Altered Hierarchy of Protective Responses Against Severe Hypoglycemia in Normal Aging in Healthy Men
Abstract
OBJECTIVE: To investigate the effect of normal aging on the protective responses against hypoglycemia, in view of the fact that type II diabetes is primarily a disease of aging, and its treatment is associated with risk of hypoglycemia with cognitive impairment. RESEARCH DESIGN AND METHODS: Plasma glucose was lowered stepwise from 5 to 2.4 mmol/l and restored by manipulation of an infusion of 20% glucose during 220-min intravenous infusion of 1.5 mU · kg−1 · min−1 soluble insulin in 14 men; 7 were aged 60–70 years and the other 7 were 22–26 years. Changes in neurohumoral responses, subjective awareness, and choice reaction time were assessed. RESULTS: Hormonal responses were similar in the two groups, but symptoms began earlier in the younger men (at a plasma glucose of 3.6 ± 0.1 vs. 3.0 ± 0.2 mmol/l, P = 0.02) and were more intense (P = 0.03). Four-choice reaction time, a measure of psychomotor coordination, deteriorated earlier in the older men (at a plasma glucose of 3.0 ± 0.1 vs. 2.6 ± 0.1 mmol/l, P = 0.07) and to a greater degree. The difference between the glucose level for subjective awareness of hypoglycemia and the onset of cognitive dysfunction was lost in the older men (0.0 ± 0.2 vs. 0.8 ± 0.1 mmol/l, P < 0.007). CONCLUSIONS: Older men are prone to more severe cognitive impairment during hypoglycemia than younger men and are less likely to experience prior warning symptoms if blood glucose falls. This effect of normal aging may contribute to the risk of severe hypoglycemia in older diabetic patients treated with sulfonylureas and insulin.
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The glucagon response is almost universally lost within the first few years after type 1 diabetes diagnosis.
“it is almost universally lost within the first few years after diagnosis [14, 15].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [14]
The systematic review's results contrast with the commonly held assumption that the appearance of hypoglycaemic symptoms is hierarchically organised.
“These results contrast with the commonly held assumption that the appearance of hypoglycaemic symptoms is hierarchically organised [13, 14].”
From Glycaemic thresholds for counterregulatory hormone and symptom responses to hypoglycaemia in people with and without type 1 diabetes: a systematic review (2022) · cites this paper as [14]
Age appears to affect counter-regulatory responses to hypoglycemia in non-diabetic individuals.
“Age appears to affect counter-regulatory responses to hypoglycemia in non-diabetic individuals.”
From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [101]
With increasing age, the symptoms of hypoglycemia may become less intense and the symptom profile is modified.
“With increasing age, the symptoms of hypoglycemia may become less intense (12,13) and the symptom profile is modified (9,12,14).”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [13]
In older subjects, symptoms and cognitive dysfunction occurred almost simultaneously at 3.0 ± 0.2 mmol/l (54 ± 4 mg/dl).
“symptoms and cognitive dysfunction occurred almost simultaneously at 3.0 Ϯ 0.2 mmol/l (54 Ϯ 4 mg/dl) in the older subjects (13)”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [13]
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- Authors
- Matyka, K., Evans, M., Lomas, J., Cranston, I., Macdonald, I., & Amiel, S. A.
- Affiliations
- King's College London (GB)
- Queen's Medical Centre (GB)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1997-02-01
- Volume
- 20
- Issue
- 2
- Pages
- 135-141
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2125220286
- Cited by
- 195
- References
- 30
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 9 · 2015: 11 · 2014: 11 · 2013: 9 · 2012: 12
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- 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 › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- hypoglycemia, aging, cognitive impairment, neurohumoral response, reaction time, insulin-induced hypoglycemia, type 2 diabetes, sulfonylureas, older men
- MeSH terms
- Adult, Aged, Aging, Blood Glucose, Blood Pressure, C-Peptide, Cognition, Epinephrine, Glucagon, Heart Rate, Humans, Hydrocortisone, Hypoglycemia, Insulin, Male, Middle Aged, Psychomotor Performance, Glucose Clamp Technique, Cohort Studies, Human Growth Hormone
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