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European Association for the Study of Diabetes Scientific update

Autoimmune type 1 diabetes: Can we see it coming?
 

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Video: Hypo-RESOLVE: Why does hypoglycemia research remain important?

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Guess what: PWT1D can also get CKD

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Technology: What is happening in the field of diabetes?

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Video: Impressions from your colleagues

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Thank you EASD 2023 Change in the field of diabetes

The European Association for the Study of Diabetes (EASD) recently organized the 59th edition of the congress in Hamburg, Germany. Experts, researchers, and healthcare professionals dedicated to advancing the understanding of diabetes, came together to present, discuss, and celebrate the advancements and innovations to improve diabetes management and the quality of live for people living with diabetes. In this newsletter you will find a selection of key highlights of the congress.

Once again, a consensus was reached during this congress. Indeed, everyone agreed that this edition of the EASD was a very special one: a wind of change and hope blew over our heads, with a huge number of sessions focusing directly or indirectly on the new possibilities for detecting and preventing the various stages of T1DM. In addition, new technologies (AI, artificial pancreas) and transplants were also presented.

Finally, another special feature of the conference, noted by our colleagues living with diabetes, was the way in which the debate focused on the individual, their needs, concerns and objectives to improve diabetes management in a tailor-made manner.

In the presidential address, Prof. Mathieu started by celebrating this year’s congress and emphasized that this is an important and exciting juncture for research in the field of diabetes. New therapies, new insights in diabetes and diabetes management for both type 1 and type 2, the impact of nutrition and new technologies and interventions are reshaping the field.

Finally, the new logo of EASD was announced with the emphasis that EASD stands for innovation, excellence, collaboration in research, inclusivity, diversity, and sustainability. EASD supports diabetes research, promotes excellence, and disseminates knowledge. This goes hand in hand with initiatives such as guidelines, the European Diabetes Forum, and listening to the voices of people living with diabetes and ending the stigma associated with diabetes.

Autoimmune type 1 diabetes Can we see it coming?

During the Claude Bernard lecture, prize laureate prof. Ake Lernmark from Lund university discussed his carrier path on unveiling the etiology of autoimmune type 1 diabetes, and the importance of identifying biomarkers of progression to develop effective screening strategies.

First, HLA DQ typing could allow for newborn screening since 94% of children diagnosed with T1D bare the DQ2 and/or DQ8 types3,7. However, the detection of beta-cell specific autoantibodies (Aabs) allows for staging of T1D. The author highlighted the fact that there is a timeline in the appearance of the different islet Aabs in the development of the disease and that the presence of each Aab is associated with different levels of risk3,4.

The speaker further mentioned that increases in HbA1c within the normal range were also markers of risk to develop T1D1,2.

Interestingly, inflammatory biomarkers appear to precede insulin and GAD65 auto-antibody appearance.

Finally, viral infections affect auto-antibody appearance as well. Indeed, deficient anti-viral immune response has been identified in children presenting positive islet Aabs. Moreover, an RCT published this year in Nature medicine showed that, in children with newly diagnosed T1D, treatment with pleconaril and riboflavin reduces the decline of C-peptide at 12 months after diagnosis8.

The causal link between the suboptimal anti-viral response and the development of autoimmunity remains to be unveiled5,6. In the same line of thought, during the Albert Renold lecture, prof. Yuval Dor suggested a potential link between RNA editing and type 1 diabetes9. His team explores how the deficiency of RNA editing in beta cells can lead to inflammation and immune (IFN) responses that contribute to the development of diabetes.

Schematic illustrating RNA editing of immunogenic dsRNAs bridges the gap between risk variants and susceptibility of autoimmune and immune-related diseases. Adapted from Li et al, 2022.9

What does it mean in practice? 

In a Sanofi sponsored symposium, Dr. Besser (Oxford university, UK) discussed implementing best practices for T1D management. As a pediatrician, she called for T1D Aabs screening for the following reasons: 

  • Prevent DKA and associated morbidity and mortality. 
  • Prepare people and their families for insulin therapy. 
  • Offer available preventative therapies through clinical practice or trial recruitment. 

