{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:02:14Z","timestamp":1777557734196,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Technology &amp; Therapeutics"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The ability to simulate in silico experiments is crucial for fast and cost-effective preliminary studies prior to clinical trials. We present an in silico approach to the design of optimal pramlintide-to-insulin (P\/I) ratios, using our computer simulator of the human metabolic system, with a population of virtual adult type 1 diabetes mellitus patients and with individual parameters modified to account for the dynamic effects of pramlintide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>A model of pramlintide action on gastric emptying was built using data of 15 type 1 diabetes mellitus subjects studied twice with a standardized dual-tracer meal on placebo and pramlintide, which was incorporated in our type 1 diabetes simulator. Extensive in silico experiments on 100 virtual subjects were performed to optimize the co-administration of pramlintide and insulin prior to its submission to clinical trials; several P\/I ratios were tested in terms of efficacy, in attenuating postprandial hyperglycemia, and in hypoglycemia safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In silico experiments estimated the optimal P\/I ratio to be 9\u2009\u03bcg of pramlintide per unit (U) of insulin. Additional simulations narrowing the investigated range indicated that P\/I ratios of 8 and 10\u2009\u03bcg\/U would achieve similar performance. Moreover, simulation results suggested that in clinical trials, insulin boluses should be reduced by approximately 21% at a P\/I ratio of 9\u2009\u03bcg\/U to account for the effects of pramlintide and avoid postprandial hypoglycemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We can assert that a valid simulation model of pramlintide action was developed, leading to in silico estimation of optimal pramlintide:insulin co-administration ratio. Clinical trials will confirm (or adjust) this initial estimation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/dia.2013.0054","type":"journal-article","created":{"date-parts":[[2013,7,18]],"date-time":"2013-07-18T09:42:39Z","timestamp":1374140559000},"page":"802-809","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["In Silico Design of Optimal Ratio for Co-Administration of Pramlintide and Insulin in Type 1 Diabetes"],"prefix":"10.1177","volume":"15","author":[{"given":"Francesco","family":"Micheletto","sequence":"first","affiliation":[{"name":"University of Padova","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Dalla Man","sequence":"additional","affiliation":[{"name":"University of Padova","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orville","family":"Kolterman","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, LLC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine","family":"Chiquette","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, LLC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, LLC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Schirra","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians University","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Kovatchev","sequence":"additional","affiliation":[{"name":"University of Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Cobelli","sequence":"additional","affiliation":[{"name":"University of Padova","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2013,10,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1032"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2006.12.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1109\/RBME.2009.2036073"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.11.3093"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.11.3102"},{"key":"e_1_3_3_7_2","volume-title":"Die Theoretischen Grundlagen und die Praktische Verwendbarkeit der Gerichtlich-Medizinischen Alkoholbestimmung","author":"Widmark EMP","year":"1932","unstructured":"Widmark EMP. 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