Horm Metab Res 2015; 47(01): 9-15
DOI: 10.1055/s-0034-1394455
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Outcomes for Adults with Type 1 Diabetes Referred with Severe Hypoglycaemia and/or Referred for Islet Transplantation to a Specialist Hypoglycaemia Service

M. L. Byrne
1   Diabetes Research Group, King’s College London, London, UK
,
D. Hopkins
2   Department of Diabetes, King’s College Hospital, London, UK
,
W. Littlejohn
3   Institute of Liver Studies, King’s College Hospital, London, UK
,
R. Beckford
3   Institute of Liver Studies, King’s College Hospital, London, UK
,
P. Srinivasan
3   Institute of Liver Studies, King’s College Hospital, London, UK
,
N. Heaton
3   Institute of Liver Studies, King’s College Hospital, London, UK
,
S. A. Amiel
1   Diabetes Research Group, King’s College London, London, UK
,
P. Choudhary
1   Diabetes Research Group, King’s College London, London, UK
› Author Affiliations
Further Information

Publication History

received 04 July 2014

accepted 15 October 2014

Publication Date:
06 November 2014 (online)

Abstract

Islet transplantation alone (ITA) is indicated for patients with type 1 diabetes (T1D) with disabling severe hypoglycaemia (SH) despite optimised medical therapy. We examined outcomes for patients referred to an islet transplant unit with recurrent SH. Retrospective case note audit of 45 patients with ≥1 SH per year who were referred to our ITA unit between 2009–2012; 36 patients attended follow-up appointments. The cohort was 52.8% male, mean (± SD) age 43.9 (± 11.4) years, and duration of diabetes 26.5 (± 12.9) years. Baseline HbA1c was 8.3% (± 1.7) (67.2 mmol/mol), median (IQR) frequency of SH was 6.0 (2.0–24.0) per/patient/year and 83.3% had impaired awareness of hypoglycaemia (IAH). 80.6% of patients were referred from other secondary diabetes services, 22.2% had completed structured education, and 30.6% were using continuous subcutaneous insulin infusion (CSII). Seventeen patients were optimised with conventional therapy; SH reduced from 2.0 (1.5–9.0) to 0.0 (0.0–0.5) episodes/patient/year; p<0.001, and there was concurrent improvement in HbA1c (8.1–7.7%; 65.0 vs. 60.7 mmol/mol; p=0.072). Ten patients were listed for transplantation as they were not optimised despite structured education, CSII, and continuous glucose monitoring (CGM). The remaining 9 had a reduction in SH [7.0 (4.8–40.5) to 4.0 (2.5–6.3) episodes/patient/year; p=0.058] and either left the service (n=5) or are still being optimised (n=4). In conclusion, 47.2% of patients presenting with problematic hypoglycaemia resolved with optimal medical therapy, with a further 25% achieving clinically relevant improvement, however 27.8% required transplantation despite access to all therapies. Provision of expertise in hypoglycaemia management is essential to focus limited transplant resources on those who need it most.

