{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T10:55:06Z","timestamp":1676890506974},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Klin Padiatr"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\/Aim There have been no studies to date examining the\n                    effect of metformin treatment on vitamin B12 status in children and adolescents.\n                    In this prospective study, the effects of metformin on blood vitamin B12, serum\n                    methylmalonic acid (MMA), homocysteine and holo-transcobalamin-II (holo-TC-II)\n                    levels were assessed in pediatric age group.<\/jats:p><jats:p>\n          Materials and Methods This prospective study was conducted at the\n                    Pediatric Endocrinology and Adolescent Department between January 2017 and March\n                    2019. Metabolic syndrome and polycystic ovary syndrome diagnosed patients with\n                    insulin resistance and\/or impaired glucose tolerance, patients with type\n                    2 diabetes mellitus (DM) treated with metformin were enrolled in study. Blood\n                    vitamin B12, MMA, homocysteine, holo-TC-II levels and hemogram values were\n                    evaluated.<\/jats:p><jats:p>\n          Results Twenty-four patients were enrolled in study. Among these, 15\n                    (62.5%) were female. The mean age of patients was 13.7\u00b12.3\n                    (10\u201319) years. Sixteen patients were diagnosed with metabolic syndrome\n                    and 8 patients were type 2 DM. At 6-month follow-up of all patients, there was\n                    no statistically significant difference in terms of vitamin B12, homocysteine,\n                    MMA and holo-TC-II levels. A 0.6% decline in vitamin B12 levels were\n                    revealed. At 12-month follow-up of 11 patients (45.8%) (6 Type 2 DM, 5\n                    metabolic syndrome), no statistically significant difference was determined in\n                    vitamin B12, homocysteine, MMA and holo-TC-II levels. There were 6%\n                    decline in vitamin B12 levels and 10.9% increase in homocysteine levels,\n                    5.4% decrease was detected in holo-TC-II level.<\/jats:p><jats:p>\n          Conclusion Although no significant changes in the serum vitamin B12,\n                    homocysteine, MMA or holo-TC-II levels with metformin therapy were detected,\n                    long-term prospective studies with high-dose metformin treatment in pediatric\n                    population are needed to confirm our results.<\/jats:p>","DOI":"10.1055\/a-1702-2614","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T23:51:45Z","timestamp":1643932305000},"page":"221-227","source":"Crossref","is-referenced-by-count":2,"title":["Does Metformin Treatment in Pediatric Population Cause Vitamin B12\n                    Deficiency?"],"prefix":"10.1055","volume":"234","author":[{"given":"\u00d6zen","family":"Ta\u015f","sequence":"additional","affiliation":[{"name":"Ankara University Faculty of Medicine, Ankara University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tugba","family":"Kontbay","sequence":"additional","affiliation":[{"name":"Ankara University Faculty of Medicine, Pediatric Endocrinology, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozlem","family":"Dogan","sequence":"additional","affiliation":[{"name":"Ankara University Faculty of Medicine, Biochemistry, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Engin","family":"Kose","sequence":"additional","affiliation":[{"name":"Ankara University Faculty of Medicine, Pediatric\n                    Metabolism, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merih","family":"Berberoglu","sequence":"additional","affiliation":[{"name":"Ankara University Faculty of Medicine, Pediatric Endocrinology, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeynep","family":"Siklar","sequence":"additional","affiliation":[{"name":"Ankara University Faculty of Medicine, Pediatric Endocrinology, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leyla","family":"Tumer","sequence":"additional","affiliation":[{"name":"Gazi University Faculty of Medicine, Department of\n                    Pediatric Metabolic Diseases, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma Tuba","family":"Eminoglu","sequence":"additional","affiliation":[{"name":"Ankara University Faculty of Medicine, Pediatric\n                    Metabolism, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.2337\/dc20-S002","article-title":"Classification and Diagnosis of Diabetes: Standards of Medical Care in\n                    Diabetes-2020","volume":"43","author":"American Diabetes Association","year":"2020","journal-title":"Diabetes Care"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"S90","DOI":"10.2337\/dc19-S009","article-title":"9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in\n                    Diabetes-2019","volume":"42","author":"American Diabetes Association","year":"2019","journal-title":"Diabetes