Restoration of Self-Awareness of Hypoglycemia in Adults With Long-Standing Type 1 Diabetes
Open accessAbstract
OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTS: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.
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In type 1 diabetes, the counterregulatory response of epinephrine to hypoglycemia is an important factor for design of glucose control strategies.
“In type 1 diabetes, the counterregulatory response of epinephrine to hypoglycemia is an important factor to be considered for the design of glucose control strategies (34, 35).”
From The progression of secondary diabetes: A review of modeling studies (2022) · cites this paper as [35]
Another study, which focused on assessing the restoration of impaired hypoglycemia awareness and defective hypoglycemia counterregulation through educational strategies over 6 months, observed a significant increase in the mean glucose concentration at which participants first experienced symptoms of hypoglycemia compared to baseline.
“Another study, which focused on assessing the restoration of impaired hypoglycemia awareness and defective hypoglycemia counterregulation through educational strategies over 6 months, observed a significant increase in the mean glucose concentration at which participants first experienced symptoms of hypoglycemia compared to baseline.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [53]
The participants in that study exhibited enhanced counterregulatory responses to hypoglycemia.
“Additionally, the participants exhibited enhanced counterregulatory responses to hypoglycemia [ 53 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [53]
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References 43 · Cited by 56
- Authors
- Leelarathna, L., Little, S. A., Walkinshaw, E., Tan, H. K., Lubina-Solomon, A., Kumareswaran, K., Lane, A. P., Chadwick, T., Marshall, S. M., Speight, J., Flanagan, D., Heller, S. R., Shaw, J. A. M., & Evans, M. L.
- Affiliations
- University of Cambridge (GB)
- Newcastle University (GB)
- University of Sheffield (GB)
- Derriford Hospital (GB)
- Deakin University (AU)
- Corresponding author
- Shaw, James A.M.
- Evans, Mark L.
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2013-11-13
- Volume
- 36
- Issue
- 12
- Pages
- 4063-4070
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC3836150
- OpenAlex
- W2104263154
- Cited by
- 56
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 6 · 2013: 2
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Research Explorer (The University of Manchester) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- National Institute for Health and Care Research (ACF-2013-24-004)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- impaired awareness of hypoglycemia, type 1 diabetes, hypoglycemia counterregulation, continuous glucose monitoring, insulin pump therapy, multiple daily insulin injections, hypoglycemia education, metanephrine, cognitive function, hypoglycemic symptoms, long-standing diabetes, adults with type 1 diabetes
- MeSH terms
- Adult, Awareness, Blood Glucose, Diabetes Mellitus, Type 1, Dose-Response Relationship, Drug, Female, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Male, Middle Aged, Glucose Clamp Technique, Treatment Outcome
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