Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes
Open accessAbstract
OBJECTIVE Older patients with type 2 diabetes are at a particularly high risk for severe hypoglycemic episodes, and experimental studies in healthy subjects hint at a reduced awareness of hypoglycemia in aged humans. However, subjective responses to hypoglycemia have rarely been assessed in older type 2 diabetic patients. RESEARCH DESIGN AND METHODS We tested hormonal, subjective, and cognitive responses (reaction time) to 30-min steady-state hypoglycemia at a level of 2.8 mmol/l in 13 older (> or =65 years) and 13 middle-aged (39-64 years) type 2 diabetic patients. RESULTS Hormonal counterregulatory responses to hypoglycemia did not differ between older and middle-aged patients. In contrast, middle-aged patients showed a pronounced increase in autonomic and neuroglycopenic symptom scores at the end of the hypoglycemic plateau that was not observed in older patients (both P < 0.01). Also, seven middle-aged patients, but only one older participant, correctly estimated their blood glucose concentration to be <3.3 mmol/l during hypoglycemia (P = 0.011). A profound prolongation of reaction times induced by hypoglycemia in both groups persisted even after 30 min of subsequent euglycemia. CONCLUSIONS Our data indicate marked subjective unawareness of hypoglycemia in older type 2 diabetic patients that does not depend on altered neuroendocrine counterregulation and may contribute to the increased probability of severe hypoglycemia frequently reported in these patients. The joint occurrence of hypoglycemia unawareness and deteriorated cognitive function is a critical factor to be carefully considered in the treatment of older patients.
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Prevalence of diabetic retinopathy decreases with increasing TIR.
“Results showed that individuals with more advanced DR spent significantly less time within target (70-180 mg/dL [3.9-10.0 mmol/L) and that prevalence of DR decreased with increasing TIR.”
From Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019) · cites this paper as [52]
The Research Design and Methods and Results sections describe a hypoglycemic-clamp study comparing older and middle-aged patients, not an analysis of diabetic retinopathy. Searches for retinopathy, time in range (TIR), and the 70–180 mg/dL target found no passage addressing the claimed relationship. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn 3,262 individuals with type 2 diabetes, more advanced diabetic retinopathy is associated with less time in target range.
“Results showed that individuals with more advanced DR spent significantly less time within target (70-180 mg/dL [3.9-10.0 mmol/L) and that prevalence of DR decreased with increasing TIR.”
From Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019) · cites this paper as [52]
The Research Design and Methods section describes a hypoglycemic-clamp experiment in 26 patients, not a study of 3,262 individuals. Searches for diabetic retinopathy and time in range found no passage addressing their association; the paper’s Results concern responses to hypoglycemia. (LLM, conf=0.78)
Experimental — accuracy not yet measuredTIR (70-180 mg/dL) correlates with diabetes complications.
“However, there is evidence from a number of recent studies that have shown correlations of TIR (70-180 mg/dL [3.9-10.0 mmol/L]) with diabetes complications (52; 53)”
From Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019) · cites this paper as [52]
The Research Design and Methods section describes a hypoglycemic-clamp study and says participants had no clinical evidence of diabetes complications. The Results report responses to hypoglycemia, not time in range or its correlation with complications. Searches for TIR, the 70–180 mg/dL range, and complications found no passage addressing the claimed correlation; page numbers were unavailable. (LLM, conf=0.78)
Experimental — accuracy not yet measuredIn one small study, hormonal counter-regulatory responses to hypoglycemia did not differ between older (mean age 70 years) and middle-aged (mean 51 years) people with type 2 diabetes.
“One small study compared responses to hypoglycemic clamps in older (mean age 70 years) vs. middle-aged (mean 51 years) people with type 2 diabetes. Hormonal counter-regulatory responses to hypoglycemia did not differ between age groups, but middle-aged participants had a significant increase in autonomic and neuroglycopenic symptoms at the end of the hypoglycemic period, while older participants”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [102]
In the same study, middle-aged participants had a significant increase in autonomic and neuroglycopenic symptoms at the end of the hypoglycemic period, while older participants did not.
“Hormonal counter-regulatory responses to hypoglycemia did not differ between age groups, but middle-aged participants had a significant increase in autonomic and neuroglycopenic symptoms at the end of the hypoglycemic period, while older participants did not.”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [102]
In the same study, half of middle-aged, but only 1/13 older participants, correctly reported that their blood glucose was low during hypoglycemia.
“Half of middle-aged, but only 1/13 older participants, correctly reported that their blood glucose was low during hypoglycemia102.”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [102]
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References 11 · Cited by 298
- Authors
- Bremer, J. P., Jauch-Chara, K., Hallschmid, M., Schmid, S., & Schultes, B.
- Affiliations
- University of Lübeck (DE)
- Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany;
- Kantonsspital St. Gallen (CH)
- Corresponding author
- Schultes, Bernd
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2009-06-01
- Volume
- 32
- Issue
- 8
- Pages
- 1513-1517
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2713637
- OpenAlex
- W2010534563
- Cited by
- 298
- References
- 11
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 10 · 2023: 12 · 2022: 15 · 2021: 16 · 2020: 17 · 2019: 21 · 2018: 25 · 2017: 19 · 2016: 20 · 2015: 22 · 2014: 25 · 2013: 20 · 2012: 19
- FWCI
- 12.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
- Keywords
- hypoglycemia unawareness, type 2 diabetes, older adults, age differences, counterregulatory hormones, neuroglycopenic symptoms, autonomic symptoms, blood glucose estimation, reaction time, cognitive impairment, severe hypoglycemia
- MeSH terms
- Adrenocorticotropic Hormone, Adult, Aged, Aged, 80 and over, Awareness, Blood Glucose, Cognition, Cognition Disorders, Diabetes Mellitus, Type 2, Epinephrine, Female, Glucagon, Humans, Hydrocortisone, Hypoglycemia, Male, Middle Aged, Norepinephrine, Reaction Time, Sensory Thresholds, Growth Hormone
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