{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T06:50:53Z","timestamp":1793775053219,"version":"4.6.1"},"reference-count":36,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100020948","name":"AstraZeneca M\u00f6lndal","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020948","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008723","name":"Suomen L\u00e4\u00e4ketieteen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["6876"],"award-info":[{"award-number":["6876"]}],"id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>The aim of this study was to investigate the impact of the sodium\u2013glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] \u03bcmol \u22c5 100 g\u22121 \u22c5 min\u22121; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] \u03bcmol \u22c5 100 g\u22121 \u22c5 min\u22121; P = 0.01), an effect observed in both gray and white matter regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc24-0470","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T13:00:53Z","timestamp":1719579653000},"page":"1630-1637","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":7,"title":["SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study"],"prefix":"10.2337","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-9160","authenticated-orcid":false,"given":"Aino","family":"Latva-Rasku","sequence":"first","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"},{"name":"2Department of Endocrinology, Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3050-8692","authenticated-orcid":false,"given":"Eleni","family":"Rebelos","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0965-9365","authenticated-orcid":false,"given":"Jouni","family":"Tuisku","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6420-514X","authenticated-orcid":false,"given":"Richard","family":"Aarnio","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-5899","authenticated-orcid":false,"given":"Achol","family":"Bhowmik","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmi","family":"Keskinen","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1170-5079","authenticated-orcid":false,"given":"Sanna","family":"Laurila","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"},{"name":"3Heart Center, Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-7731","authenticated-orcid":false,"given":"Minna","family":"Lahesmaa-Hatting","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5596-0485","authenticated-orcid":false,"given":"Laura","family":"Pekkarinen","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"},{"name":"2Department of Endocrinology, Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0036-1979","authenticated-orcid":false,"given":"Henrik","family":"Isackson","sequence":"additional","affiliation":[{"name":"4Clinical Physiology and Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"},{"name":"5Integrative Physiology, Medical Cell Biology, Uppsala University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3981-2973","authenticated-orcid":false,"given":"Anna K.","family":"Kirjavainen","sequence":"additional","affiliation":[{"name":"6Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3375-8961","authenticated-orcid":false,"given":"Jukka","family":"Koffert","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Heurling","sequence":"additional","affiliation":[{"name":"7Antaros Medical AB, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-9757","authenticated-orcid":false,"given":"Lauri","family":"Nummenmaa","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"},{"name":"8Department of Psychology, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-1584","authenticated-orcid":false,"given":"Ele","family":"Ferrannini","sequence":"additional","affiliation":[{"name":"9National Research Council Institute of Clinical Physiology, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9969-3921","authenticated-orcid":false,"given":"Jonas","family":"Oldgren","sequence":"additional","affiliation":[{"name":"4Clinical Physiology and Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"},{"name":"10Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4573-517X","authenticated-orcid":false,"given":"Jan","family":"Oscarsson","sequence":"additional","affiliation":[{"name":"11Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9597-338X","authenticated-orcid":false,"given":"Pirjo","family":"Nuutila","sequence":"additional","affiliation":[{"name":"1Turku PET Centre, University of Turku, Turku, Finland"},{"name":"2Department of Endocrinology, Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"2024082720360149200_B1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41574-020-0392-2","article-title":"Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus","volume":"16","author":"Scheen","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"2024082720360149200_B2","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.2337\/db15-1356","article-title":"Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes","volume":"65","author":"Ferrannini","year":"2016","journal-title":"Diabetes"},{"key":"2024082720360149200_B3","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.2337\/dc20-2887","article-title":"Effects of the SGLT2 