Counterregulatory hormone responses to hypoglycemia in the elderly patient with diabetes
Abstract
In patients with non-insulin-dependent diabetes mellitus (NIDDM), the risk of severe or fatal hypoglycemia associated with the use of oral agents or insulin increases exponentially with age. We conducted this study with the hypothesis that this increased susceptibility to hypoglycemia is caused by alterations in release of counterregulatory hormones and psychomotor performance during hypoglycemia. Ten healthy nonobese elderly subjects (74 ± 1 years of age; body mass index, 24.5 ± 0.6 kg/m2) and 10 nonobese elderly NIDDM subjects (72 ± 1 years of age; body mass index, 25.6 ± 0.9 kg/m2) underwent two hyperinsulinemic glucose clamp studies (insulin infusion, 60 mU·m₋2 · min₋1). In the control study, glucose was maintained at 5 mM for 5 h; in the hypoglycemic study, glucose was kept at 5 mM for 1 h and then lowered in a stepwise fashion to 4.4, 3.8, 3.3, and 2.8 mM in each subsequent hour. At regular intervals in each study, neuropsychological tests were performed, counterregulatory hormones were measured, and a hypoglycemic symptom questionnaire was administered. At a glucose level of 2.8 mM, NIDDM patients had reduced incremental glucagon (normal subjects, 114 ± 18 ng/l; NIDDM subjects, 63 ± 9 ng/l; P < 0.05) and growth hormone responses (normal subjects, 13.8 ± 1.0 micrograms/l; NIDDM subjects, 7.0 ± 2.0 micrograms/l; P < 0.01) and increased epinephrine (normal subjects, 925 ± 198 pM; NIDDM subjects, 4175 ± 824 pM; P < 0.001) and cortisol responses (normal subjects, 291 ± 49 nM; NIDDM subjects, 524 ± 92 mM; P < 0.05). Symptom scores were similar in both groups at all levels of glycemia. at all levels of glycemia. At a glucose level of 2.8 mM, NIDDM patients had a greater impairment on the simple (normal subjects, ₋ 10 ± 24 ms; NIDDM subjects, 108 ± 18 ms; P < 0.001) and choice (normal subjects, 20 ± 18 ms; NIDDM subjects, 111 ± 18 ms; P < 0.01) reaction time tests. We conclude that the elderly NIDDM patients have altered release of counterregulatory hormones and altered psychomotor performance during hypoglycemia.
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Symptomatic responses to hypoglycemia were similar in elderly people with and without type 2 diabetes, suggesting that decreased symptom intensity is associated with increasing age independent of diabetes.
“A further study (16) by the same group reported that symptomatic responses were similar in 10 elderly people with (7 male, aged 72 Ϯ 1 years) and 10 without (6 male, aged 74 Ϯ 1 years) type 2 diabetes, suggesting that the decreased symptom intensity observed in their first study was associated with increasing age, independent of any effects of diabetes.”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [16]
Most investigators reporting preservation of the glucagon response have studied people with type 2 diabetes who were unlikely to be insulin deficient, and, with one exception, all of these studies have examined counterregulatory responses in middle-aged subjects in their 5th or 6th decade.
“Most investigators reporting preservation of the glucagon response have studied people with type 2 diabetes who were unlikely to be insulin deficient (33,34,36,38), and, with one exception (16), all of these studies have examined counterregulatory responses in middle-aged subjects in their 5th or 6th decade.”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [16]
In type 2 diabetes, the glucagon response to hypoglycemia has been diversely reported as being either modestly diminished or preserved.
“In type 2 diabetes, the glucagon response to hypoglycemia has been diversely reported as being either modestly diminished (16, 30,50) or preserved (33,34,37,38).”
From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [16]
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Self-citation[Hypoglycemia in the elderly with diabetes mellitus].
Fematt, F. M. Á., & Montaña‐Álvarez, M. (2010) · PubMed · Cited by 14 · see citing works
Au, N. H., Ratzki-Leewing, A., Zou, G., Ryan, B. L., Webster-Bogaert, S., Reichert, S. M., Brown, J. B., & Harris, S. B. (2022) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2021.09.004 · Cited by 14 · see citing works
Perioperative Glucose Control and Infection Risk in Older Surgical Patients
Lee, P., Min, L. C., & Mody, L. (2014) · Current Geriatrics Reports · doi:10.1007/s13670-014-0077-6 · Cited by 14 · see citing works
Antecedent Hypoglycemia Does Not Attenuate the Acceleration of Gastric Emptying by Hypoglycemia
Kar, P., Jones, K. L., Plummer, M. P., Abdelhamid, Y. A., Giersch, E. J., Summers, M. J., Hatzinikolas, S., Heller, S. R., Horowitz, M., & Deane, A. M. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00051 · Cited by 14 · see citing works
Drug treatment for diabetes in nursing home residents
Barreto, P. D. S., Sanz, C., Vellas, B. J., Lapeyre‐Mestre, M., & Rolland, Y. (2013) · Diabetic Medicine · doi:10.1111/dme.12354 · Cited by 13 · see citing works
- Authors
- Meneilly, G. S., Cheung, E., & Tuokko, H.
- Affiliations
- University of British Columbia Hospital (CA)
- ORCID
- Meneilly, G. S.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1994-03-01
- Volume
- 43
- Issue
- 3
- Pages
- 403-410
- ISSN
- 0012-1797 (ISSN-L)
- OpenAlex
- W1965068312
- Cited by
- 167
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 11 · 2016: 7 · 2015: 11 · 2014: 6 · 2013: 10 · 2012: 6
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council Canada
- 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, counterregulatory hormones, type 2 diabetes, elderly patients, glucagon, growth hormone, epinephrine, cortisol, psychomotor performance, hypoglycemic symptoms, hyperinsulinemic-euglycemic clamp, oral antidiabetic drugs, insulin therapy
- MeSH terms
- Aged, Diabetes Mellitus, Type 2, Epinephrine, Female, Glucagon, Humans, Hydrocortisone, Hypoglycemia, Insulin, Male, Psychomotor Performance, Growth Hormone, Glucose Clamp Technique
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