Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes

Moshe Phillip^{1

2}, Peter Achenbach^{3

4}, Ananta Addala^{5

6}, Anastasia Albanese-O'Neill⁷, Tadej Battelino^{8

9}, Kirstine J Bell¹⁰, Rachel E J Besser^{11

12}, Ezio Bonifacio^{13

14}, Helen M Colhoun^{15

16}, Jennifer J Couper^{17

18

19}, Maria E Craig^{10

20}, Thomas Danne²¹, Carine de Beaufort^{22

23

24}, Klemen Dovc^{8

9}, Kimberly A Driscoll^{25

26

27}, Sanjoy Dutta²⁸, Osagie Ebekozien²⁹, Helena Elding Larsson^{30

31}, Daniel J Feiten³², Brigitte I Frohnert²⁵, Robert A Gabbay³³, Mary P Gallagher³⁴, Carla J Greenbaum³⁵, Kurt J Griffin^{36

37}, William Hagopian³⁸, Michael J Haller^{27

39}, Christel Hendrieckx^{40

41

42}, Emile Hendriks⁴³, Richard I G Holt^{44

45}, Lucille Hughes⁴⁶, Heba M Ismail⁴⁷, Laura M Jacobsen³⁹, Suzanne B Johnson⁴⁸, Leslie E Kolb⁴⁹, Olga Kordonouri²¹, Karin Lange⁵⁰, Robert W Lash⁵¹, Åke Lernmark³⁰, Ingrid Libman⁵², Markus Lundgren^{30

53}, David M Maahs⁵, M Loredana Marcovecchio⁵⁴, Chantal Mathieu⁵⁵, Kellee M Miller²⁹, Holly K O'Donnell²⁵, Tal Oron^{1

2}, Shivajirao P Patil⁵⁶, Rodica Pop-Busui⁵⁷, Marian J Rewers²⁵, Stephen S Rich⁵⁸, Desmond A Schatz⁵⁹, Rifka Schulman-Rosenbaum⁶⁰, Kimber M Simmons²⁵, Emily K Sims⁶¹, Jay S Skyler⁶², Laura B Smith⁶³, Cate Speake³⁵, Andrea K Steck²⁵, Nicholas P B Thomas⁶⁴, Ksenia N Tonyushkina⁶⁵, Riitta Veijola⁶⁶, John M Wentworth^{67

