Circulating small non‐coding RNAs are associated with the insulin‐resistant and obesity‐related type 2 diabetes clusters
Diabetes Obesity and Metabolism, vol. 26, pp. 4375–4385
Abstract
AIM: To uncover differences in small non-coding RNAs (sncRNAs) in individuals with type 2 diabetes (T2D) categorized into five clusters based on individual characteristics, which may aid in the identification of those prone to rapid progression. MATERIALS AND METHODS: In the Hoorn Diabetes Care System (DCS) cohort, participants were clustered by age, body mass index (BMI), and glycated haemoglobin, C-peptide and high-density lipoprotein (HDL) cholesterol levels, yielding severe insulin-deficient diabetes, severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), mild diabetes, and mild diabetes with high HDL cholesterol clusters (n = 412). Utilizing plasma sncRNA-sequencing, we identified distinct cluster-specific sncRNAs. Validation was performed in a smaller DCS Hoorn dataset (n = 138). To elucidate their potential functions, we examined tissue expression, identified potential targets or (co-)regulated proteins, conducted gene set enrichment analyses on the targets through Reactome, and examined tissue expression of the (co-)regulated proteins. RESULTS: The insulin-resistant cluster exhibited aberrant expression of 10 sncRNAs, while the high BMI cluster featured eight differentially expressed sncRNAs. Multiple (co-)regulated proteins were identified for sncRNAs associated with both clusters. Proteins associated with both clusters showed enrichment for metabolism. Proteins that specifically and only associated with the SIRD cluster showed enrichment for immune-related signalling. Furthermore, MOD cluster-specific associated proteins showed enrichment for the complement system. CONCLUSIONS: Our research showed differential sncRNA levels among type 2 diabetes clusters. This may reflect and could deepen our understanding of molecular mechanisms, in development, progression, and risk factors for each cluster.
Authors 7
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Juliette A. de Klerk Aachen Department of Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands Department of Internal Medicine Division of Nephrology Leiden University Medical Center Leiden The Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands
Department of Internal Medicine, Division of Nephrology Leiden University Medical Center Leiden The Netherlands
Einthoven Laboratory for Vascular and Regenerative Medicine Leiden University Medical Center Leiden The Netherlands
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Amsterdam Public Health · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Public Health Institute Amsterdam UMC Amsterdam the Netherlands
Department of Epidemiology and Data Science Amsterdam UMC, location Vrije Universiteit Amsterdam the Netherlands
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Roel Bijkerk Aachen Department of Internal Medicine Division of Nephrology Leiden University Medical Center Leiden The Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Division of Nephrology Leiden University Medical Center Leiden The Netherlands
Einthoven Laboratory for Vascular and Regenerative Medicine Leiden University Medical Center Leiden The Netherlands
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Anton Jan van Zonneveld Aachen Department of Internal Medicine Division of Nephrology Leiden University Medical Center Leiden The Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Division of Nephrology Leiden University Medical Center Leiden The Netherlands
Einthoven Laboratory for Vascular and Regenerative Medicine Leiden University Medical Center Leiden The Netherlands
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Amsterdam Public Health · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Public Health Institute Amsterdam UMC Amsterdam the Netherlands
Department of General Practice and Elderly Care Medicine Amsterdam Public Health Research Institute, Amsterdam UMC, location VUmc Amsterdam the Netherlands
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Leen M. ‘t Hart Aachen Department of Biomedical Data Sciences Section Molecular Epidemiology Leiden University Medical Center Leiden the Netherlands Department of Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands
Leiden University Medical Center · Amsterdam Public Health · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Public Health Institute Amsterdam UMC Amsterdam the Netherlands
Department of Biomedical Data Sciences, Section Molecular Epidemiology Leiden University Medical Center Leiden the Netherlands
Department of Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands
Department of Epidemiology and Data Science Amsterdam UMC, location Vrije Universiteit Amsterdam the Netherlands
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Roderick C. Slieker corresponding Aachen Department of Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands
Leiden University Medical Center · Amsterdam Public Health · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Public Health Institute Amsterdam UMC Amsterdam the Netherlands
Department of Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands
Department of Epidemiology and Data Science Amsterdam UMC, location Vrije Universiteit Amsterdam the Netherlands
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