{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:03:38Z","timestamp":1791187418267,"version":"4.1.0"},"reference-count":103,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"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":[[2014,8]]},"abstract":"<jats:p>Intensive insulin therapy (IIT) has been shown to reduce micro- and macrovascular complications in patients with type 1 diabetes mellitus (T1DM). However, IIT is associated with a significant increase in severe hypoglycemic events, resulting in increased morbidity and mortality. Optimization of glycemic control without hypoglycemia (especially nocturnal) should be the next major goal for subjects on insulin treatment. The use of insulin pumps along with continuous glucose monitors (CGMs) has made it easier but requires significant resources and patient education. Research is ongoing to close the loop by integrating the pump and the CGM using different algorithms. The currently available closed-loop system is the threshold suspend. Steps needed to achieve a near-perfect closed-loop are (1) a control-to-range system that will reduce the incidence and\/or severity of hyper- and\/or hypoglycemia by adjusting the insulin dose and (2) a control-to-target system, a fully automated or hybrid system that sets target glucose levels to individual needs and maintains glucose levels throughout the day using insulin (unihormonal) alone or with other hormones such as glucagon or possibly pramlintide (bihormonal). Future research is also focusing on better insulin delivery devices (pumps), more accurate CGMs, better predictive algorithms, and ultra-rapid-acting insulin analogs to make the closed-loop system as physiological as possible.<\/jats:p>","DOI":"10.1089\/dia.2014.0193","type":"journal-article","created":{"date-parts":[[2014,7,29]],"date-time":"2014-07-29T11:46:22Z","timestamp":1406634382000},"page":"477-490","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":61,"title":["Closed-Loop System in the Management of Diabetes: Past, Present, and Future"],"prefix":"10.1177","volume":"16","author":[{"given":"Viral N.","family":"Shah","sequence":"first","affiliation":[{"name":"University of Colorado Denver"},{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Shoskes","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beshoy","family":"Tawfik","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish K.","family":"Garg","sequence":"additional","affiliation":[{"name":"University of Colorado Denver"},{"name":"University of Colorado Denver"},{"name":"Diabetes Technology & Therapeutics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,8,1]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2013.0281"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199309303291401"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0806470"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)80085-Z"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4127"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2081"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2014.136"},{"issue":"1","key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"S-51","DOI":"10.1089\/dia.2012.0031","article-title":"Hypoglycemia, diabetes, and cardiovascular disease","volume":"14","author":"Snell-Bergeon JK","year":"2012","unstructured":"Snell-Bergeon JK, , Wadwa RP: Hypoglycemia, diabetes, and cardiovascular disease. Diabetes Technol Ther, 2012; 14(Suppl 1):S-51\u2013S-58.","journal-title":"Diabetes Technol Ther"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.06.010"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0749"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0610"},{"issue":"1","key":"e_1_3_2_14_2","first-page":"S-1","article-title":"How basal insulin analogs have changed diabetes care","volume":"13","author":"Garg SK","year":"2011","unstructured":"Garg SK, , Moser EG: How basal insulin analogs have changed diabetes care. Diabetes Technol Ther., 2011; 13(Suppl 1):S-1\u2013S-4.","journal-title":"Diabetes Technol Ther."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-1959"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2013.0228"},{"key":"e_1_3_2_17_2","first-page":"171","article-title":"A servomechanism for blood sugar control","volume":"1","author":"Kadish AH","year":"1963","unstructured":"Kadish AH: A servomechanism for blood sugar control. Biomed Sci Instrum, 1963; 1:171\u2013176.","journal-title":"Biomed Sci Instrum"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/014572178401000203"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.25.2.50"},{"issue":"1","key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"S-3","DOI":"10.1089\/dia.2013.1501","article-title":"Self-monitoring of blood glucose\u2014an overview","volume":"15","author":"Garg SK","year":"2013","unstructured":"Garg SK, , Hirsch IB: Self-monitoring of blood glucose\u2014an overview. Diabetes Technol Ther, 2013; 15(Suppl 1):S-3\u2013S-12.","journal-title":"Diabetes Technol Ther"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2009.0077"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805017"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-157-5-201209040-00508"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d3805"},{"issue":"1","key":"e_1_3_2_25_2","first-page":"S-5","article-title":"Continuous subcutaneous insulin infusion\u2014an historical perspective","volume":"12","author":"Skyler JS","year":"2010","unstructured":"Skyler JS: Continuous subcutaneous insulin infusion\u2014an historical perspective. Diabetes Technol Ther, 2010; 12(Suppl 1):S-5\u2013S-9.","journal-title":"Diabetes Technol Ther"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.11.2590"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.614"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.2003.16.7.1047"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.112.3.559"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2005.01738.x"},{"key":"e_1_3_2_31_2","first-page":"17","article-title":"Role of continuous glucose monitoring in patients with diabetes using multiple daily insulin injections","volume":"8","author":"Garg S","year":"2009","unstructured":"Garg S: Role of continuous glucose monitoring in patients with diabetes using multiple daily insulin injections. Infusyst Int, 2009; 8:17\u201321.","journal-title":"Infusyst Int"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-012-9765-1"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-1989"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.17925\/USE.2013.09.01.16"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1561"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2012.01.027"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1088\/0967-3334\/25\/4\/010"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1109\/10.740877"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681300700624"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1109\/TBME.2008.915665"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1830"},{"key":"e_1_3_2_42_2","unstructured":"Food and Drug Administration: The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems. November 9 2012. www.fda.gov\/downloads\/medicaldevices\/deviceregulationandguidance\/guidancedocuments\/ucm259305.pdf (accessed January24 2014)."