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. 2025 Sep 9.
doi: 10.1007/s00125-025-06536-x. Online ahead of print.

Time below range alone is insufficient to identify severe hypoglycaemia risk in type 1 diabetes-the critical role of hypoglycaemia awareness: results from the SFDT1 study

Dulce Canha  1   2 , Pratik Choudhary  3 , Emmanuel Cosson  4   5 , Isabela Banu  6 , Sara Barraud  7 , René Valéro  8 , Nathalie Ronci  9 , Blandine Delenne  10 , Lise Dufaitre  11 , Tiphaine Vidal-Trecan  12 , Pauline Schaepelynck  13 , Caroline Sanz  14 , Sopio Tatulashvili  4   5 , Gloria A Aguayo  1 , Guy Fagherazzi  15 , Jean-Pierre Riveline  12   16
Affiliations

Time below range alone is insufficient to identify severe hypoglycaemia risk in type 1 diabetes-the critical role of hypoglycaemia awareness: results from the SFDT1 study

Dulce Canha et al. Diabetologia. .

Abstract

Aims/hypothesis: Severe hypoglycaemia events (SHE) remain frequent in people with type 1 diabetes despite advanced diabetes technologies. We examined whether time below range (TBR) 3.9 mmol/l (70 mg/dl; TBR70) or 3.0 mmol/l (54 mg/dl; TBR54) is associated with future SHE risk and whether impaired awareness of hypoglycaemia (IAH) modifies this relationship.

Methods: We analysed data from participants in the Study of the French-speaking Society of Type 1 Diabetes (SFDT1) who used continuous glucose monitoring. IAH was assessed using the Gold Score (≤2, no IAH; 3, undetermined; ≥4, IAH). SHE frequency was self-reported 12 months after inclusion. We analysed associations between TBR and SHE using logistic regression models adjusted for age, sex, social vulnerability and insulin treatment, including TBR-IAH interactions. We performed spline analyses to explore non-linear patterns.

Results: One-year incidence of SHE was 11.7% among 848 participants (mean ± SD age 41.6 ± 13.3 years; 53.8% female sex, HbA1c 57.2 ± 10.9 mmol/mol [7.4 ± 1.0%]). Incidence by TBR70 was 12.1% for ≤1%, 10.2% for 1.1-3.9%, 10.6% for 4-6%, and 14.6% for >6%. Only those with TBR70 >6% and IAH had a significantly higher SHE risk (OR 3.32 [95% CI 1.40, 7.82]) compared with TBR70 ≤1% and no IAH. For TBR54, SHE incidence was 11.0% and 13.3% for categories <1% and ≥1%, respectively. Similarly, only individuals with TBR54≥1% and IAH had increased SHE risk (OR 2.99 [95% CI 1.46, 5.92]). Spline analysis showed low, stable SHE risk across TBR70 values in participants without IAH, with a non-linear pattern only in those with IAH.

Conclusions/interpretation: TBR alone is not discriminative for high-risk SHE but combining TBR with hypoglycaemia awareness status identifies those at the highest risk for both TBR70 and TBR54.

Trial registration: ClinicalTrials.gov NCT04657783.

Keywords: Continuous glucose monitoring; Impaired awareness of hypoglycaemia; Severe hypoglycaemia; Time below range; Type 1 diabetes.

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Conflict of interest statement