Dr. Besser particularly highlighted the robust evidence that screening significantly helps reduce DKA at time of diagnosis10. She also advised screening children at the ages of two and six, as suggested from published data11. Finally, Dr. Besser reminded us to use the 2022 ISPAD Clinical Practice Consensus Guidelines which encourage general population screening programs with level A evidence12.  

Video Hypo-RESOLVE: Why does hypoglycemia research remain important?

The latest updates on hypoglycemia research were also presented, including the results from the Hypo-RESOLVE consortium. This project, led by Prof. Bastiaan de Galan (Maastricht and Radboud University Medical Center) is an ambitious European project started in 2018 to advance the understanding of hypoglycaemia to reduce the burden and consequences of hypoglycaemia among people with diabetes. The commentary by Prof. Brian F. Frier (University of Edinburgh) nicely puts the project in context by looking back on “a decade of hypoglycemia research”. He mentions that research has indeed come a long way; focusing on the clinical manifestations by a select few during the first 50 years or so to now being the primary study outcome in clinical trials of new drugs.

Watch this video below to hear why Dr. Elina Pimiä (Tampere Diabetes Outpatient Clinic), found this to be a key session to follow.

Guess what PWT1D can also get CKD

In an evening session moderated by Dr. Peter Rossing (Steno Diabetes Center Copenhagen), Dr. Katherine Tuttle (University of Washington) and Dr. Hiddo Heerspink (University Medical Center Groningen) highlighted the unmet needs regarding chronic kidney disease (CKD) in people with T1D.

Dr. Rossing opened the session by showing that the majority of CKD studies are in populations without diabetes or with T2D; the last successful T1D trial having been conducted in 1993.13 

Dr. Tuttle addressed the epidemiology of CKD in T1D. According to CURE-CKD based data, the overall prevalence of CKD in the US population very likely or likely to have T1D is 28%, which has increased over time across all age groups. CKD prevalence was found to increase with age in people with T1D, especially for people ≥60 years of age.14

Dr. Heerspink reviewed ongoing trials that are looking for a new indication for the treatment of T1D and CKD. He explained that one of the major limitations in carrying out clinical trials in T1D is the lack of feasible clinical endpoints. Considering this, he went on to name albuminuria as a promising bridging endpoint to predict the efficacy of therapeutic intervention. His team is currently conducting FINE-ONE, a global phase 3 trial which assesses finerenone in T1D.15 

Dr. Heerspink was optimistic that other trials such as ASPIRE (Study Details | Anticoagulation in ICH Survivors for Stroke Prevention and Recovery | ClinicalTrials.gov) will provide more information about efficacy and safety of various therapeutics for CKD in T1D such as a combination of SGLT-2s and endothelin receptor antagonist (ERA).

EASD Technology

Smart pens for smart decisions

Peter Adolfsson discussed during the session “Many Digits in Digital Diabetes” the results of a real-world study that introduced smart connected insulin pens to people living with type 1 diabetes on MDI therapy. 

The study showed that using these smart pens, primarily for bolus insulin administration, led to improved glycemic control. The improvements included increased time in range and reductions in time below and time above range. A diverse population of individuals using CGM was included in this study. Subgroup analyses revealed that even those with the lowest baseline time in range experienced significant improvements. The results suggest that the introduction of smart insulin pens can be a valuable tool for enhancing diabetes management and achieving better glycemic control when reliable insulin dose data contributes to insulin management in people with T1D.16

AID systems vs. islet transplantation: Who wins the fight? 
In the session “Beyond Technology to Physiological Solutions for Type 1 Diabetes - The Case for Islet Cell Replacement”, automated insulin delivery systems (AID) and their algorithms were discussed and compared to islet cell replacement therapy. AID systems combine control algorithms (often powered by artificial intelligence), CGM sensors, and insulin pumps to automate dosing decisions for people with diabetes. 