68}, Diane K Wherrett⁶⁹, Jamie R Wood⁷⁰, Anette-Gabriele Ziegler^{3

4}, Linda A DiMeglio⁴⁷

Affiliations

¹ Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
² Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
³ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
⁴ Forschergruppe Diabetes, Technical University Munich, Klinikum Rechts Der Isar, Munich, Germany.
⁵ Division of Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Breakthrough T1D, Gainesville, FL, USA. aaoneill@breakthrought1d.org.
⁸ Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁹ Department of Endocrinology, Diabetes and Metabolism, University Medical Centre Ljubljana, Ljubljana, Slovenia.
¹⁰ Charles Perkins Centre and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
¹¹ JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre Human Genetics, Nuffield Department of Medicine Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
¹² Department of Paediatrics, University of Oxford, Oxford, UK.
¹³ Center for Regenerative Therapies Dresden, Faculty of Medicine, Technical University of Dresden, Dresden, Germany.
¹⁴ Paul Langerhans Institute Dresden, Helmholtz Centre Munich at the University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Dresden, Germany.
¹⁵ The Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
¹⁶ Department of Public Health, NHS Fife, Kirkcaldy, UK.
¹⁷ Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
¹⁸ Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
¹⁹ Division of Paediatrics, Women's and Children's Hospital, Adelaide, SA, Australia.
²⁰ Discipline of Paediatrics & Child Health, School of Clinical Medicine, UNSW Medicine & Health, Sydney, NSW, Australia.
²¹ Breakthrough T1D, Lisbon, Portugal.
²² International Society for Pediatric and Adolescent Diabetes (ISPAD), Berlin, Germany.
²³ Diabetes & Endocrine Care Clinique Pédiatrique (DECCP), Clinique Pédiatrique/Centre Hospitalier (CH) de Luxembourg, Luxembourg City, Luxembourg.
²⁴ Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-Belval, Luxembourg.
²⁵ Department of Pediatrics, Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
²⁶ Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA.
²⁷ Department of Pediatrics, University of Florida Diabetes Institute, Gainesville, FL, USA.
²⁸ Breakthrough T1D, New York, NY, USA.
²⁹ T1D Exchange, Boston, MA, USA.
³⁰ Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
³¹ Department of Pediatrics, Skåne University Hospital, Malmö and Lund, Sweden.
³² Children's Diabetes Foundation, Aurora, CO, USA.
³³ American Diabetes Association, Arlington, VA, USA.
³⁴ NYU Langone Medical Center, New York, NY, USA.
³⁵ Center for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, WA, USA.
³⁶ Sanford Research, Sioux Falls, SD, USA.
³⁷ Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
³⁸ Pacific Northwest Diabetes Research Institute, University of Washington, Seattle, WA, USA.
³⁹ Division of Endocrinology, University of Florida College of Medicine, Gainesville, FL, USA.
⁴⁰ School of Psychology, Deakin University, Geelong, VIC, Australia.
⁴¹ The Australian Centre for Behavioural Research in Diabetes, Diabetes Victoria, Carlton, VIC, Australia.
⁴² Institute for Health Transformation, Deakin University, Geelong, VIC, Australia.
⁴³ Department of Paediatrics, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
⁴⁴ Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
⁴⁵ National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁴⁶ Mount Sinai South Nassau, Oceanside, NY, USA.
⁴⁷ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴⁸ Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL, USA.
⁴⁹ Association of Diabetes Care & Education Specialists, Chicago, IL, USA.
⁵⁰ Medical Psychology, Hannover Medical School, Hannover, Germany.
⁵¹ Endocrine Society, Washington, DC, USA.
⁵² Division of Pediatric Endocrinology and Diabetes, University of Pittsburgh, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
⁵³ Department of Pediatrics, Kristianstad Hospital, Kristianstad, Sweden.
⁵⁴ Department of Pediatrics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁵⁵ Department of Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium.
⁵⁶ Department of Family Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
⁵⁷ Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
⁵⁸ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁵⁹ Department of Pediatrics, University of Florida, Gainesville, FL, USA.
⁶⁰ Division of Endocrinology, Long Island Jewish Medical Center, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, USA.
⁶¹ Division of Pediatric Endocrinology and Diabetology, Herman B Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶² Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
⁶³ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶⁴ NIHR Clinical Research Network Thames Valley and South Midlands, Oxford, UK.
⁶⁵ Division of Endocrinology and Diabetes, Baystate Children's Hospital and University of Massachusetts Chan Medical School - Baystate, Springfield, MA, USA.
⁶⁶ Research Unit of Clinical Medicine, Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
⁶⁷ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁶⁸ Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁶⁹ Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁷⁰ Department of Pediatric Endocrinology, Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

PMID: 38910151
PMCID: PMC11410955
DOI: 10.1007/s00125-024-06205-5

Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes

Moshe Phillip et al. Diabetologia. 2024 Sep.

. 2024 Sep;67(9):1731-1759.

doi: 10.1007/s00125-024-06205-5.