Acknowledgements: We would like to express our deepest gratitude to the participants of the SFDT1 study for their valuable contribution. Their participation is essential for the progress of type 1 diabetes-related research. Additionally, we extend our appreciation to the SFDT1 study group for their diligent efforts and dedication to the study. Their collective expertise and commitment have played a critical role in ensuring a high-quality standard for the SFDT1 data. The full list of participating investigators of the SFDT1 study group can be found in the ESM and at https://cohorte-sfdt1.jimdosite.com/ . Parts of this study were presented as oral communications at the 18th International Conference on Advanced Technologies and Treatments for Diabetes, 19–22 March 2025, Amsterdam, the Netherlands, and at the Société Francophone du Diabète congress, 1–4 April 2025, Paris, France. Data availability: Data used for this analysis is available for academic researchers under request submitted to the scientific committee of SFDT1 (cohorte.sfdt1@gmail.com). R scripts created for this analysis are available under request to the corresponding author. Funding: DC is supported by the Luxembourg National Research Fund through grant no. PRIDE21/16749720. This work was made possible thanks to institutional support from the Fondation Francophone pour la Recherche sur le Diabète (FFRD), the Société Francophone du Diabète (SFD) and the Luxembourg Institute of Health, as well as from the following partners: Breakthrough T1D/JDRF; Aide aux Jeunes Diabétiques (AJD); Fédération Française des Diabétiques; Lilly; Abbott; Air Liquide Healthcare; Novo Nordisk; Sanofi; Insulet; Medtronic; Dexcom; Ypsomed; Lifescan; and Sur les Pas de So. The study sponsors/funders were not involved in the design of the study, the collection, analysis and interpretation of data, writing the report, and did not impose any restrictions regarding the publication of the report. For the purpose of open access, and in fulfilment of the obligations arising from the grant agreement, the author has applied a Creative Commons Attribution 4.0 International (CC BY 4.0) license to any Author Accepted Manuscript version arising from this submission. Authors’ relationships and activities: PC has received personal fees from Abbott, Dexcom, Insulet, Medtronic, Ypsomed, Sanofi, Lilly, Roche, Vertex and CML. EC has received grants or contracts from Abbott, AstraZeneca, Novartis, Novo Nordisk, Roche Diagnostics and Sanofi. EC also received consulting fees from Abbott, AlphaDiab, Bayer, AstraZeneca, DexCom, Lilly, LVL Medical, Medtronic, Novartis, Novo Nordisk, Roche Diabetes and Sanofi and received honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbott, Amgen, Bayer, AstraZeneca, Boehringer Ingelheim, Lilly, LVL medical, Medtronic, Novo Nordisk, Roche Diagnostics, Sanofi, Urgo, ViiV Healthcare (GSK) and Roche Diagnostics. EC received support for attending meetings and/or travel from AlphaDiab, Asdia, Lilly, Sanofi and Vitalaire. GF has provided advisory/speaking services for and/or has received research grants and/or speaker honoraria from Sanofi, MSD, MSDAvenir, Eli Lilly, Roche Diabetes Care, AstraZeneca, Danone Research, Diabeloop, Bristol Myers Squibb, L’Oréal R&D, AbbVie Pharmaceutical, Pfizer, Vitalaire and Akuity Care. J-PR received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi Aventis, MSD, Eli Lilly, Novo Nordisk, AstraZeneca, Abbott, Dexcom, AlphaDiab, Medtronic, Air Liquide Santé International and Sanofi. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: PC, J-PR, DC and GF conceptualised the study. DC wrote the first draft of the manuscript. J-PR and EC are the co-principal investigators. DC, GAA, GF, J-PR and EC had full access to the data in the study, verified the data and had full responsibility for the decision to submit and publish. All authors contributed to protocol development and study design. DC and GAA performed the data curation. DC performed the formal analysis. DC, GAA, GF, J-PR, PC and EC wrote the statistical analysis plan (SAP). All authors read the SAP, critically revised it for important intellectual content and approved the final version. All authors read the manuscript, critically revised it for academic content and approved the final version. GF is the guarantor of this work and, as such, has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

References

    1. Ratner RE (2018) Hypoglycemia: new definitions and regulatory implications. Diabetes Technol Ther 20(S2):S250–S253. https://doi.org/10.1089/dia.2018.0113 - DOI - PubMed
    1. Sherr JL, Laffel LM, Liu J et al (2024) Severe hypoglycemia and impaired awareness of hypoglycemia persist in people with type 1 diabetes despite use of diabetes technology: results from a cross-sectional survey. Diabetes Care 47(6):941–947. https://doi.org/10.2337/dc23-1765 - DOI - PubMed - PMC
    1. Lin YK, Ye W, Hepworth E et al (2025) Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort. Diabetologia 68:433–443. https://doi.org/10.1007/s00125-024-06310-5 - DOI - PubMed
    1. Amiel SA (2021) The consequences of hypoglycaemia. Diabetologia 64(5):963–970. https://doi-org.proxy.bnl.lu/10.1007/s00125-020-05366-3
    1. Rossi MC, Nicolucci A, Ozzello A et al (2019) Impact of severe and symptomatic hypoglycemia on quality of life and fear of hypoglycemia in type 1 and type 2 diabetes. Results of the Hypos-1 observational study. Nutr Metab Cardiovasc Dis 29(7):736–743. https://doi.org/10.1016/j.numecd.2019.04.009 - DOI - PubMed

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