inhibitor dapagliflozin on energy metabolism in patients with type 2 diabetes: a randomized, double-blind crossover trial","volume":"44","author":"Op den Kamp","year":"2021","journal-title":"Diabetes Care"},{"key":"2024082720360149200_B4","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.2337\/dc15-2688","article-title":"Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes","volume":"39","author":"Daniele","year":"2016","journal-title":"Diabetes Care"},{"key":"2024082720360149200_B5","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1111\/dom.14363","article-title":"Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: a randomized, placebo-controlled, exploratory study","volume":"23","author":"Oldgren","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"2024082720360149200_B6","first-page":"1888","article-title":"14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA): evaluation in mouse of a new probe of myocardial utilization of long chain fatty acids","volume":"32","author":"DeGrado","year":"1991","journal-title":"J Nucl Med"},{"key":"2024082720360149200_B7","first-page":"455","article-title":"Biodistribution of the fatty acid analogue 18F-FTHA: plasma and tissue partitioning between lipid pools during fasting and hyperinsulinemia","volume":"48","author":"Guiducci","year":"2007","journal-title":"J Nucl Med"},{"key":"2024082720360149200_B8","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.2337\/db09-0138","article-title":"Increased brain fatty acid uptake in metabolic syndrome","volume":"59","author":"Karmi","year":"2010","journal-title":"Diabetes"},{"key":"2024082720360149200_B9","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1007\/s00259-002-0979-y","article-title":"14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle","volume":"29","author":"Takala","year":"2002","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2024082720360149200_B10","doi-asserted-by":"crossref","first-page":"408","DOI":"10.2337\/db10-0997","article-title":"Normal postprandial nonesterified fatty acid uptake in muscles despite increased circulating fatty acids in type 2 diabetes","volume":"60","author":"Labb\u00e9","year":"2011","journal-title":"Diabetes"},{"key":"2024082720360149200_B11","first-page":"1723","article-title":"Quantitation of myocardial fatty acid metabolism using PET","volume":"37","author":"Bergmann","year":"1996","journal-title":"J Nucl Med"},{"key":"2024082720360149200_B12","doi-asserted-by":"crossref","first-page":"800","DOI":"10.2337\/db20-0921","article-title":"SGLT2 inhibition does not affect myocardial fatty acid oxidation or uptake, but reduces myocardial glucose uptake and blood flow in individuals with type 2 diabetes: a randomized double-blind, placebo-controlled crossover trial","volume":"70","author":"Lauritsen","year":"2021","journal-title":"Diabetes"},{"key":"2024082720360149200_B13","doi-asserted-by":"crossref","first-page":"e210558","DOI":"10.1530\/EC-21-0558","article-title":"Effects of SGLT2 inhibition on lipid transport in adipose tissue in type 2 diabetes","volume":"11","author":"Lauritsen","year":"2022","journal-title":"Endocr Connect"},{"key":"2024082720360149200_B14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/jlcr.3589","article-title":"Automated production of [18 F]FTHA according to GMP","volume":"61","author":"Savisto","year":"2018","journal-title":"J Labelled Comp Radiopharm"},{"key":"2024082720360149200_B15","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1007\/s10278-023-00812-1","article-title":"Carimas: an extensive medical imaging data processing tool for research","volume":"36","author":"Rainio","year":"2023","journal-title":"J Digit Imaging"},{"key":"2024082720360149200_B16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fninf.2020.00003","article-title":"Magia: robust automated image processing and kinetic modeling toolbox for PET neuroinformatics","volume":"14","author":"Karjalainen","year":"2020","journal-title":"Front Neuroinform"},{"key":"2024082720360149200_B17","first-page":"711","article-title":"Clarification of a fractional uptake concept","volume":"36","author":"Thie","year":"1995","journal-title":"J Nucl Med"},{"key":"2024082720360149200_B18","first-page":"1104","article-title":"Effects of hyperglycemia on FDG uptake in human brain and glioma","volume":"35","author":"Ishizu","year":"1994","journal-title":"J Nucl Med"},{"key":"2024082720360149200_B19","first-page":"1320","article-title":"Free fatty acid uptake in the myocardium and skeletal muscle using fluorine-18-fluoro-6-thia-heptadecanoic acid","volume":"39","author":"M\u00e4ki","year":"1998","journal-title":"J Nucl Med"},{"key":"2024082720360149200_B20","doi-asserted-by":"crossref","first-page":"100176","DOI":"10.1016\/j.jlr.2022.100176","article-title":"The SGLT2 inhibitor dapagliflozin promotes systemic FFA mobilization, enhances hepatic \u03b2-oxidation, and induces ketosis","volume":"63","author":"Wallenius","year":"2022","journal-title":"J Lipid Res"},{"key":"2024082720360149200_B21","doi-asserted-by":"crossref","first-page":"101620","DOI":"10.1016\/j.molmet.2022.101620","article-title":"Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism","volume":"66","author":"Op den