20 th. Diabetic ketoacidosis: update on management and prevention. Friday. October Innsbruck Hall ISPAD 2017

Transcription

1 ISPAD 2017 October 18 th - 21 st Innsbruck - Austria A.Menarini Diagnostics Satellite Symposium Diabetic ketoacidosis: update on management and prevention 20 th Friday October Innsbruck Hall Chairperson: Joseph Wolfsdorf (USA)

2 A.Menarini Diagnostics Satellite Symposium Diabetic ketoacidosis: update on management and prevention Chairperson: Joseph Wolfsdorf (USA)

3 Index How can we prevent recurrent-dka?... Birgit Rami-Merhar (Austria) DKA update in 2017: new challenges and solutions... Thomas Danne (Germany) The next challenge: serious gaming and virtual coaching in diabetes education... Gert Jan van der Burg (The Netherlands) Curricula Vitae... 11

4 Birgit Rami-Merhar MD, Assoc. Professor, MBA University Children s Hospital Medical University of Vienna Austria How can we prevent recurrent-dka? Diabetic Ketoacidosis (DKA) is still the most frequent cause of death in young patients with T1 diabetes (Fig 1). Various efforts and campaigns to reduce Onset-DKA have shown diverging results in the aim to reduce Onset-DKA. Recurrent-DKA in patients with already diagnosed T1D remains a relevant problem in pediatric diabetology. Long-term benchmarking data e.g. in Germany and Austria have shown a reduction of recurrent-dka over the time. Comparisons between different registries have shown clear differences in the frequency of DKA, which also led to a harmonization of Hba1c-targets. Most countries now recommend the HbA1c-target of < 7,5 % (58 mmol/mol) for all age groups, while some countries already suggest an even lower HbA1c-target. Recent research has proven, that lower HbA1c targets no only reduces the risk for DKA and long-term vascular complications, but also does not lead to an increase of severe hypoglycemia. Initiatives like SWEET are leading the way to improve the standards of care for children with diabetes via establishing centers of references, setting standards for multidisciplinary teams, benchmarking and improvement of educational materials. The aim to reduce recurrent-dka and its complications clearly must focus on the well-known risk groups: older girls, patients who omit insulin, psychiatric disorders, patients with unstable family circumstances, DKA is the most common cause of death in young T1D-patients Study or country (reference) British Diabetes Association Cohort Study (Laing et al.) Sweden (Dahlquist and Kallen) EURODIAB (12 countries) (Patterson et al.) Period of study Table 1. Mortality in Youth Diagnosed with Type 1 Diabetes Cohort 23,752 youth <30 yo at dx 10,200 youth <14 yo at dx 28,887 youth <15 yo at dx Person-years of exposure 317,522 81, ,061 <60 yo 759 total deaths 170 (22%) DRD Based on death certificates <37 yo 78 deaths 23 (29%) DRD Based on death certificates <30 yo 141 deaths 41 (35%) DRD Based on death certificates and infomation from centers DRD Onset deaths excluded Male deaths=54% DKA; 18% SH Female deaths=76% DKA; 6% SH All causes=15% DKA; 3% SH 6 new-onset T1D (DKA) 1 SH (alcohol) 14 DKA (60%) (18% of all deaths) 17 dead in bed (no cause on autopsy including normal glucose levels) 2 myocardial infarction Onset deaths excluded 27 DKA (66%) (19% of all deaths) 5 SH (12%) (4% of all deaths) 7 dead in bed (no cause;±autopsy) DKA, diabetic ketoacidosis; DRD, diabetes-related death; dx, diagnosis; SH, severe hypoglycemia; T1D, type 1 diabetes; yo, years old. Realsen et al. DIABETES TECHNOLOGY & THERAPEUTICS 2012 Mortality Causes of DRD 4

5 Children with poor metabolic control or previous episodes of DKA, Children with limited access to medical services (also with health insurance issues) and migration background. The type of insulin-therapy itself does not show differences anymore, in specific CSII does not lead to a higher risk for DKA anymore. The aim of diabetes teams around the world and scientific organizations like ISPAD is to improve the standards of care (including access to medical care, blood test strips, insulin, diabetes education, CSII and CGMS) for all children and adolescents with diabetes and then consequently reduce the rates of recurrent DKA. Identify T1D-children at risk for recurrent DKA (1-10%/patient/year), ISPAD 2014 Children who omit insulin Children with poor metabolic control or previous episodes of DKA Gastroenteritis with persistent vomiting and inability to maintain hydration Children with psychiatric disorders, including those with eating disorders Children with difficult or unstable family circumstances (e.g. parental abuse) Peripubertal and adolescent girls Binge alcohol consumption Children with limited access to medical services Insulin pump therapy (as only rapid- or short-acting insulin is used in pumps, interruption of insulin delivery for any reason rapidly leads to insulin deficiency) -still verifiable?? ISPAD