 
  • References

  • 1 Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013; 36: 1384-1395
  • 2 McCrimmon RJ, Frier BM. Hypoglycaemia, the most feared complication of insulin therapy. Diabete Metab 1994; 20: 503-512
  • 3 Geddes J, Schopman JE, Zammitt NN, Frier BM. Prevalence of impaired awareness of hypoglycaemia in adults with Type 1 diabetes. Diabet Med 2008; 25: 501-504
  • 4 Hopkins D, Lawrence I, Mansell P, Thompson G, Amiel S, Campbell M, Heller S. Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE experience. Diabetes Care 2012; 35: 1638-1642
  • 5 Choudhary P, Parrott NR, Birtles L, Rutter MK. Islet cell transplantation: current status in the UK. Practical Diabetes 2012; 29: 280-285
  • 6 Pickup JC, Sutton AJ. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med 2008; 25: 765-774
  • 7 Garg S, Brazg RL, Bailey TS. Reduction in duration of hypoglycemia by automatic suspension of insulin delivery: the in-clinic ASPIRE study. Diabetes Technol Ther 2012; 14: 205-209
  • 8 Barton FB, Rickels MR, Alejandro R, Hering BJ, Wease S, Naziruddin B, Oberholzer J, Odorico JS, Garfinkel MR, Levy M, Patton F, Berney T, Secchi A, Messinger S, Senior PA, Maffi P, Possett A, Stock P, Kaufman DB, Luo X, Kandeel F, Cagliero E, Turgeon NA, Witkowski P, Naji A, O’Connell PJ, Greenbaum C, Kudva YC, Brayman KL, Aull MJ, Larsen C, Kay TWH, Fernnandez LA, Vantyghem M-C, Bellin M, Shapiro J. Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care 2012; 35: 1436-1445
  • 9 Brooks AM, Walker N, Aldibbiat A, Hughes S, Jones G, de havilland J, Choudhary P, Huang GC, Parrott N, Mcgowan NWA, Casey J, Mumford L, Barker P, Burling K, Hovorka R, Walker M, Smith RM, Forbes S, Rutter MK, Amiel S, Rosenthal MJ, Johson P, Shaw JAM. Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations. Am J Transplant 2013; 13: 3236-3243
  • 10 UK Hypoglycaemia Study Group . Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007; 50: 1140-1147
  • 11 DVLA. At a glance guide to the current medical standards of fitness to drive for medical professionals. 2013 2014
  • 12 CITR. Collaborative Islet Transplant Registry Seventh Annual Report. 2011 2014
  • 13 Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Clin Transplant 2005; 19: 433-455
  • 14 Bott S, Bott U, Berger M, Mühlhauser I. Intensified insulin therapy and the risk of severe hypoglycaemia. Diabetologia 1997; 40: 926-932
  • 15 Gruessner AC, Sutherland DE, Gruessner RW. Long-term outcome after pancreas transplantation. Curr Opin Organ Transplant 2012; 17: 100-105
  • 16 Choudhary P, Geddes J, Freeman JV, Emery CJ, Heller SR, Frier BM. Frequency of biochemical hypoglycaemia in adults with Type 1 diabetes with and without impaired awareness of hypoglycaemia: no identifiable differences using continuous glucose monitoring. Diabetic Med 2010; 27: 666-672
  • 17 Weinstock RS, Xing D, Maahs DM, Michels A, Rickels MR, Peters AL, Bergenstal RM, Harris B, Dubose SN, Miller KM, Beck RW. T1D Exchange Clinic Network. Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J Clin Endocrinol Metab 2013; 98: 3411-3419
  • 18 NHS Blood and Transplant. Organ Donation and Transplantation Activity Data: United Kingdom. 2014 2014
  • 19 NICE Guidelines. IPG257: Allogeneic Pancreatic Islet Cell Transplantation for Type 1 Diabetes Mellitus. 2008 2014
  • 20 Health and Social Care Information Centre. National Diabetes Audit 2011–2012 – Report 1: Care Processes and Treatment Targets. 2013
  • 21 White HD, Goenka N, Furlong NJ, Saunders S, Morrison G, Langridge P, Paul P, Ghatak A, Weston PJ. The U.K. service level audit of insulin pump therapy in adults. Diabet Med 2014; 31: 412-418
  • 22 Ly TT, Nicholas JA, Retterath A, Lim EM, Davis EA, Jones TW. Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs. standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial. JAMA 2013; 310: 1240-1247
  • 23 Choudhary P, Ramasamy S, Green L, Gallen G, Pender S, Brackenridge A, Amiel SA, Pickup JC. Real-time continuous glucose monitoring significantly reduces severe hypoglycemia in hypoglycemia-unaware patients with type 1 diabetes. Diabetes Care 2013; 36: 4160-4162
  • 24 Little SA, Leelarathna L, Walkinshaw E, Tan HK, Chapple O, Lubina-Solomon A, Chadwick TJ, Barendse S, Stocken DD, Brennand C, Marshall SM, Wood R, Speight J, Kerr D, Flanagan D, Heller SRE, Evans ML, Shaw JA. Recovery of Hypoglycemia Awareness in Long-Standing Type 1 Diabetes: A Multicenter 2×2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-Monitoring (HypoCOMPaSS). Diabetes Care 2014; 37: 2114-2122
  • 25 de Zoysa N, Rogers H, Stadler M, Gianfrancesco C, Beveridge S, Britneff E, Choudhary P, Elliot J, Heller S, Amiel SA. A Psychoeducational Program to Restore Hypoglycemia Awareness: The DAFNE-HART Pilot Study. Diabetes Care 2014; 37: 863-866
  • 26 Smith CB, Choudhary P, Pernet A, Hopkins D, Amiel SA. Hypoglycemia unawareness is associated with reduced adherence to therapeutic decisions in patients with type 1 diabetes: evidence from a clinical audit. Diabetes Care 2009; 32: 1196-1198
  • 27 Dunn JT, Cranston I, Marsden PK, Amiel SA, Reed LJ. Attenuation of amygdala and frontal cortical responses to low blood glucose concentration in asymptomatic hypoglycemia in type 1 diabetes: a new player in hypoglycemia unawareness?. Diabetes 2007; 56: 2766-2773