There are both commercial and open-source AID systems available. When comparing commercial and open-source AID systems through real-world studies, both types show lower HbA1c levels after a few months of use and an increase of the time in range. Hypoglycemia rates remain stable. However, substantial variations exist in the day-to-day experiences of users with the different AID systems. The key factor in these variations is the human factor, emphasizing the critical role of individual preferences and the need to determine the most suitable AID system for a specific person living with diabetes. Commercial and open-source AID systems offer advantages like lower costs, accessibility, easier to apply and no need for immunosuppression.17

AID systems and islet transplantation are both not a cure for diabetes but effective treatment options. Islet cell transplantation is a biological approach that can lead to better clinical outcomes, more time in range, fewer oscillations, and less hypoglycemia risk. A drawback is that 48% of the people after one year still need low doses of insulin in the phase 3 trial of transplantation of human islets in T1D complicated by severe hypoglycemia.18 

The human factor plays a key role. When assessing the types of AID systems or islet transplantation. Factors like lived experiences, technological issues, and the impact on daily life can influence an individual's decision to use these systems. Both islet cell transplants and automated insulin delivery (AID) systems show considerable promise in improving the lives of individuals with diabetes.19

Will artificial intelligence take over?

During the session on “Artificial Intelligence in Diabetes Care: Potential and Concerns” Dr. Philip Moshe presented the findings of the ADVICE4U study on the role of artificial intelligence-based decision support systems (AI-DSS) in diabetes management. This study aimed to determine whether insulin dose adjustments guided by an AI-DSS are as effective and safe as those guided by physicians in managing glucose levels in individuals with type 1 diabetes. For patients not using GGM or closed-loop systems, AI-driven decision support systems offer guidance on insulin dosing and lifestyle adjustments.

The results showed that the AI system was statistically non-inferior to physician guidance in maintaining TIR (50.2 ± 11.1% versus 51.6 ± 11.3%). Additionally, the TBR < 54 mg/dl was statistically non-inferior of the AI-group compared to the physician treated group. This study underlines the potential of AI in optimizing insulin therapy for individuals with type 1 diabetes, offering a safe and effective alternative to traditional physician management.20