Kamp","year":"2022","journal-title":"Mol Metab"},{"key":"2024082720360149200_B22","doi-asserted-by":"crossref","first-page":"572","DOI":"10.2337\/db09-1322","article-title":"Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity","volume":"59","author":"Meex","year":"2010","journal-title":"Diabetes"},{"key":"2024082720360149200_B23","doi-asserted-by":"crossref","first-page":"155396","DOI":"10.1016\/j.metabol.2022.155396","article-title":"Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: a randomized, double-blind crossover trial","volume":"140","author":"Veelen","year":"2023","journal-title":"Metabolism"},{"key":"2024082720360149200_B24","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1172\/JCI107991","article-title":"Intestinal metabolism of plasma free fatty acids. Intracellular compartmentation and mechanisms of control","volume":"55","author":"Gangl","year":"1975","journal-title":"J Clin Invest"},{"key":"2024082720360149200_B25","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/dom.13228","article-title":"Morbid obesity and type 2 diabetes alter intestinal fatty acid uptake and blood flow","volume":"20","author":"Koffert","year":"2018","journal-title":"Diabetes Obes Metab"},{"key":"2024082720360149200_B26","doi-asserted-by":"crossref","first-page":"931","DOI":"10.2337\/dc18-1569","article-title":"The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity: a randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients","volume":"42","author":"Latva-Rasku","year":"2019","journal-title":"Diabetes Care"},{"key":"2024082720360149200_B27","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1177\/0271678X17734998","article-title":"Short-term interval training alters brain glucose metabolism in subjects with insulin resistance","volume":"38","author":"Honkala","year":"2018","journal-title":"J Cereb Blood Flow Metab"},{"key":"2024082720360149200_B28","doi-asserted-by":"crossref","first-page":"5928","DOI":"10.1523\/JNEUROSCI.23-13-05928.2003","article-title":"Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy","volume":"23","author":"Ebert","year":"2003","journal-title":"J Neurosci"},{"key":"2024082720360149200_B29","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/jcbfm.2013.128","article-title":"Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain","volume":"33","author":"Sch\u00f6nfeld","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"key":"2024082720360149200_B30","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cmet.2017.07.010","article-title":"Loss of brain aerobic glycolysis in normal human aging","volume":"26","author":"Goyal","year":"2017","journal-title":"Cell Metab"},{"key":"2024082720360149200_B31","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3233\/JAD-215678","article-title":"Association between use of sodium-glucose co-transporter-2 (SGLT2) inhibitors and cognitive function in a longitudinal study of patients with type 2 diabetes","volume":"87","author":"Low","year":"2022","journal-title":"J Alzheimers Dis"},{"key":"2024082720360149200_B32","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2337\/dc22-1705","article-title":"Association of sodium-glucose cotransporter 2 inhibitors with time to dementia: a population-based cohort study","volume":"46","author":"Wu","year":"2023","journal-title":"Diabetes Care"},{"key":"2024082720360149200_B33","doi-asserted-by":"crossref","first-page":"595962","DOI":"10.3389\/fendo.2020.595962","article-title":"Relationship between type 2 diabetes and white matter hyperintensity: a systematic review","volume":"11","author":"Wang","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2024082720360149200_B34","doi-asserted-by":"crossref","first-page":"9925","DOI":"10.1038\/s41598-020-67022-5","article-title":"Regional brain gray matter changes in patients with type 2 diabetes mellitus","volume":"10","author":"Roy","year":"2020","journal-title":"Sci Rep"},{"key":"2024082720360149200_B35","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.pharmthera.2012.07.006","article-title":"Insulin in the brain: there and back again","volume":"136","author":"Banks","year":"2012","journal-title":"Pharmacol Ther"},{"key":"2024082720360149200_B36","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fnmol.2018.00010","article-title":"Neuronal lipid metabolism: multiple pathways driving functional outcomes in health and disease","volume":"11","author":"Tracey","year":"2018","journal-title":"Front Mol Neurosci"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/47\/9\/1630\/780362\/dc240470.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/47\/9\/1630\/780362\/dc240470.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T16:36:45Z","timestamp":1724776605000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/47\/9\/1630\/156922\/SGLT2-Inhibitor-Dapagliflozin-Increases-Skeletal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,6,28]]},"published-print":{"date-parts":[[2024,9,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc24-0470","relation":{"has-preprint":[{"id-type":"doi","id":"10.2337\/figshare.26042449","asserted-by":"object"},{"id-type":"doi","id":"10.2337\/figshare.26042449.v1","asserted-by":"object"}]},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}