6 Thomas Danne Chief Physician, Department of General Pediatrics, Diabetes, Endocrinology & Clinical Research, Diabetes center for Children and Adolescents, Children s Hospital Auf der Bult, Hannover Medical School, Germany. DKA update in 2017: new challenges and solutions Diabetic ketoacidosis (DKA) is the most common cause of mortality in children and adolescents with diabetes at onset of diabetes or in children with established diabetes. A recent analysis of 49,859 individuals <18 years with type 1 diabetes of three multinational registries/audits with similarly advanced, yet differing, health care systems identified females, ethnic minorities, and HbA1c above target being associated with an increased risk of DKA. DKA results from absolute or relative deficiency of circulating insulin and the combined effects of increased levels of the counterregulatory hormones: catecholamines, glucagon, cortisol and growth hormone. Absolute insulin deficiency occurs in previously undiagnosed diabetes mellitus and when patients on treatment deliberately or inadvertently do not take insulin injections. Even when best practices for insulin pump therapy are followed, infusion-set failure occurs in some patients, potentially leading to DKA. Evidence of unexplained hyperglycemia warrants particular vigilance in the presence of sudden glucose elevation (>250 mg/dl) that is unrelated to a meal and accompanied by nausea or vomiting. Diabetic ketoacidosis: update on management and prevention Is DKA prevention possible? 5 steps to do better: Educate Detect Interpret urinary ketones Interpret blood ketones Implement hospital guidelines Management of an episode of DKA is not complete until its cause has been identified and an attempt made to treat it. Home measurement of blood β-hydroxybutyrate when compared to urine ketone testing decreases diabetes-related hospital visits (both emergency department visits and hospitalizations) by the early identification and treatment of ketosis. Parents and patients should learn how to recognize and treat impending DKA with additional rapid- or short-acting insulin and oral fluids. 6

7 If glucose levels do not normalize within 2 hours of administering a correction bolus, the patient should check his or her blood ketones. Urine ketone determination should be abandoned since ketones show up late in urine compared with blood and also decrease later after supplemental insulin is administered. Since ketones in the blood or urine signal an advanced failure in insulin delivery, the patient should also administer rapid- or fast-acting insulin by pen or syringe, based on his or her correction dose algorithm. The current infusion set and infusion reservoir/ cartridge should be replaced during this time as well. A blood ketone level of > mmol/l (urine ketones, negative to small) may require a larger dose of insulin (e.g., twice the correction dose). If blood ketones are above 1.3 mmol/l (urine ketones, moderate to large), the patient should call the diabetes team for advice about additional insulin replacement, since this level of ketones indicates initial risk for acidosis. Blood ketones >3 mmol/l (urine ketones, large) require emergency care. A recent development concerns adjunct therapy with SGLT-2 or SGLT1&2-inhibitors. These oral drugs seem to be associated with euglycemic DKA and ketosis. Patients with type 1 or type 2 diabetes who Teach what to do Calculating 10% or 20% of daily dose to correct blood ß-ketones above 1.5 mmol/l Give 20% of the total daily dose of rapid-acting insulin for correction mmoi/l experience nausea, vomiting, or malaise, or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy, should be promptly evaluated for the presence of urine and/or serum ketones. In conclusion, prevention of DKA appears to be an elusive goal. However, early detection and proper management saves lives. β-ketone-measurement has an important role in this respect as it allows realtime DKA diagnosis and management. 7