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2013.0219"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00283748"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.5.817"},{"key":"e_1_3_2_46_2","first-page":"2673","article-title":"Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients","volume":"84","author":"Guerci B","year":"1999","unstructured":"Guerci B, , Meyer L, , Sall\u00e9 A, , Charri\u00e9 A, , Dousset B, , Ziegler O, , Drouin P: Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients. J Clin Endocrinol Metab, 1999; 84:2673\u20132678.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-2411"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2011.0084"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0761"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-1608"},{"key":"e_1_3_2_51_2","first-page":"159","article-title":"The \u201cGlucositter\u201d overnight automated closed loop system for type 1 diabetes: a randomized crossover trial","volume":"14","author":"Nimri R","year":"2013","unstructured":"Nimri R, , Danne T, , Kordonouri O, , Atlas E, , Bratina N, , Biester T, , Avbelj M, , Miller S, , Muller I, , Phillip M, , Battelino T: The \u201cGlucositter\u201d overnight automated closed loop system for type 1 diabetes: a randomized crossover trial. Pediatr Diabetes, 2013; 14:159\u2013167.","journal-title":"Pediatr Diabetes"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2011.0292"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1303576"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.277818"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2303"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2013.0040"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2013.0327"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2010.02964.x"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206881"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0419"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-1967"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61998-X"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d1855"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681100500606"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2010.0176"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1830"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2644"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-1631"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2013.0333"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0010"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-1796"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-1030"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0948"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2254"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229680700100208"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.121265"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681000400603"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0330"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314474"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681200600429"},{"issue":"1","key":"e_1_3_2_81_2","first-page":"S-59","article-title":"The use of insulin pumps in youth with type 1 diabetes","volume":"12","author":"Maahs DM","year":"2010","unstructured":"Maahs DM, , Horton LA, , Chase HP: The use of insulin pumps in youth with type 1 diabetes. Diabetes Technol Ther, 2010; 12(Suppl 1):S-59\u2013S-65.","journal-title":"Diabetes Technol Ther"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.19.2511"},{"issue":"1","key":"e_1_3_2_83_2","first-page":"S-11","article-title":"Insulin pump use in adults with type 1 diabetes\u2014practical issues","volume":"12","author":"Shetty G","year":"2010","unstructured":"Shetty G, , Wolpert H: Insulin pump use in adults with type 1 diabetes\u2014practical issues. Diabetes Technol Ther, 2010; 12(Suppl 1):S-11\u2013S-16.","journal-title":"Diabetes Technol Ther"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2011.0083"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2009.0128"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2009.11.014"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32835edb9d"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics3040385"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681000400127"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2005.7.28"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681200600409"},{"issue":"1","key":"e_1_3_2_92_2","first-page":"S-51","article-title":"Insulin patch pumps: their development and future in closed-loop systems","volume":"12","author":"Anhalt H","year":"2010","unstructured":"Anhalt H, , Bohannon NJ: Insulin patch pumps: their development and future in closed-loop systems. Diabetes Technol Ther, 2010; 12(Suppl 1):S-51\u2013S-58.","journal-title":"Diabetes Technol Ther"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2010.05.005"},{"key":"e_1_3_2_94_2","unstructured":"Progress Report: Single-Site Device for Insulin Infusion CGM Sensing. www.diabetesmine.com\/2013\/08\/progress-report-single-site-device-for-insulin-infusion-cgm-sensing.html (accessed April10 2014)."},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681200600421"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681100500505"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681000400632"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681300700511"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01516.x"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1177\/193229681000400223"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12107"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-012-0320-5"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309107028655"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:PHAM.0000033016.36825.2c"}],"container-title":["Diabetes Technology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/dia.2014.0193","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/dia.2014.0193","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/dia.2014.0193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:15:45Z","timestamp":1777400145000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/dia.2014.0193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":103,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1089\/dia.2014.0193"],"URL":"https:\/\/doi.org\/10.1089\/dia.2014.0193","relation":{},"ISSN":["1520-9156","1557-8593"],"issn-type":[{"value":"1520-9156","type":"print"},{"value":"1557-8593","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8]]}}}