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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.

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King's British Heart Foundation Centre, King's College London, London, U.K.
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
King's British Heart Foundation Centre, King's College London, London, U.K.
Department of Internal Medicine I (Endocrinology, Gastroenterology and Metabolic Diseases), Medical University of Innsbruck, Innsbruck, Austria.
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT.
Division of Endocrinology, Diabetes, and Metabolic Diseases, University and Hospital Trust of Verona, Verona, Italy.
Institute of Cardiovascular Sciences, University College London, London, U.K.
Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.


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.

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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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