Authors

Affiliations

¹ Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
² Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
³ Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
⁴ Forschergruppe Diabetes, Technical University Munich, Klinikum Rechts Der Isar, Munich, Germany.
⁵ Division of Endocrinology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Breakthrough T1D, Gainesville, FL, USA. aaoneill@breakthrought1d.org.
⁸ Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁹ Department of Endocrinology, Diabetes and Metabolism, University Medical Centre Ljubljana, Ljubljana, Slovenia.
¹⁰ Charles Perkins Centre and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
¹¹ JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre Human Genetics, Nuffield Department of Medicine Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
¹² Department of Paediatrics, University of Oxford, Oxford, UK.
¹³ Center for Regenerative Therapies Dresden, Faculty of Medicine, Technical University of Dresden, Dresden, Germany.
¹⁴ Paul Langerhans Institute Dresden, Helmholtz Centre Munich at the University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Dresden, Germany.
¹⁵ The Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
¹⁶ Department of Public Health, NHS Fife, Kirkcaldy, UK.
¹⁷ Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.
¹⁸ Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
¹⁹ Division of Paediatrics, Women's and Children's Hospital, Adelaide, SA, Australia.
²⁰ Discipline of Paediatrics & Child Health, School of Clinical Medicine, UNSW Medicine & Health, Sydney, NSW, Australia.
²¹ Breakthrough T1D, Lisbon, Portugal.
²² International Society for Pediatric and Adolescent Diabetes (ISPAD), Berlin, Germany.
²³ Diabetes & Endocrine Care Clinique Pédiatrique (DECCP), Clinique Pédiatrique/Centre Hospitalier (CH) de Luxembourg, Luxembourg City, Luxembourg.
²⁴ Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-Belval, Luxembourg.
²⁵ Department of Pediatrics, Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
²⁶ Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA.
²⁷ Department of Pediatrics, University of Florida Diabetes Institute, Gainesville, FL, USA.
²⁸ Breakthrough T1D, New York, NY, USA.
²⁹ T1D Exchange, Boston, MA, USA.
³⁰ Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
³¹ Department of Pediatrics, Skåne University Hospital, Malmö and Lund, Sweden.
³² Children's Diabetes Foundation, Aurora, CO, USA.
³³ American Diabetes Association, Arlington, VA, USA.
³⁴ NYU Langone Medical Center, New York, NY, USA.
³⁵ Center for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, WA, USA.
³⁶ Sanford Research, Sioux Falls, SD, USA.
³⁷ Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
³⁸ Pacific Northwest Diabetes Research Institute, University of Washington, Seattle, WA, USA.
³⁹ Division of Endocrinology, University of Florida College of Medicine, Gainesville, FL, USA.
⁴⁰ School of Psychology, Deakin University, Geelong, VIC, Australia.
⁴¹ The Australian Centre for Behavioural Research in Diabetes, Diabetes Victoria, Carlton, VIC, Australia.
⁴² Institute for Health Transformation, Deakin University, Geelong, VIC, Australia.
⁴³ Department of Paediatrics, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
⁴⁴ Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
⁴⁵ National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁴⁶ Mount Sinai South Nassau, Oceanside, NY, USA.
⁴⁷ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴⁸ Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL, USA.
⁴⁹ Association of Diabetes Care & Education Specialists, Chicago, IL, USA.
⁵⁰ Medical Psychology, Hannover Medical School, Hannover, Germany.
⁵¹ Endocrine Society, Washington, DC, USA.
⁵² Division of Pediatric Endocrinology and Diabetes, University of Pittsburgh, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
⁵³ Department of Pediatrics, Kristianstad Hospital, Kristianstad, Sweden.
⁵⁴ Department of Pediatrics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁵⁵ Department of Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium.
⁵⁶ Department of Family Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
⁵⁷ Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
⁵⁸ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁵⁹ Department of Pediatrics, University of Florida, Gainesville, FL, USA.
⁶⁰ Division of Endocrinology, Long Island Jewish Medical Center, Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, USA.
⁶¹ Division of Pediatric Endocrinology and Diabetology, Herman B Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶² Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
⁶³ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶⁴ NIHR Clinical Research Network Thames Valley and South Midlands, Oxford, UK.
⁶⁵ Division of Endocrinology and Diabetes, Baystate Children's Hospital and University of Massachusetts Chan Medical School - Baystate, Springfield, MA, USA.
⁶⁶ Research Unit of Clinical Medicine, Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
⁶⁷ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
⁶⁸ Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, VIC, Australia.
⁶⁹ Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁷⁰ Department of Pediatric Endocrinology, Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

