{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:23:17Z","timestamp":1792657397712,"version":"4.5.0"},"reference-count":38,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":2845,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH\/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score \u22654) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Eighteen subjects with T1D and IAH (mean \u00b1 SD age 50 \u00b1 9 years, T1D duration 35 \u00b1 10 years, HbA1c 8.1 \u00b1 1.0% [65 \u00b1 10.9 mmol\/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 \u00d7 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol\/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean \u00b1 SE from 2.6 \u00b1 0.1 to 3.1 \u00b1 0.2 mmol\/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420\u2013780] vs. 710 [460\u20131,260], P = 0.02; metanephrine, 2,412 [\u22123,026 to 7,279] vs. 5,180 [\u2212771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc13-1004","type":"journal-article","created":{"date-parts":[[2013,10,16]],"date-time":"2013-10-16T04:45:59Z","timestamp":1381898759000},"page":"4063-4070","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":49,"title":["Restoration of Self-Awareness of Hypoglycemia in Adults With Long-Standing Type 1 Diabetes"],"prefix":"10.2337","volume":"36","author":[{"given":"Lalantha","family":"Leelarathna","sequence":"first","affiliation":[{"name":"Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart A.","family":"Little","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine, Newcastle University, Newcastle, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Walkinshaw","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences, Sheffield University, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horng Kai","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Derriford Hospital, Plymouth, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Lubina-Solomon","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences, Sheffield University, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Kumareswaran","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette P.","family":"Lane","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine, Newcastle University, Newcastle, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Chadwick","sequence":"additional","affiliation":[{"name":"Newcastle Clinical Trials Unit, Institute of Health and Society, Newcastle University, Newcastle, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally M.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine, Newcastle University, Newcastle, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Speight","sequence":"additional","affiliation":[{"name":"AHP Research, Hornchurch, U.K."},{"name":"Australian Centre for Behavioural Research in Diabetes, Diabetes Australia\u2013Victoria, Melbourne, Victoria, Australia"},{"name":"Centre for Mental Health and Wellbeing Research, School of Psychology, Deakin University, Burwood, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Derriford Hospital, Plymouth, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon R.","family":"Heller","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences, Sheffield University, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine, Newcastle University, Newcastle, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Evans","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,11,13]]},"reference":[{"key":"2022031222203677600_B1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2337\/db10-1359","article-title":"Elimination of hypoglycemia from the lives of people affected by diabetes","volume":"60","author":"Cryer","year":"2011","journal-title":"Diabetes"},{"key":"2022031222203677600_B2","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.2337\/db10-0103","article-title":"Hypoglycemia in type 1 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