8 Gert Jan van der Burg Pediatrician Medical Information Innovation Officer Gelderse Vallei Hospital, The Netherlands The next challenge: serious gaming and virtual coaching in diabetes education In health care we see a paradigm shift from disease management by professionals to self-manangement by patients, supported by ehealth and smart technology. Frequent self-monitoring of blood glucose has shown to be significantly associated with better metabolic control. Patients however, encounter many barriers while dealing with diabetes self-management in their everyday life. Interventions are needed that engage, motivate and influence selfmanagement behaviours. Since smartphones are PERvasive serious GAMes supported by virtual coaching common nowadays, they are a potentially powerful PERGAMON tool to assist diabetes patients in managing their disease. The use of smartphone based serious games and gamification techniques, combined with wireless sensors and virtual coaching is expected to have a positive impact on self-management skills and adherence to the diabetes regime. In the PERGAMON project (PERvasive serious Games supported by virtual coaching), a prototype platform was developed and tested. It consists of: Ground Layer (the central data hub) Sensor Network (monitoring the player by wireless sensors) Gamification Platform (accessible through a web site) Serious Game (the main 3D game and the mini games) Virtual Coach (delivering personalized assistance to the player in the real life) 8

9 Many lessons were learned from the project: first of all, the technology used, has to be integrated in the daily routine of the patients in a non-obtrusive way. Every extra action on top of the obligatory daily diabetes procedures for the user, has to be avoided, unless it is fun, challenging, or part of the game. Manually entering of glucose data in one of the components appeared to be a barrier for adherence to the system. The technology used has to be full proof and intuitive to use. Children in the age group of our project are very critical of the performance, stability and logic of a game. We observed that frustrations about these aspects easily led to discarding of the platform. In general we learned how essential it is to have a good balance between flawless and non-obtrusive technology, challenging but not to difficult gameplay, and excellent fine-tuning to the age group. The PERGAMON platform is the first example of a connection of the real world of diabetes to a virtual game world. Although it was not tested extensively in a large group of users, the present findings have shown that it is a very promising development in diabetes selfmanagement. Lessons learned Specific for diabetes: Integrated in the daily routine of diabetes Non-obtrusive No extra actions on top of obligated procedures, unless: - fun - challenge - rewarding General aspects: Optimal fine-tuning to the targeted age group Full proof and intuitive technology Challenging, but not to difficult game play Stability of all components and connections Performance, speed and game logic must be excellent 9

10 Curricula vitae 10

11 Joseph I. Wolfsdorf MB, BCh Director, Diabetes Program Boston Children s Hospital Chair in Endocrinology Professor of Pediatrics, Harvard Medical School, USA President, International Society of Pediatric and Adolescent Diabetes Is a Professor of Pediatrics at Harvard Medical School and the first incumbent of the Boston Children s Hospital Chair in Endocrinology. Born and educated in South Africa; emigrated to the United States in 1975 where he received training in pediatric endocrinology and metabolism (University of Chicago and Tufts-New England Medical Center, Boston). He is the Director of the Diabetes Program at Boston Children s Hospital. From was Chief of Pediatrics at Joslin Diabetes Center and Medical Director of the Pediatric Diabetes Treatment Unit of the New England Deaconess Hospital. Served as Clinical Chief of the Division of Endocrinology, Boston Children s Hospital from and from Dr. Wolfsdorf is active in the practice of pediatric endocrinology and has a special interest in disorders of carbohydrate metabolism (hypoglycemia, glycogen storage disease) and, especially, the care of children, adolescents and young adults with diabetes mellitus. He has a major interest in the education and training of medical students, pediatric residents, and fellows in pediatric endocrinology, and from directed the Endocrinology and Reproductive Physiology section of the course, Integrated Human Physiology, at Harvard Medical School. Professor Wolfsdorf is an author of 250 publications and has edited and contributed to 5 monographs and books. He currently serves on the editorial board of Diabetes Care and Pediatric Diabetes, is an Associate Editor for Hormone Research in Pediatrics, and is the pediatric endocrinology section editor for UpToDate. Dr. Wolfsdorf contributed to the ESPE/LWPES Consensus Statement on Diabetic Ketoacidosis in children and adolescents, published in 2004, and has been privileged to chair the writing groups responsible for the International Society of Pediatric and Adolescent Diabetes Clinical Practice Guidelines on the management of diabetic ketoacidosis (and hyperglycemic hyperosmolar state) in 2007, 2009, 2014 and 2018 (currently in preparation). He currently serves as the President of the International Society of Pediatric and Adolescent Diabetes (ISPAD). 11

