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Diabetes. 2017 Feb;66(2):347-357. doi: 10.2337/db16-0731. Epub 2016 Nov 29.

Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes.

Author information

1
King's British Heart Foundation Centre, King's College London, London, U.K. peter.willeit@i-med.ac.at manuel.mayr@kcl.ac.uk.
2
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
3
Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
4
King's British Heart Foundation Centre, King's College London, London, U.K.
5
Department of Internal Medicine I (Endocrinology, Gastroenterology and Metabolic Diseases), Medical University of Innsbruck, Innsbruck, Austria.
6
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT.
7
Division of Endocrinology, Diabetes, and Metabolic Diseases, University and Hospital Trust of Verona, Verona, Italy.
8
Institute of Cardiovascular Sciences, University College London, London, U.K.
9
Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.

Abstract

MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n = 810; survey year 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type 2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-α-2-glycoprotein and positively with afamin, complement factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids. Proteomics analysis of livers from antagomiR-122-treated mice revealed novel regulators of hepatic lipid metabolism that are responsive to miR-122 inhibition. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT, n = 155), 12-month atorvastatin reduced circulating miR-122. A similar response to atorvastatin was observed in mice and cultured murine hepatocytes. Over up to 15 years of follow-up in the Bruneck Study, multivariable adjusted risk ratios per one-SD higher log miR-122 were 1.60 (95% CI 1.30-1.96; P < 0.001) for metabolic syndrome and 1.37 (1.03-1.82; P = 0.021) for type 2 diabetes. In conclusion, circulating miR-122 is strongly associated with the risk of developing metabolic syndrome and type 2 diabetes in the general population.

PMID:
27899485
PMCID:
PMC5248985
DOI:
10.2337/db16-0731
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Duality of Interest. The Medical University of Innsbruck and King’s College London filed patent applications on miRNA biomarkers.

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