{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:32:01Z","timestamp":1769632321911,"version":"3.49.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Agriculture"},{"name":"The Ministry of Agriculture"},{"name":"The Ministry of Agriculture"},{"name":"The Ministry of Agriculture"},{"name":"The Ministry of Agriculture"},{"name":"The Ministry of Agriculture"},{"name":"Nature and Food Quality"},{"name":"Nature and Food Quality"},{"name":"Nature and Food Quality"},{"name":"Nature and Food Quality"},{"name":"Nature and Food Quality"},{"name":"Nature and Food Quality"},{"name":"Senter-Novem of The Netherlands"},{"name":"Senter-Novem of The Netherlands"},{"name":"Senter-Novem of The Netherlands"},{"name":"Senter-Novem of The Netherlands"},{"name":"Senter-Novem of The Netherlands"},{"name":"Senter-Novem of The Netherlands"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Lifestyle influences endocrine, metabolic and cardiovascular homeostasis. This study investigated the impact of diet and oral anti-diabetic medication on cardio-metabolic health in human-sized diabetic pigs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>After a growing pre-phase from ~30 to ~69 kg during which domestic pigs were fed either a low fat, low sucrose diet (group A) or a fast food-type diet elevated in lard (15%) and sucrose (40%) (group B), the pigs were subdivided in 5 groups (n = 7\u20138 pigs per group). Group 1, normal pigs from group A on a low fat, low sugar (<jats:bold>L<\/jats:bold>) pig diet and group 2, normal pigs from group B on a high lard (25%), sucrose-fructose (40%), cholesterol (1%) fast food-type (<jats:bold>F<\/jats:bold>) diet. Diabetes (<jats:bold>D<\/jats:bold>) was induced in group B pigs by streptozotocin and group 3 received the <jats:bold>F<\/jats:bold> diet (<jats:bold>DF<\/jats:bold>), group 4 received the <jats:bold>F<\/jats:bold> diet with <jats:bold>A<\/jats:bold>nti-diabetic medication metformin (2 g.day<jats:sup>-1<\/jats:sup>)-pioglitazone (40 mg.day<jats:sup>-1<\/jats:sup>) (<jats:bold>DFA<\/jats:bold>) and group 5 switched to a <jats:bold>P<\/jats:bold>lant-<jats:bold>F<\/jats:bold>ish oil (25%), <jats:bold>S<\/jats:bold>lowly digestible <jats:bold>s<\/jats:bold>tarch (40%) diet (<jats:bold>DPFS<\/jats:bold>). The <jats:bold>F<\/jats:bold> and <jats:bold>PFS<\/jats:bold> diets were identical for fat, carbohydrate and protein content but only differed in fat and carbohydrate composition. The 5 pig groups were followed up for 7 weeks until reaching ~120 kg.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In normal pigs, the <jats:bold>F<\/jats:bold> diet predisposed to several abnormalities related to metabolic syndrome. Diabetes amplified the inflammatory and cardiometabolic abnormalities of the <jats:bold>F<\/jats:bold> diet, but both oral <jats:bold>FA<\/jats:bold> medication and the <jats:bold>PFS<\/jats:bold> diet partially corrected these abnormalities (mean\u00b1SEM) as follows: Fasting plasma TNF-\u0251 (pg.ml<jats:sup>-1<\/jats:sup>) and NEFA (mmol.l<jats:sup>-1<\/jats:sup>) concentrations were high (p&lt;0.02) in <jats:bold>DF<\/jats:bold> (193\u00b155 and 0.79\u00b10.16), intermediate in <jats:bold>DFA<\/jats:bold> (136\u00b140 and 0.57\u00b1012) and low in <jats:bold>DPFS<\/jats:bold> pigs (107\u00b131 and 0.48\u00b10.19). Meal intolerance (response over fasting) for glucose and triglycerides (area under the curve, mmol.h<jats:sup>-1<\/jats:sup>) and for lactate (3-h postprandial, mmol.l<jats:sup>-1<\/jats:sup>) was high (p&lt;0.03) in <jats:bold>DF<\/jats:bold> (489\u00b1131, 8.6\u00b14.8 and 2.2\u00b10.6), intermediate in <jats:bold>DFA<\/jats:bold> (276\u00b1145, 1.4\u00b11.1 and 1.6\u00b10.4) and low in <jats:bold>DPFS<\/jats:bold> (184\u00b162, 0.7\u00b11.8 and 0.1\u00b10.1). Insulin-mediated glucose disposal (mg.kg<jats:sup>-1<\/jats:sup>.min<jats:sup>-1<\/jats:sup>) showed a numerical trend (p = NS): low in <jats:bold>DF<\/jats:bold> (6.9\u00b12.2), intermediate in <jats:bold>DFA<\/jats:bold> (8.2\u00b11.3) and high in <jats:bold>DPFS<\/jats:bold> pigs (10.4\u00b12.7). Liver weight (g.kg<jats:sup>-1<\/jats:sup> body weight) and liver triglyceride concentration (g.kg<jats:sup>-1<\/jats:sup> liver) were high (p&lt;0.001) in <jats:bold>DF<\/jats:bold> (23.8\u00b12.0 and 69\u00b114), intermediate in <jats:bold>DFA<\/jats:bold> (21.1\u00b12.0 and 49\u00b115) and low in <jats:bold>DPFS<\/jats:bold> pigs (16.4\u00b10.7 and 13\u00b12.0). Aorta fatty streaks were high (p&lt;0.01) in <jats:bold>DF<\/jats:bold> (16.4\u00b15.7%), intermediate in <jats:bold>DFA<\/jats:bold> (7.4\u00b14.5%) and low in <jats:bold>DPFS<\/jats:bold> pigs (0.05\u00b10.02%).