{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:26:49Z","timestamp":1788316009101,"version":"build-2803163510"},"reference-count":60,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T00:00:00Z","timestamp":1675987200000},"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":[[2023,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Automated insulin delivery (AID) may benefit individuals with long-standing type 1 diabetes where frequent exposure to hypoglycemia impairs counterregulatory responses. This study assessed the effect of 18 months AID on hypoglycemia avoidance and glucose counterregulatory responses to insulin-induced hypoglycemia in long-standing type 1 diabetes complicated by impaired awareness of hypoglycemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Ten participants mean\u2009\u00b1\u2009standard deviation age 49\u2009\u00b1\u200916 and diabetes duration 34\u2009\u00b1\u200916 years were initiated on AID. Continuous glucose monitoring was paired with actigraphy to assess awake- and sleep-associated hypoglycemia exposure every 3 months. Hyperinsulinemic hypoglycemic clamp experiments were performed at baseline, 6, and 18 months postintervention. Hypoglycemia exposure was reduced by 3 months, especially during sleep, with effects sustained through 18 months (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009\u2264\u20090.001) together with reduced glucose variability (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Hypoglycemia awareness and severity scores improved (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u20090.01) with severe hypoglycemia events reduced from median (interquartile range) 3 (3\u201310) at baseline to 0 (0\u20131) events\/person\u00b7year postintervention (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u20090.005). During the hypoglycemic clamp experiments, no change was seen in the endogenous glucose production (EGP) response, however, peripheral glucose utilization during hypoglycemia was reduced following intervention [pre: 4.6\u2009\u00b1\u20090.4, 6 months: 3.8\u2009\u00b1\u20090.5, 18 months: 3.4\u2009\u00b1\u20090.3\u2009mg\/(kg\u00b7min),\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u20090.05]. There were increases over time in pancreatic polypeptide (Pre:62\u2009\u00b1\u200929, 6 months:127\u2009\u00b1\u200944, 18 months:176\u2009\u00b1\u200958\u2009pmol\/L,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u20090.01), epinephrine (Pre: 199\u2009\u00b1\u200953, 6 months: 332\u2009\u00b1\u200991, 18 months: 386\u2009\u00b1\u200995\u2009pg\/mL,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u20090.001), and autonomic symptom (Pre: 6\u2009\u00b1\u20092, 6 months: 6\u2009\u00b1\u20092, 18 months: 10\u2009\u00b1\u20092,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u20090.05) responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>AID led to a sustained reduction of hypoglycemia exposure. EGP in response to insulin-induced hypoglycemia remained defective, however, partial recovery of glucose counterregulation was evidenced by a reduction in peripheral glucose utilization likely mediated by increased epinephrine secretion and, together with improved autonomic symptoms, may contribute to the observed clinical reduction in hypoglycemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/dia.2022.0506","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T11:16:03Z","timestamp":1676027763000},"page":"302-314","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":37,"title":["Automated Insulin Delivery for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes with Hypoglycemia Unawareness"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4315-5136","authenticated-orcid":false,"given":"Anneliese J.","family":"Flatt","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."},{"name":"Institute for Diabetes, Obesity &amp; Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J.","family":"Peleckis","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."},{"name":"Institute for Diabetes, Obesity &amp; Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Dalton-Bakes","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."},{"name":"Institute for Diabetes, Obesity &amp; Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huong-Lan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."},{"name":"Institute for Diabetes, Obesity &amp; Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ilany","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."},{"name":"Institute for Diabetes, Obesity &amp; Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Matus","sequence":"additional","affiliation":[{"name":"Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Malone","sequence":"additional","affiliation":[{"name":"Rory Meyers College of Nursing, New York University, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namni","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, 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