JACC Focus Seminar: Obesity, Diabetes, And Phenotypes
JACC Focus Seminar
Molecular Aspects of Lifestyle and Environmental Effects in Patients With Diabetes: JACC Focus Seminar

https://doi.org/10.1016/j.jacc.2021.02.070Get rights and content
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Highlights

  • T2D results from metabolic dysfunction involving diverse organ systems and biological processes.

  • Integration of metabolomic profiles from clinical and mechanistic studies will enhance understanding of T2D.

  • Molecular profiling may be used to assess risk, disease stage, and treatment responses in patients with T2D.

Abstract

Diabetes is characterized as an integrated condition of dysregulated metabolism across multiple tissues, with well-established consequences on the cardiovascular system. Recent advances in precision phenotyping in biofluids and tissues in large human observational and interventional studies have afforded a unique opportunity to translate seminal findings in models and cellular systems to patients at risk for diabetes and its complications. Specifically, techniques to assay metabolites, proteins, and transcripts, alongside more recent assessment of the gut microbiome, underscore the complexity of diabetes in patients, suggesting avenues for precision phenotyping of risk, response to intervention, and potentially novel therapies. In addition, the influence of external factors and inputs (eg, activity, diet, medical therapies) on each domain of molecular characterization has gained prominence toward better understanding their role in prevention. Here, the authors provide a broad overview of the role of several of these molecular domains in human translational investigation in diabetes.

Key Words

cardiovascular risk
diabetes
metabolism

Abbreviations and Acronyms

AMPK
5′ adenosine monophosphate–activated protein kinase
BCAA
branched-chain amino acid
CVD
cardiovascular disease
DMGV
dimethylguanidino valeric acid
GF
germ-free
IL
interleukin
IR
insulin resistance
miRNA
micro–ribonucleic acid
RNA
ribonucleic acid
SCFA
short-chain fatty acid
SGLT2
sodium-glucose cotransporter–2
T2D
type 2 diabetes mellitus

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Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

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