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This translational study using pigs with induced type 2 diabetes provides evidence that a change in nutritional life style from fast food to a plant-fish oil, slowly digestible starch diet can be more effective than sole anti-diabetic medication.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0257299","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T03:59:48Z","timestamp":1634788788000},"page":"e0257299","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beneficial effects of a plant-fish oil, slow carbohydrate diet on cardio-metabolic health exceed the correcting effects of metformin-pioglitazone in diabetic pigs fed a fast-food diet"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8238-4770","authenticated-orcid":true,"given":"Sietse J.","family":"Koopmans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-1152","authenticated-orcid":true,"given":"Heleen M. M.","family":"van Beusekom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Josef","family":"van der Staay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gisabeth","family":"Binnendijk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Hulst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zlaw","family":"Mroz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariette T.","family":"Ackermans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lambertus","family":"Benthem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"pone.0257299.ref001","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s00125-017-4361-9","article-title":"Metformin for diabetes prevention: Insights gained from the diabetes prevention program\/diabetes prevention program outcomes study","volume":"60","author":"VR Aroda","year":"2017","journal-title":"Diabetologia"},{"key":"pone.0257299.ref002","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/MOL.0000000000000532","article-title":"Metformin, lipids and atherosclerosis prevention","volume":"29","author":"AJ Jenkins","year":"2018","journal-title":"Current opinion in lipidology"},{"key":"pone.0257299.ref003","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.4049\/jimmunol.0804341","article-title":"The peroxisome proliferator-activated receptor \u03b3 agonist pioglitazone improves cardiometabolic risk and renal inflammation in murine lupus","volume":"183","author":"W Zhao","year":"2009","journal-title":"The Journal of Immunology"},{"key":"pone.0257299.ref004","doi-asserted-by":"crossref","first-page":"730","DOI":"10.2337\/dc10-2083","article-title":"Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: changes associated with pioglitazone","volume":"34","author":"HS Sacks","year":"2011","journal-title":"Diabetes care"},{"key":"pone.0257299.ref005","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.2337\/diacare.25.12.2165","article-title":"The Diabetes Prevention Program (DPP): description of lifestyle intervention","volume":"25","author":"Diabetes Prevention Program (DPP) Research Group","year":"2002","journal-title":"Diabetes care"},{"key":"pone.0257299.ref006","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1056\/NEJMoa1212914","article-title":"Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes","volume":"369","author":"Look AHEAD Research Group","year":"2013","journal-title":"New England journal of medicine"},{"key":"pone.0257299.ref007","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"WC Knowler","year":"2002","journal-title":"The New England journal of medicine"},{"key":"pone.0257299.ref008","doi-asserted-by":"crossref","first-page":"611","DOI":"10.7326\/0003-4819-142-8-200504190-00009","article-title":"The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial","volume":"142","author":"TJ Orchard","year":"2005","journal-title":"Annals of internal medicine"},{"key":"pone.0257299.ref009","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1753-6405.2010.00503.x","article-title":"Lifestyle and medication interventions for the prevention or delay of type 2 diabetes mellitus in prediabetes: a systematic review of randomised controlled trials","volume":"34","author":"A Yuen","year":"2010","journal-title":"Australian and New Zealand journal of public health"},{"key":"pone.0257299.ref010","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/sj.ejcn.1601413","article-title":"Nutritional habits in the Mediterranean Basin. 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