title: Islet Transplantation Provides Superior Glycemic Control With Less Hypoglycemia Compared With Continuous Subcutaneous Insulin Infusion or Multiple Daily Insulin Injections.
abstract: The aim was to compare efficacy of multiple daily injections (MDI), continuous subcutaneous insulin infusion (CSII) and islet transplantation to reduce hypoglycemia and glycemic variability in type 1 diabetes subjects with severe hypoglycemia.
  
  
  
  This was a within-subject, paired comparison of MDI and CSII and CSII with 12 months postislet transplantation in 10 type 1 diabetes subjects referred with severe hypoglycemia, suitable for islet transplantation. Individuals were assessed with HbA1c, Edmonton Hypoglycemia Score (HYPOscore), continuous glucose monitoring (CGM) and in 8 subjects measurements of glucose variability using standard deviation of glucose (SD glucose) from CGM and continuous overlapping net glycemic action using a 4 hour interval (CONGA4).
  
  
  
  After changing from MDI to CSII before transplantation, 10 subjects reduced median HYPOscore from 2028 to 1085 (P < 0.05) and hypoglycemia events from 24 to 8 per patient-year (P < 0.05). While HbA1c, mean glucose and median percent time hypoglycemic on CGM were unchanged with CSII, SD glucose and CONGA4 reduced significantly (P < 0.05). At 12 months posttransplant 9 of 10 were C-peptide positive, (5 insulin independent). Twelve months postislet transplantation, there were significant reductions in all baseline parameters versus CSII, respectively, HbA1c (6.4% cf 8.2%), median HYPOscore (0 cf 1085), mean glucose (7.1 cf 8.6 mmol L), SD glucose (1.7 cf 3.2 mmol/L), and CONGA4 (1.6 cf 3.0).
  
  
  
  In subjects with severe hypoglycemia suitable for islet transplantation, CSII decreased hypoglycemia frequency and glycemic variability compared with MDI whereas islet transplantation resolved hypoglycemia and further improved glycemic variability regardless of insulin independence.
authors.affiliation: 1 Department of Endocrinology, University of Sydney at Westmead Hospital, NSW, Australia. 2 Centre for Diabetes, Obesity and Endocrinology Research, The Westmead Institute, University of Sydney at Westmead Hospital, Sydney, Australia. 3 Department of Diabetes and Endocrinology, Westmead Hospital Westmead, NSW, Australia. 4 National Pancreas Transplant Unit, University of Sydney at Westmead Hospital, Westmead Hospital, Westmead, NSW, Australia. 5 Centre for Renal and Transplant Research, Westmead Millennium Institute, University of Sydney at Westmead, NSW, Australia. 6 Department of Renal Medicine, Westmead Hospital, NSW, Australia. 7 Department of Paediatrics, Murdoch Children's Research Institute and University of Melbourne, Victoria, Australia. 8 St Vincent's Institute, University of Melbourne, Victoria, Australia. 9 Departments of Endocrinology and Clinical Biochemistry, St Vincent's Hospital, Melbourne, Victoria, Australia. 10 Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Deborah Jane
authors.initials: DJ
authors.lastname: Holmes-Walker
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gunton
authors.forename: Wayne
authors.initials: W
authors.lastname: Hawthorne
authors.forename: Marlene
authors.initials: M
authors.lastname: Payk
authors.forename: Patricia
authors.initials: P
authors.lastname: Anderson
authors.forename: Susan
authors.initials: S
authors.lastname: Donath
authors.forename: Tom
authors.initials: T
authors.lastname: Loudovaris
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Ward
authors.forename: Thomas Wh
authors.initials: TW
authors.lastname: Kay
authors.forename: Philip J
authors.initials: PJ
authors.lastname: OʼConnell
mesh_terms: D000328:Adult; D001315:Australia; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D055104:Infusions, Subcutaneous; D007267:Injections; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D007332:Insulin Infusion Systems; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human