Video Impressions from your colleagues

References

  1.    Salami F, Tamura R, You L, et al. HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children. Pediatr Diabetes. 2022;23(8):1586-1593. doi:10.1111/pedi.13413 
  2.     Vehik K, Boulware D, Killian M, et al. Rising Hemoglobin A1c in the Nondiabetic Range Predicts Progression of Type 1 Diabetes As Well As Oral Glucose Tolerance Tests. Diabetes Care. 2022;45(10):2342-2349. doi:10.2337/dc22-0828 
  3.     Kwon BC, Anand V, Achenbach P, et al. Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories. Nat Commun. 2022;13(1):1514. Published 2022 Mar 21. doi:10.1038/s41467-022-28909-1 
  4.     Krischer JP, Liu X, Lernmark Å, et al. Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study. Diabetes Care. 2022;45(10):2271-2281. doi:10.2337/dc21-2612 
  5.     Vehik K, Lynch KF, Wong MC, et al. Prospective virome analyses in young children at increased genetic risk for type 1 diabetes. Nat Med. 2019;25(12):1865-1872. doi:10.1038/s41591-019-0667-0 
  6.     Ferrat LA, Vehik K, Sharp SA, et al. A combined risk score enhances prediction of type 1 diabetes among susceptible children [published correction appears in Nat Med. 2022 Mar;28(3):599]. Nat Med. 2020;26(8):1247-1255. doi:10.1038/s41591-020-0930-4 
  7.     Zhao LP, Papadopoulos GK, Kwok WW, et al. Next-Generation HLA Sequence Analysis Uncovers Seven HLA-DQ Amino Acid Residues and Six Motifs Resistant to Childhood Type 1 Diabetes. Diabetes. 2020;69(11):2523-2535. doi:10.2337/db20-0374 
  8.     Krogvold L, Mynarek IM, Ponzi E, et al. Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial [published online ahead of print, 2023 Oct 4]. Nat Med. 2023;10.1038/s41591-023-02576-1. doi:10.1038/s41591-023-02576-1
  9.     Li Q, Gloudemans MJ, Geisinger JM, et al. RNA editing underlies genetic risk of common inflammatory diseases. Nature. 2022;608(7923):569-577. doi:10.1038/s41586-022-05052-x
  10.     Hummel S, Carl J, Friedl N, et al. Children diagnosed with presymptomatic type 1 diabetes through public health screening have milder diabetes at clinical manifestation. Diabetologia. 2023;66(9):1633-1642. doi:10.1007/s00125-023-05953-0
  11.     Simmons K, Frohnert B, O'Donnell H, et al. Historical Insights and Current Perspectives on the Diagnosis and Management of Pre-Symptomatic Type 1 Diabetes [published online ahead of print, 2023 Sep 11]. Diabetes Technol Ther. 2023;10.1089/dia.2023.0276. doi:10.1089/dia.2023.0276
  12.     Besser REJ, Bell KJ, Couper JJ, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2022;23(8):1175-1187. doi:10.1111/pedi.13410
  13.     Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group [published correction appears in N Engl J Med 1993 Jan 13;330(2):152]. N Engl J Med. 1993;329(20):1456-1462. doi:10.1056/NEJM199311113292004
  14.     Tuttle KR, Jones CR, Daratha KB, et al. Incidence of Chronic Kidney Disease among Adults with Diabetes, 2015-2020. N Engl J Med. 2022;387(15):1430-1431. doi:10.1056/NEJMc2207018
  15.     Heerspink HJL, Birkenfeld AL, Cherney DZI, et al. Rationale and design of a randomised phase III registration trial investigating finerenone in participants with type 1 diabetes and chronic kidney disease: The FINE-ONE trial [published online ahead of print, 2023 Sep 14]. Diabetes Res Clin Pract. 2023;110908. doi:10.1016/j.diabres.2023.110908
  16.     Adolfsson, P., Hartvig, N. V., Kaas, A., Møller, J. B., & Hellman, J. (2020). Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen. Diabetes technology & therapeutics, 22(10), 709–718. https://doi.org/10.1089/dia.2019.0411
  17.     Knoll, C., Peacock, S., Wäldchen, M., Cooper, D., Aulakh, S. K., Raile, K., Hussain, S., & Braune, K. (2022). Real-world evidence on clinical outcomes of people with type 1 diabetes using open-source and commercial automated insulin dosing systems: A systematic review. Diabetic medicine : a journal of the British Diabetic Association, 39(5), e14741. https://doi.org/10.1111/dme.14741
  18.     Hering, B. J., Clarke, W. R., Bridges, N. D., Eggerman, T. L., Alejandro, R., Bellin, M. D., Chaloner, K., Czarniecki, C. W., Goldstein, J. S., Hunsicker, L. G., Kaufman, D. B., Korsgren, O., Larsen, C. P., Luo, X., Markmann, J. F., Naji, A., Oberholzer, J., Posselt, A. M., Rickels, M. R., Ricordi, C., … Clinical Islet Transplantation Consortium (2016). Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes care, 39(7), 1230–1240. https://doi.org/10.2337/dc15-1988
  19.     Latres, E., Finan, D. A., Greenstein, J. L., Kowalski, A., & Kieffer, T. J. (2019). Navigating Two Roads to Glucose Normalization in Diabetes: Automated Insulin Delivery Devices and Cell Therapy. Cell metabolism, 29(3), 545–563. https://doi.org/10.1016/j.cmet.2019.02.007
  20.     Nimri, R., Battelino, T., Laffel, L. M., Slover, R. H., Schatz, D., Weinzimer, S. A., Dovc, K., Danne, T., Phillip, M., & NextDREAM Consortium (2020). Insulin dose optimization using an automated artificial intelligence-based decision support system in youths with type 1 diabetes. Nature medicine, 26(9), 1380–1384. https://doi.org/10.1038/s41591-020-1045-7
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