12 Birgit Rami-Merhar MD, Assoc. Professor, MBA University Children s Hospital Medical University of Vienna Austria Medical School: graduation December 1996 (including an elective term at the University of Capetown, RSA 1994) Clin. Training in Pediatrics: at the University Children s Hospital, Univ. Of Vienna/Medical University of Vienna (MUV), for 9 months (Internal Medicine and Surgery) at the Hospital: Barmherzige Brüder, 1020 Vienna Associate Professor of Pediatrics since May 2004 Additional Qualification in Pediatric Endocrinology and Diabetology: March 2007 MBA-Health Care Management: Vienna University of Economics and Business Research: especially in the field of type 1 diabetes mellitus, several national and international cooperations (currently involved in a Horizon2020 EUproject-KidsAP-closed loop in young children) Current research interests: Epidemiology (e.g. EURODIAB), CSII, CGMS, closed loop, quality control projects such as DPV and SWEET, long term prognosis of type 1 diabetes mellitus, complications, psychosocial factors, CHI, ß-cell-functions, Vascular complications in diabetes, insulins, hypoglycaemia Current work: Consultant, Head of the pediatric diabetes outpatient clinic at the MUV, lectures for medical students, research Current position: head of the diabetes outpatient clinic at the Department of Pediatrics, Medical University of Vienna Extras: Medical supervision of 11 diabetes summer camps (2 weeks each) 7 th Cambridge Seminar on Epidemiology & Public Health Aspects of Diabetes Mellitus - Clare College Cambridge July 1999 ESPE summer school, Kazimierz, August 1999 EASD Scientist Training Course, London September 2000 ISPAD Science School December 2000, Berlin Scientific Memberships: EASD, ISPAD, ÖDG, ÖGKJ Current projects: Austrian incidence of type 1 diabetes mellitus < 15 yr EURODIAB-Study Posttransplant-diabetes mellitus Early vascular risk factors in youth with DMT1 DPV-Wiss (Benchmarking) SWEET-Project Horizon KidsAP Psychosocial factors and DMT1 12

13 Thomas Danne Chief Physician, Department of General Pediatrics, Diabetes, Endocrinology & Clinical Research, Diabetes center for Children and Adolescents, Children s Hospital Auf der Bult, Hannover Medical School, Germany. Prof. Dr. Thomas Danne is the Director of the Department of General Pediatrics Endocrinology/Diabetology & Clinical Research at the Auf der Bult Hospital for Children and Adolescents, Hannover Medical School, Germany, which is the largest pediatric diabetes center in Germany. Presently he is appointed as Chairman of the SWEET-project ( and work-package leader of the INNODIA-project ( He is the Past-President of the International Society for Pediatric and Adolescent Diabetes (ISPAD), the German Diabetes Association (DDG) and the German Diabetes Aid (diabetesde). He is a former Research Fellow of the Joslin Diabetes Center of Harvard Medical School in Boston. His research interests include basic and clinical research in diabetology with special emphasis on type 1 diabetes treatment, new insulins, insulin pumps, glucose sensors and the artificial pancreas. Dr. Danne has published over 150 peer reviewed papers is on the Editorial board of several journals and has contributed to several books. 13

14 Gert Jan van der Burg Pediatrician Medical Information Innovation Officer Gelderse Vallei Hospital, The Netherlands Summary of present positions Pediatric diabetologist at Gelderse Vallei Hospital (ZGV), Ede, The Netherlands Medical Information Innovation Officer at Gelderse Vallei Hospital Board member of the Dutch Pediatric Association Member of the Workgroup on Pediatric Diabetes of the Dutch Society of Pediatrics Chairman of the Pediatric Diabetes Cooking Class Foundation Gelderse Vallei Member of the Pediatric Diabetes Cooking Class Foundation Bussum Arbitrator at the Dutch National Health Care Arbitration Tribunal Member of the National committee of Health Care Dispute Resolution Motivational Interviewing Trainer MfN-registered Mediator Education Free University Amsterdam - Medical Education, MD certificate in1983 Free University Hospital, Amsterdam Pediatrics and diabetes, Registration as Pediatrician in 1988 Erasmus University Rotterdam - Health Management INSEAD, France - Health Leadership Programme Centre for Motivation and Change, Hilversum - MI trainers education DialogueBV, Bussum and Rotterdam, Mediator education Present Research Horizon 2020 project PAL (Personal Assistant for a healthy Lifestyle) Enhancing selfmanagement in pediatric diabetes Horizon 2020 project PERGAMON (PERvasive serious GAMes supported by virtual coaching) 14

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16 A. Menarini Diagnostics s.r.l Via Lungo l Ema Bagno a Ripoli, Firenze - Italy