Care"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1515\/cclm-2014-0784","article-title":"A review of the cut-off points for the diagnosis of vitamin B12 deficiency in\n                    the general population","volume":"53","author":"R Aparicio-Ugarriza","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1210\/jc.2015-3754","article-title":"Diabetes Prevention Program Research Group. Long-term metformin use and vitamin\n                    B12 deficiency in the Diabetes Prevention Program Outcomes Study","volume":"101","author":"V R Aroda","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"ref5","first-page":"405","article-title":"Disturbance of intestinal absorption following metformin therapy","volume":"5","author":"P Berchtold","year":"1969","journal-title":"Diabetologia"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00592-014-0597-8","article-title":"Influence of duration and dose of metformin on cobalamin deficiency in type 2\n                    diabetes patients using metformin","volume":"52","author":"J Beulens","year":"2015","journal-title":"Acta Diabetologica"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e34742","DOI":"10.1371\/journal.pone.0034742","article-title":"Differences in weight status and energy-balance related behaviors among\n                    schoolchildren across Europe: the ENERGY-project","volume":"7","author":"J Brug","year":"2012","journal-title":"PLoS One"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"S238","DOI":"10.1177\/15648265080292S129","article-title":"Conclusions of a WHO Technical Consultation on folate and vitamin B12\n                    deficiencies","volume":"29","author":"B de Benoist","year":"2008","journal-title":"Food Nutr Bull"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/1474651412454924","article-title":"An observational study of the effect of metformin on B12 status and peripheral\n                    neuropathy","volume":"12","author":"S Chen","year":"2012","journal-title":"The British Journal of Diabetes & Vascular\n                    Disease"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"e192430","DOI":"10.1001\/jamapediatrics.2019.2430","article-title":"Prevalence and Trends of Overweight and Obesity in European Children From 1999\n                    to 2016: A Systematic Review and Meta-analysis","volume":"173","author":"M Garrido-Miguel","year":"2019","journal-title":"JAMA Pediatr"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ejogrb.2014.04.036","article-title":"Vitamin B12 deficiency in an adolescent girl with polycystic ovarian\n                    syndrome","volume":"179","author":"E Gourgari","year":"2014","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.3390\/nu5072475","article-title":"Metformin lowers serum cobalamin without changing other markers of cobalamin\n                    status: a study on women with polycystic ovary syndrome","volume":"5","author":"E Greibe","year":"2013","journal-title":"Nutrients"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1001\/jama.2017.6803","article-title":"Screening for Obesity in Children and Adolescents: US Preventive Services Task\n                    Force Recommendation Statement","volume":"317","author":"D C Grossman","year":"2017","journal-title":"JAMA"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1046\/j.1365-2796.1997.00231.x","article-title":"Does metformin increase the serum total homocysteine level in\n                    non-insulin-dependent diabetes mellitus?","volume":"242","author":"E K Hoogeveen","year":"1997","journal-title":"J Intern Med"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"g5226","DOI":"10.1136\/bmj.g5226","article-title":"Vitamin B12 deficiency","volume":"349","author":"A Hunt","year":"2014","journal-title":"BMJ"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"67","DOI":"10.11604\/pamj.2013.16.67.2800","article-title":"Prevalence of vitamin B12 deficiency in patients of type 2 diabetes mellitus on\n                    metformin: a case control study from Pakistan","volume":"16","author":"R Iftikhar","year":"2013","journal-title":"Pan Afr Med J"},{"key":"ref17","first-page":"179","article-title":"Association between metformin dose and vitamin B12 deficiency in patients in\n                    type 2 diabetes","volume":"98","author":"K Jiwoon","year":"2019","journal-title":"Medicine"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"dgaa150","DOI":"10.1210\/clinem\/dgaa150","article-title":"GDS Group. Vitamin B12 and Folate Concentrations in Recent-onset Type 2 Diabetes\n                    and the Effect of Metformin Treatment","volume":"105","author":"G Kanti","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1399-5448.2007.00339.x","article-title":"Peripheral neuropathy is an early complication of type 2 diabetes in\n                    adolescence","volume":"9","author":"Z Karabouta","year":"2008","journal-title":"Pediatr Diabetes"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1373\/clinchem.2007.101253","article-title":"Quantification