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Changes in Splicing Machinery Components Influence, Precede, and Early Predict the Development of Type 2 Diabetes:

Manuel D Gahete1, Mercedes Del Rio-Moreno1, Antonio Camargo2

  • 1Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.; Universidad de Córdoba, Córdoba, Spain.; Reina Sofia University Hospital, Córdoba, Spain.; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain.

Ebiomedicine
|November 18, 2018
PubMed
Abstract

Insights

Alterations in splicing machinery components precede and predict Type-2 diabetes mellitus (T2DM) development in cardiovascular disease patients. These changes in gene expression offer a new risk assessment tool for T2DM.

Area of Science:

  • Molecular biology
  • Genetics
  • Endocrinology

Background:

  • Type-2 diabetes mellitus (T2DM) is a growing global health concern, significantly increasing cardiovascular disease risk.
  • Aberrant gene expression and splicing are linked to T2DM, suggesting a role for splicing machinery dysregulation.

Purpose of the Study:

  • To investigate if splicing machinery dysregulations precede, contribute to, and predict T2DM development.
  • To analyze splicing machinery component expression in patients with cardiovascular disease.

Main Methods:

  • Studied 215 patients with cardiovascular disease, assessing splicing machinery component expression in peripheral blood mononuclear cells (PBMCs).
  • Compared baseline fasting and postprandial PBMCs from patients who developed T2DM (n=107) versus those who did not (n=108) over 5 years.
  • In vitro analysis of PBMC splicing machinery expression using serum from T2DM patients.

Main Results:

  • Markedly altered expression of key splicing machinery components (e.g., RNU2, RNU4, RNU12) in incident T2DM patients' PBMCs.
  • Serum from incident T2DM patients reduced splicing machinery component expression in healthy PBMCs.
  • Fasting/postprandial splicing machinery component levels in PBMCs predicted T2DM risk (OR > 4) and development (AUC > 0.85).

Conclusions:

  • Splicing machinery alterations are present before and can predict T2DM development in cardiovascular disease patients.
  • These findings highlight splicing machinery as a potential biomarker for T2DM risk assessment.
Keywords:
OGTTPeripheral blood mononuclear cells (PBMCs)Postprandial stateRNUsSpliceosome

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