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Epigenetic markers ...
Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes
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- García-Calzón, Sonia (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,University of Navarra,Skåne University Hospital
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- Perfilyev, Alexander (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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- Martinell, Mats (author)
- Uppsala University
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- Ustinova, Monta (author)
- Latvian Biomedical Research and Study Centre
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- Kalamajski, Sebastian (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Franks, Paul W. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Bacos, Karl (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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- Elbere, Ilze (author)
- Latvian Biomedical Research and Study Centre
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- Pihlajamäki, Jussi (author)
- University of Eastern Finland,Kuopio University Hospital
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- Volkov, Petr (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetiska komplikationer,Diabetes - Epigenetics,Lund University Research Groups,Diabetic Complications,Skåne University Hospital
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- Vaag, Allan (author)
- Steno Diabetes Center Copenhagen
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Maziarz, Marlena (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Klovins, Janis (author)
- Latvian Biomedical Research and Study Centre,University of Latvia
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- Ahlqvist, Emma (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Skåne University Hospital
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- Ling, Charlotte (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2020
- 2020
- English.
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In: Science Translational Medicine. - 1946-6234. ; 12:561
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associated with a higher risk of not responding to or not tolerating metformin with odds ratios between 1.43 and 3.09 per 1-SD methylation increase. Methylation risk scores (MRSs) of the 11 identified sites differed between glycemic responders and nonresponders with areas under the curve (AUCs) of 0.80 to 0.98. MRSs of the 4 sites associated with future metformin intolerance generated AUCs of 0.85 to 0.93. Some of these blood-based methylation markers mirrored the epigenetic pattern in adipose tissue, a key tissue in diabetes pathogenesis, and genes to which these markers were annotated to had biological functions in hepatocytes that altered metformin- related phenotypes. Overall, we could discriminate between glycemic responders/nonresponders and participants tolerant/ intolerant to metformin at diagnosis by measuring blood-based epigenetic markers in drug-naïve patients with T2D. This epigenetics-based tool may be further developed to help patients with T2D receive optimal therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- ANDIS
- diabetes
- diabetics
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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García-Calzón, S ...
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Perfilyev, Alexa ...
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Martinell, Mats
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Ustinova, Monta
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Kalamajski, Seba ...
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Franks, Paul W.
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Bacos, Karl
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Elbere, Ilze
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Pihlajamäki, Jus ...
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Volkov, Petr
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Vaag, Allan
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Groop, Leif
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Maziarz, Marlena
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Klovins, Janis
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Ahlqvist, Emma
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Ling, Charlotte
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Science Translat ...
- By the university
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Lund University