of Methylmalonic Acid in Human Plasma with Hydrophilic\n                    Interaction Liquid Chromatography Separation and MS Detection","volume":"54","author":"H Lakso","year":"2008","journal-title":"Clinical Chemistry"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/ajh.2830340205","article-title":"Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum\n                    cobalamin, methylmalonic acid, and total homocysteine concentrations","volume":"34","author":"J Lindenbaum","year":"1990","journal-title":"Am J Hematol"},{"key":"ref22","first-page":"780","article-title":"Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: a\n                    cross-sectional study in patients with type 2 diabetes mellitus","volume":"87","author":"M Pongchaidecha","year":"2004","journal-title":"J Med Assoc Thai"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1373\/clinchem.2003.021634","article-title":"Facts and recommendations about total homocysteine determinations: an expert\n                    opinion","volume":"50","author":"H Refsum","year":"2004","journal-title":"Clin Chem"},{"key":"ref24","first-page":"327","article-title":"Jr. Association of biochemical B (12) deficiency with metformin therapy and\n                    vitamin B (12) supplements: the National Health and Nutrition Examination\n                    Survey, 1999-2006","volume":"35","author":"L Reinstatler","year":"2012","journal-title":"Diabetes Care"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1507\/endocrj.EJ13-0332","article-title":"Relationship between metformin use, vitamin B12 deficiency, hyperhomocysteinemia\n                    and vascular complications in patients with type 2 diabetes","volume":"60","author":"Y Sato","year":"2013","journal-title":"Endocr J"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.2337\/dc17-S003","article-title":"Standards of Medical Care in Diabetes-2017: Summary of Revisions","volume":"40","year":"2017","journal-title":"Diabetes Care"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1172\/JCI118763","article-title":"The effect of a subnormal vitamin B-6 status on homocysteine metabolism","volume":"98","author":"J B Ubbink","year":"1996","journal-title":"J Clin Invest"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1373\/clinchem.2010.158154","article-title":"Diagnostic Accuracy of Holotranscobalamin, Methylmalonic Acid, Serum Cobalamin,\n                    and Other Indicators of Tissue Vitamin B12 Status in the Elderly","volume":"57","author":"E Valente","year":"2011","journal-title":"Clinical Chemistry"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1046\/j.1523-1755.2001.59780234.x","article-title":"Homocysteine metabolism in renal failure","volume":"78","author":"C Van Guldener","year":"2001","journal-title":"Kidney Int Suppl"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e0147843","DOI":"10.1371\/journal.pone.0147843","article-title":"Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in\n                    Cancer","volume":"11","author":"P Vashi","year":"2016","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.2047-6310.2012.00090.x","article-title":"WHO European Childhood Obesity Surveillance Initiative 2008: weight, height and\n                    body mass index in 6-9-year-old children","volume":"8","author":"T M Wijnhoven","year":"2013","journal-title":"Pediatr Obes"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2337\/dc09-0606","article-title":"Association of metformin, elevated homocysteine and methylmalonic acid levels\n                    and clinically worsened diabetic peripheral neuropathy","volume":"33","author":"D J Wile","year":"2010","journal-title":"Diabetes Care"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1046\/j.1365-2796.2003.01213.x","article-title":"Effects of short-term treatment with metformin on serum concentrations of\n                    homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized,\n                    placebo-controlled trial","volume":"254","author":"M G Wulffele","year":"2003","journal-title":"J Intern Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1399-5448.2007.00271.x","article-title":"IDF Consensus Group. The metabolic syndrome in children and adolescents - an IDF\n                    consensus report","volume":"8","author":"P Zimmet","year":"2007","journal-title":"Pediatr Diabetes"}],"container-title":["Klinische P\u00e4diatrie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1702-2614.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T23:21:35Z","timestamp":1657668095000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1702-2614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":34,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2022,7,12]]},"published-print":{"date-parts":[[2022,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1702-2614","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0300-8630","1439-3824"],"issn-type":[{"value":"0300-8630","type":"print"},{"value":"1439-3824","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]}}}