Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study. 2017

Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Diabetes & Endocrinology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK; Department of Diabetes, Endocrinology, Clinical Nutrition & Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA1c below 7·5% (58 mmol/mol). In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed. Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% [SD 8·1] when participants used usual pump therapy vs 76·2% [6·4] when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53-74, p<0·0001) and below 2·8 mmol/L by 76% (59-86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred. Use of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted. Swiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z).

UI MeSH Term Description Entries
D007003 Hypoglycemia A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH. Fasting Hypoglycemia,Postabsorptive Hypoglycemia,Postprandial Hypoglycemia,Reactive Hypoglycemia,Hypoglycemia, Fasting,Hypoglycemia, Postabsorptive,Hypoglycemia, Postprandial,Hypoglycemia, Reactive
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007332 Insulin Infusion Systems Portable or implantable devices for infusion of insulin. Includes open-loop systems which may be patient-operated or controlled by a pre-set program and are designed for constant delivery of small quantities of insulin, increased during food ingestion, and closed-loop systems which deliver quantities of insulin automatically based on an electronic glucose sensor. Pancreas, Artificial Endocrine,Programmable Implantable Insulin Pump,beta Cell, Artificial,Implantable Programmable Insulin Pump,Insulin Pump, Programmable Implantable,Pump, Programmable Implantable Insulin,Artificial Endocrine Pancreas,Artificial beta Cell,Artificial beta Cells,Cell, Artificial beta,Cells, Artificial beta,Endocrine Pancreas, Artificial,Infusion System, Insulin,Infusion Systems, Insulin,Insulin Infusion System,System, Insulin Infusion,Systems, Insulin Infusion,beta Cells, Artificial
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

Related Publications

Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
March 2016, The lancet. Diabetes & endocrinology,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
July 2014, Diabetes care,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
March 2022, The lancet. Healthy longevity,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
May 2019, The Lancet. Digital health,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
September 2014, BMJ open,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
April 2011, BMJ (Clinical research ed.),
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
January 2015, The lancet. Diabetes & endocrinology,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
February 2022, Diabetes care,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
November 2016, Diabetes care,
Lia Bally, and Hood Thabit, and Harald Kojzar, and Julia K Mader, and Jehona Qerimi-Hyseni, and Sara Hartnell, and Martin Tauschmann, and Janet M Allen, and Malgorzata E Wilinska, and Thomas R Pieber, and Mark L Evans, and Roman Hovorka
July 2016, Diabetes care,
Copied contents to your clipboard!