{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:36:14Z","timestamp":1790876174558,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-16-1CTS-015"],"award-info":[{"award-number":["1-16-1CTS-015"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["R56AG063820"],"award-info":[{"award-number":["R56AG063820"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["P30 CA086862"],"award-info":[{"award-number":["P30 CA086862"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health","award":["1-16-1CTS-015"],"award-info":[{"award-number":["1-16-1CTS-015"]}]},{"name":"National Institutes of Health","award":["R56AG063820"],"award-info":[{"award-number":["R56AG063820"]}]},{"name":"National Institutes of Health","award":["P30 CA086862"],"award-info":[{"award-number":["P30 CA086862"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Nitric oxide (NO) stimulates mitochondrial biogenesis in skeletal muscle. However, NO metabolism is disrupted in individuals with type 2 diabetes mellitus (T2DM) potentially contributing to their decreased cardiorespiratory fitness (i.e., VO2max) and skeletal muscle oxidative capacity. We used a randomized, double-blind, placebo-controlled, 8-week trial with beetroot juice containing nitrate (NO3\u2212) and nitrite (NO2\u2212) (250 mg and 20 mg\/day) to test potential benefits on VO2max and skeletal muscle oxidative capacity in T2DM. T2DM (N = 36, Age = 59 \u00b1 9 years; BMI = 31.9 \u00b1 5.0 kg\/m2) and age- and BMI-matched non-diabetic controls (N = 15, Age = 60 \u00b1 9 years; BMI = 29.5 \u00b1 4.6 kg\/m2) were studied. Mitochondrial respiratory capacity was assessed in muscle biopsies from a subgroup of T2DM and controls (N = 19 and N = 10, respectively). At baseline, T2DM had higher plasma NO3\u2212 (100%; p &lt; 0.001) and lower plasma NO2\u2212 levels (\u221246.8%; p &lt; 0.0001) than controls. VO2max was lower in T2DM (\u221226.4%; p &lt; 0.001), as was maximal carbohydrate- and fatty acid-supported oxygen consumption in permeabilized muscle fibers (\u221226.1% and \u221225.5%, respectively; p &lt; 0.05). NO3\u2212\/NO2\u2212 supplementation increased VO2max (5.3%; p &lt; 0.01). Further, circulating NO2\u2212, but not NO3\u2212, positively correlated with VO2max after supplementation (R2= 0.40; p &lt; 0.05). Within the NO3\u2212\/NO2\u2212 group, 42% of subjects presented improvements in both carbohydrate- and fatty acid-supported oxygen consumption in skeletal muscle (vs. 0% in placebo; p &lt; 0.05). VO2max improvements in these individuals tended to be larger than in the rest of the NO3\u2212\/NO2\u2212 group (1.21 \u00b1 0.51 mL\/(kg*min) vs. 0.31 \u00b1 0.10 mL\/(kg*min); p = 0.09). NO3\u2212\/NO2\u2212 supplementation increases VO2max in T2DM individuals and improvements in skeletal muscle oxidative capacity appear to occur in those with more pronounced increases in VO2max.<\/jats:p>","DOI":"10.3390\/nu14214479","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T02:47:26Z","timestamp":1666752446000},"page":"4479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effects of Combined Inorganic Nitrate and Nitrite Supplementation on Cardiorespiratory Fitness and Skeletal Muscle Oxidative Capacity in Type 2 Diabetes: A Pilot Randomized Controlled Trial"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4418-5281","authenticated-orcid":false,"given":"Kristen D.","family":"Turner","sequence":"first","affiliation":[{"name":"Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Kronemberger","sequence":"additional","affiliation":[{"name":"Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dam","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Bock","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4559-4581","authenticated-orcid":false,"given":"Kenichi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Feider","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6205-3146","authenticated-orcid":false,"given":"Satoshi","family":"Hanada","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-2595","authenticated-orcid":false,"given":"Luis G. O.","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8078-3847","authenticated-orcid":false,"given":"Matthew P.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-8875","authenticated-orcid":false,"given":"Ethan J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fran\u00e7ois M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue C.","family":"Bodine","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Bridget","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P.","family":"Casey","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fran\u00e7ois M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3162-3804","authenticated-orcid":false,"given":"Vitor A.","family":"Lira","sequence":"additional","affiliation":[{"name":"Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Fran\u00e7ois M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of Type 2 Diabetes\u2013Global Burden of Disease and Forecasted Trends","volume":"10","author":"Khan","year":"2020","journal-title":"J. Epidemiol. Glob. 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