PMID: 38910151
PMCID: PMC11410955
DOI: 10.1007/s00125-024-06205-5

Erratum in

Correction to: Consensus guidance for monitoring individuals with islet autoantibody‑positive pre‑stage 3 type 1 diabetes.
Phillip M, Achenbach P, Addala A, Albanese-O'Neill A, Battelino T, Bell KJ, Besser REJ, Bonifacio E, Colhoun HM, Couper JJ, Craig ME, Danne T, de Beaufort C, Dovc K, Driscoll KA, Dutta S, Ebekozien O, Larsson HE, Feiten DJ, Frohnert BI, Gabbay RA, Gallagher MP, Greenbaum CJ, Griffin KJ, Hagopian W, Haller MJ, Hendrieckx C, Hendriks E, Holt RIG, Hughes L, Ismail HM, Jacobsen LM, Johnson SB, Kolb LE, Kordonouri O, Lange K, Lash RW, Lernmark Å, Libman I, Lundgren M, Maahs DM, Marcovecchio ML, Mathieu C, Miller KM, O'Donnell HK, Oron T, Patil SP, Pop-Busui R, Rewers MJ, Rich SS, Schatz DA, Schulman-Rosenbaum R, Simmons KM, Sims EK, Skyler JS, Smith LB, Speake C, Steck AK, Thomas NPB, Tonyushkina KN, Veijola R, Wentworth JM, Wherrett DK, Wood JR, Ziegler AG, DiMeglio LA. Phillip M, et al. Diabetologia. 2024 Sep;67(9):2012-2014. doi: 10.1007/s00125-024-06266-6. Diabetologia. 2024. PMID: 39230637 Free PMC article. No abstract available.

Abstract

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb⁺) children and adults who are at risk of (confirmed single IAb⁺) or living with (multiple IAb⁺) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb⁺; (2) when people who are IAb⁺ are initially identified there is a need for confirmation using a second sample; (3) single IAb⁺ individuals are at lower risk of progression than multiple IAb⁺ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

Keywords: Autoantibodies; Glucose monitoring; Prevention; Type 1 diabetes.

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Figures

**Fig. 1**
Algorithm for monitoring of people screened positive for one or more islet autoantibodies. ^aMonitoring frequency and methodology depends on age, length of time since first detection of islet autoantibody, number of islet autoantibodies detected and presence of symptoms of type 1 diabetes (see Tables 1, 3, 4 and 5). Ab, antibody; GP, general practitioner; PRN, pro re nata (as needed); Sx, symptoms; T1D, type 1 diabetes. This figure is available as part of a downloadable slideset

**Fig. 2**
The continuum of educational needs and competencies: what does one need to know? The image represents the anticipated skills that must be developed within the continuum of stakeholders in monitoring presymptomatic type 1 diabetes. The groups indicated within the pyramid sections should have the competencies described and participate as appropriate. The need is for unified, consistent, globally applicable language at all levels. T1D, type 1 diabetes. This figure is available as part of a downloadable slideset

See this image and copyright information in PMC

References

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1. Riley WJ, Atkinson MA, Schatz DA, Maclaren NK (1990) Comparison of islet autoantibodies in ‘pre-diabetes’ and recommendations for screening. J Autoimmun 3:47–51. 10.1016/S0896-8411(09)90009-9 - PubMed
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1. American Diabetes Association Professional Practice Committee (2024) 3. Prevention or delay of diabetes and associated comorbidities: standards of care in diabetes—2024. Diabetes Care 47(Supplement_1):S43–S51. 10.2337/dc24-S003 - PMC - PubMed
1. TEDDY Study Group (2008) The Environmental Determinants of Diabetes in the Young (TEDDY) study. Ann N Y Acad Sci 1150:1–13. 10.1196/annals.1447.062 - PMC - PubMed

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Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes

Affiliations

Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes

Authors

Affiliations

Erratum in

Abstract

Figures

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical