibit distinct gene expression profiles. In this study, we aimed to identify T2D cluster-specific miRNA expression signatures for the previously repor...

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Published inInternational journal of molecular sciences Vol. 26; no. 2; p. 637
Main Authors Sulaiman, Fatima, Khyriem, Costerwell, Dsouza, Stafny, Abdul, Fatima, Alkhnbashi, Omer, Faraji, Hanan, Farooqi, Muhammad, Al Awadi, Fatheya, Hassanein, Mohammed, Ahmed, Fayha, Alsharhan, Mouza, Tawfik, Abdel Rahman, Khamis, Amar Hassan, Bayoumi, Riad
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 14.01.2025
MDPI
Subjects
Adult
Aged
Analysis
Biomarkers - blood
Body mass index
Case-Control Studies
Circulating MicroRNA - blood
Circulating MicroRNA - genetics
Cluster analysis
Computational Biology - methods
Diabetes
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - classification
Diabetes Mellitus, Type 2 - genetics
Disease
DNA methylation
Drugs
Epigenetics
Expatriates
Fasting
Female
Gene expression
Gene Expression Profiling
Genes
Genomes
Glucose
Humans
Insulin
Insulin resistance
Insulin Resistance - genetics
Male
Metabolism
MicroRNA
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
Pathophysiology
Patients
RNA sequencing
Transcriptome
Type 2 diabetes
United Arab Emirates
Middle East
Type 2 diabetes
T2D subtypes
insulin resistance
circulating microRNA
pathophysiology
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms26020637

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Abstract Type 2 diabetes (T2D) is a heterogeneous disease influenced by both genetic and environmental factors. Recent studies suggest that T2D subtypes may exhibit distinct gene expression profiles. In this study, we aimed to identify T2D cluster-specific miRNA expression signatures for the previously reported five clinical subtypes that characterize the underlying pathophysiology of long-standing T2D: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and mild early-onset diabetes (MEOD). We analyzed the circulating microRNAs (miRNAs) in 45 subjects representing the five T2D clusters and 7 non-T2D healthy controls by single-end small RNA sequencing. Bioinformatic analyses identified a total of 430 known circulating miRNAs and 13 previously unreported novel miRNAs. Of these, 71 were upregulated and 37 were downregulated in either controls or individual clusters. Each T2D subtype was associated with a specific dysregulated miRNA profile, distinct from that of healthy controls. Specifically, 3 upregulated miRNAs were unique to SIRD, 1 to MARD, 9 to MOD, and 18 to MEOD. Among the downregulated miRNAs, 11 were specific to SIRD, 9 to SIDD, 2 to MARD, and 1 to MEOD. Our study confirms the heterogeneity of T2D, represented by distinguishable subtypes both clinically and epigenetically and highlights the potential of miRNAs as markers for distinguishing the pathophysiology of T2D subtypes.
AbstractList Type 2 diabetes (T2D) is a heterogeneous disease influenced by both genetic and environmental factors. Recent studies suggest that T2D subtypes may exhibit distinct gene expression profiles. In this study, we aimed to identify T2D cluster-specific miRNA expression signatures for the previously reported five clinical subtypes that characterize the underlying pathophysiology of long-standing T2D: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and mild early-onset diabetes (MEOD). We analyzed the circulating microRNAs (miRNAs) in 45 subjects representing the five T2D clusters and 7 non-T2D healthy controls by single-end small RNA sequencing. Bioinformatic analyses identified a total of 430 known circulating miRNAs and 13 previously unreported novel miRNAs. Of these, 71 were upregulated and 37 were downregulated in either controls or individual clusters. Each T2D subtype was associated with a specific dysregulated miRNA profile, distinct from that of healthy controls. Specifically, 3 upregulated miRNAs were unique to SIRD, 1 to MARD, 9 to MOD, and 18 to MEOD. Among the downregulated miRNAs, 11 were specific to SIRD, 9 to SIDD, 2 to MARD, and 1 to MEOD. Our study confirms the heterogeneity of T2D, represented by distinguishable subtypes both clinically and epigenetically and highlights the potential of miRNAs as markers for distinguishing the pathophysiology of T2D subtypes.Type 2 diabetes (T2D) is a heterogeneous disease influenced by both genetic and environmental factors. Recent studies suggest that T2D subtypes may exhibit distinct gene expression profiles. In this study, we aimed to identify T2D cluster-specific miRNA expression signatures for the previously reported five clinical subtypes that characterize the underlying pathophysiology of long-standing T2D: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and mild early-onset diabetes (MEOD). We analyzed the circulating microRNAs (miRNAs) in 45 subjects representing the five T2D clusters and 7 non-T2D healthy controls by single-end small RNA sequencing. Bioinformatic analyses identified a total of 430 known circulating miRNAs and 13 previously unreported novel miRNAs. Of these, 71 were upregulated and 37 were downregulated in either controls or individual clusters. Each T2D subtype was associated with a specific dysregulated miRNA profile, distinct from that of healthy controls. Specifically, 3 upregulated miRNAs were unique to SIRD, 1 to MARD, 9 to MOD, and 18 to MEOD. Among the downregulated miRNAs, 11 were specific to SIRD, 9 to SIDD, 2 to MARD, and 1 to MEOD. Our study confirms the heterogeneity of T2D, represented by distinguishable subtypes both clinically and epigenetically and highlights the potential of miRNAs as markers for distinguishing the pathophysiology of T2D subtypes.
Type 2 diabetes (T2D) is a heterogeneous disease influenced by both genetic and environmental factors. Recent studies suggest that T2D subtypes may exhibit distinct gene expression profiles. In this study, we aimed to identify T2D cluster-specific miRNA expression signatures for the previously reported five clinical subtypes that characterize the underlying pathophysiology of long-standing T2D: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and mild early-onset diabetes (MEOD). We analyzed the circulating microRNAs (miRNAs) in 45 subjects representing the five T2D clusters and 7 non-T2D healthy controls by single-end small RNA sequencing. Bioinformatic analyses identified a total of 430 known circulating miRNAs and 13 previously unreported novel miRNAs. Of these, 71 were upregulated and 37 were downregulated in either controls or individual clusters. Each T2D subtype was associated with a specific dysregulated miRNA profile, distinct from that of healthy controls. Specifically, 3 upregulated miRNAs were unique to SIRD, 1 to MARD, 9 to MOD, and 18 to MEOD. Among the downregulated miRNAs, 11 were specific to SIRD, 9 to SIDD, 2 to MARD, and 1 to MEOD. Our study confirms the heterogeneity of T2D, represented by distinguishable subtypes both clinically and epigenetically and highlights the potential of miRNAs as markers for distinguishing the pathophysiology of T2D subtypes.
Audience Academic
Author Alsharhan, Mouza
Al Awadi, Fatheya
Farooqi, Muhammad
Tawfik, Abdel Rahman
Dsouza, Stafny
Ahmed, Fayha
Alkhnbashi, Omer
Abdul, Fatima
Faraji, Hanan
Bayoumi, Riad
Hassanein, Mohammed
Khyriem, Costerwell
Sulaiman, Fatima
Khamis, Amar Hassan
AuthorAffiliation 2 Center for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates; omer.alkhnbashi@dubaihealth.ae
6 Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates; abdel.tawfik@dubaihealth.ae (A.R.T.); amar.hassan@dubaihealth.ae (A.H.K.)
1 College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates; fatima.sulaiman@students.mbru.ac.ae (F.S.); costerwell.khyriem@dubaihealth.ae (C.K.); stafny.dsouza@dubaihealth.ae (S.D.); fatima.abdul@dubaihealth.ae (F.A.); hanan.faraji@students.mbru.ac.ae (H.F.)
5 Pathology Department, Dubai Hospital, Dubai Health, Dubai P.O. Box 7272, United Arab Emirates; faaahmed@dubaihealth.ae (F.A.); maalsharhan@dubaihealth.ae (M.A.)
3 Dubai Diabetes Center, Dubai Health, Dubai P.O. Box 7272, United Arab Emirates; mhfaro
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– name: 1 College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates; fatima.sulaiman@students.mbru.ac.ae (F.S.); costerwell.khyriem@dubaihealth.ae (C.K.); stafny.dsouza@dubaihealth.ae (S.D.); fatima.abdul@dubaihealth.ae (F.A.); hanan.faraji@students.mbru.ac.ae (H.F.)
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– name: 6 Hamdan Bin Mohammed College of Dental Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates; abdel.tawfik@dubaihealth.ae (A.R.T.); amar.hassan@dubaihealth.ae (A.H.K.)
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Keywords Type 2 diabetes
T2D subtypes
insulin resistance
circulating microRNA
pathophysiology
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SSID ssj0023259
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Snippet Type 2 diabetes (T2D) is a heterogeneous disease influenced by both genetic and environmental factors. Recent studies suggest that T2D subtypes may exhibit...
SourceID pubmedcentral
proquest
gale
pubmed
crossref
SourceType Open Access Repository
Aggregation Database
Index Database
StartPage 637
SubjectTerms Adult
Aged
Analysis
Biomarkers - blood
Body mass index
Case-Control Studies
Circulating MicroRNA - blood
Circulating MicroRNA - genetics
Cluster analysis
Computational Biology - methods
Diabetes
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - classification
Diabetes Mellitus, Type 2 - genetics
Disease
DNA methylation
Drugs
Epigenetics
Expatriates
Fasting
Female
Gene expression
Gene Expression Profiling
Genes
Genomes
Glucose
Humans
Insulin
Insulin resistance
Insulin Resistance - genetics
Male
Metabolism
MicroRNA
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
Pathophysiology
Patients
RNA sequencing
Transcriptome
Type 2 diabetes
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Title Characterizing Circulating microRNA Signatures of Type 2 Diabetes Subtypes
URI https://www.ncbi.nlm.nih.gov/pubmed/39859351
https://www.proquest.com/docview/3159500179
https://www.proquest.com/docview/3159801281
https://pubmed.ncbi.nlm.nih.gov/PMC11766090
Volume 26
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