Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort

Yu Kuei Lin¹, Wen Ye², Emily Hepworth³, Annika Agni⁴, Austin M Matus^{5

6}, Anneliese J Flatt^{5

6}, James A M Shaw⁷, Michael R Rickels^{5

6}, Stephanie A Amiel⁸, Jane Speight⁹

Affiliations

¹ Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. yuklin@med.umich.edu.
² Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
³ Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
⁴ Department of Family Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵ Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
⁶ Institute for Diabetes, Obesity & Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
⁷ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
⁸ Department of Diabetes, School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK.
⁹ School of Psychology, Faculty of Health, Deakin University, Geelong, VIC, Australia.

PMID: 39477881
PMCID: PMC11837905
DOI: 10.1007/s00125-024-06310-5

Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort

Yu Kuei Lin et al. Diabetologia. 2025 Feb.

. 2025 Feb;68(2):433-443.

doi: 10.1007/s00125-024-06310-5. Epub 2024 Oct 30.

Authors

Yu Kuei Lin¹, Wen Ye², Emily Hepworth³, Annika Agni⁴, Austin M Matus^{5

6}, Anneliese J Flatt^{5

6}, James A M Shaw⁷, Michael R Rickels^{5

6}, Stephanie A Amiel⁸, Jane Speight⁹

Affiliations

¹ Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA. yuklin@med.umich.edu.
² Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
³ Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
⁴ Department of Family Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵ Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
⁶ Institute for Diabetes, Obesity & Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
⁷ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
⁸ Department of Diabetes, School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, UK.
⁹ School of Psychology, Faculty of Health, Deakin University, Geelong, VIC, Australia.

PMID: 39477881
PMCID: PMC11837905
DOI: 10.1007/s00125-024-06310-5

Abstract

Aims/hypothesis: We aimed to: (1) externally validate the five-item Hypoglycaemia Awareness Questionnaire (HypoA-Q) impaired awareness subscale (HypoA-Q IA); (2) examine how impaired awareness of hypoglycaemia (IAH) relates to the risk of severe hypoglycaemia and level 2 hypoglycaemia; and (3) identify factors associated with IAH.

Methods: Nationwide survey of T1D Exchange registrants was conducted to collect data on demographics, 6 month severe-hypoglycaemia history, hypoglycaemia awareness status (via HypoA-Q IA, the Gold instrument and the Clarke instrument) and continuous glucose monitor (CGM) measures. The Clarke hypoglycaemia awareness factor (Clarke-HAF) was calculated to exclude severe-hypoglycaemia history items. Analyses included Cronbach's α, Spearman correlations and logistic regression.

Results: Valid survey responses were collected from N=1580 adults with type 1 diabetes (median age, 44 years; 52% female participants; median HbA_1c, 48 mmol/mol [6.5%]). Of these, 94% of participants were using CGMs and 69% were using hybrid closed-loop (HCL) systems; 30% had at least one severe-hypoglycaemia episode in the past 6 months. The HypoA-Q IA had satisfactory internal reliability (α=0.79) and construct validity. Higher HypoA-Q IA scores were independently associated with greater risk of severe hypoglycaemia (p<0.001), performing comparably to the Gold instrument and the Clarke-HAF instrument. HypoA-Q IA-determined IAH was independently associated with 88% higher odds of developing severe hypoglycaemia (p<0.001) and twofold higher odds for spending ≥1% of time in level 2 hypoglycaemia (p=0.011). Higher age and longer diabetes duration were associated with higher IAH risk (p<0.001). CGM and HCL use was associated with lower IAH risk (p<0.001).

Conclusions/interpretation: The HypoA-Q IA is a brief, valid and reliable tool for assessing IAH in today's technology-oriented era. IAH was independently associated with severe hypoglycaemia and level 2 hypoglycaemia in a cohort with high prevalence of advanced diabetes technology use and HbA_1c within the recommended range. CGM and HCL use was related to lower IAH risk.

Keywords: Continuous glucose monitors; HypoA-Q; Hypoglycaemia; Impaired awareness of hypoglycaemia; Type 1 diabetes.

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Conflict of interest statement

Acknowledgements: We greatly appreciate the support from the T1D Exchange and all the study participants for completing this study. The study described in the manuscript was accepted for an oral presentation at the 2024 American Diabetes Association Scientific Sessions. Data availability: Data are available on request to YKL (yuklin@med.umich.edu). Funding: This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK129724), and Michigan Center for Clinical and Translational Research (P30DK092926). MRR is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases U01DK135120. REDCap was supported by the National Center for Advancing Translational Sciences (UL1TR00240). Authors' relationships and activities: JS owns the copyright of the HypoA-Q. The other authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: YKL, AMM, AJF, JAMS, MRR, SAA and JS were involved in the conception, design and interpretation of the results. YKL, EH and AA were involved in the data collection. YKL and WY were involved in the analysis. YKL wrote the first draft of the manuscript and is the guarantor of this work. All authors edited, reviewed and approved the final version of the manuscript.

Figures

**Fig. 1**
ROC-AUCs for predicting severe-hypoglycaemia events comparing Gold, Clarke-full, Clarke-HAF and HypoA-Q IA scores. The grey dashed line is a reference line, corresponding to the ROC of a classifier that predicts the class at random

See this image and copyright information in PMC

References

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Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort

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Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort

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