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Metabolic homeostasis arises from feedback and feed-forward interactions among (at least) all four of glucose, insulin, glucagon, and cortisol. Quantifying such tetrapartite interactions in the fasting (endogenously regulated) state overnight could elucidate very early regulatory disruption. In the present study, healthy subjects without diabetes (ND; n = 20) and patients with Type 2 diabetes (T2D; n = 21) were investigated by repeated overnight blood sampling of all four of glucose, insulin, glucagon, and cortisol concentrations. To obviate confounding by hormone-specific disappearance rates, analyses were performed at the level of production (glucose) or secretion (insulin, glucagon, and cortisol) rates estimated by regularized deconvolution analysis. Then, a novel method for quantifying the loss of homeostasis among glucose, insulin, and glucagon (and, when available, cortisol) secretion patterns was developed. Potential early stage prediabetic candidates were identified. The new methodology avoids many of the difficulties encountered in the conventional estimation of insulin-glucose sensitivity or resistance, while incorporating the dynamics of the key coregulators under fasting conditions. <\/jats:p>","DOI":"10.1152\/ajpendo.00078.2018","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T14:25:38Z","timestamp":1552400738000},"page":"E998-E1011","source":"Crossref","is-referenced-by-count":4,"title":["A novel measure of glucose homeostasis (or loss thereof) comprising the joint dynamics of glucose, insulin, glucagon, and cortisol"],"prefix":"10.1152","volume":"316","author":[{"given":"Daniel M.","family":"Keenan","sequence":"first","affiliation":[{"name":"Department of Statistics, University of Virginia, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes D.","family":"Veldhuis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananda","family":"Basu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Center of Diabetes Technology, University of Virginia School of Medicine, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Basu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Center of Diabetes Technology, University of Virginia School of Medicine, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1215"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1979.236.6.E667"},{"key":"B3","first-page":"770","volume":"80","author":"Bright GM","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3240-x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1109\/18.986021"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280882"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1177\/193229681300700308"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0300619101"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00494.2011"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00477.2010"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00201.2010"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00027.2015"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9892.2012.00795.x"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.5.E908"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0116"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1991.260.5.E801"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/BF00400263"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0005"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00078.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,24]],"date-time":"2019-09-24T05:37:45Z","timestamp":1569303465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00078.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,1]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6,1]]}},"alternative-id":["10.1152\/ajpendo.00078.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00078.2018","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,1]]}}}