Cited by 369Diabetes, Cardiovascular Risks, and LipoproteinsGenetic Associations and EpidemiologyCardiovascular Function and Risk Factors

Type 2 diabetes mellitus and cardiovascular disease: Genetic and epigenetic links

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De Rosa, Salvatore, Arcidiacono, Biagio, Chiefari, Eusebio, Brunetti, Antonio, Indolfi, Ciro, Foti, Daniela P.·2018·Frontiers in Endocrinology

Abstract

Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.

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  • HMGA1 is a master regulator of the vascular SMC phenotypic switch following vessel wall injury and release of proinflammatory cytokines.

    “The architectural transcription factor HMGA1 is a master regulator of the vascular SMCs phenotypic switch that follows vessel wall injury and release of proinflammatory cytokines [6,190,191].”

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  1. [37]Ashar FN Arking DE Genomics of complex cardiovascular disease. 2nd ed In: Kumar D Eng C, editors. Genomic Medicine: Principles and Practice. New York, NY: Oxford University Press (2014). p. 316– 36.

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Authors
De Rosa, S., Arcidiacono, B., Chiefari, E., Brunetti, A., Indolfi, C., & Foti, D. P.
Affiliations
Magna Graecia University (IT)
Corresponding author
  • Brunetti, Antonio
  • Indolfi, Ciro
  • Foti, Daniela P.
Venue
Frontiers in Endocrinology
Published
2018-01-17
Volume
9
Pages
2-2
ISSN
1664-2392 (ISSN-L)
OpenAlex
W2783270596
Cited by
369
References
199
Citations by year
2026: 20 · 2025: 44 · 2024: 50 · 2023: 56 · 2022: 46 · 2021: 46 · 2020: 42 · 2019: 42 · 2018: 23
FWCI
5.88
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
type 2 diabetes, cardiovascular disease, diabetic cardiomyopathy, atherosclerosis, heart failure, genetic susceptibility, epigenetics, microRNA, long non-coding RNA, hyperglycemia, hyperinsulinemia, insulin resistance, obesity, inflammation, thrombophilia, extracellular matrix remodeling, redox state

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