Hypoglycemia-induced cognitive dysfunction in diabetes mellitus: Effect of hypoglycemia unawareness
Abstract
Hypoglycemia results in cognitive dysfunction. The aim of this study was to assess and compare the degree of cognitive dysfunction experienced by insulin-dependent diabetic patients (IDDM) with hypoglycemia unawareness with patients with normal awareness of hypoglycemia. Cognitive function was examined in 10 patients who had normal awareness of the onset of hypoglycemia and 10 patients who had a history of impaired awareness of hypoglycemia. A hyperinsulinemic glucose clamp was used to manipulate blood glucose concentrations. Cognitive function was assessed using Rapid Visual Information Processing (RVIP), Trial Making B (TMB), Paced Auditory Serial Addition Test (PASAT) and Digit Symbol Substitution Test (DSST). Multivariate analysis of variance demonstrated a significant effect of hypoglycemia on cognitive function (p < 0.01). A trend was observed towards an overall effect of awareness on performance (p = 0.08). There were trends in the effects of awareness on RVIP correct responses across time (p = 0.07) and the interaction of awareness by study by TMB (p = 0.08). During hypoglycemia subjects with impaired awareness were less cautious in their responses (RVIP misses p = 0.03) and on recovery from hypoglycemia, their cognitive function remained abnormal (TMB p = 0.04, RVIP correct responses p = 0.02, RVIP misses p = 0.04). Thus, IDDM patients with hypoglycemia unawareness exhibited more profound cognitive dysfunction during acute hypoglycemia which persisted for longer following blood glucose recovery.
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In patients with T1D, cognitive function and intellectual activity are likely to be impaired during acute hypoglycemia.
“In patients with T1D, cognitive function and intellectual activity are likely to be impaired during acute hypoglycemia.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [41]
This impairment persists for a longer period after a hypoglycemic episode.
“Furthermore, this impairment persists for a longer period after a hypoglycemic episode [ 41 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [41]
Cites
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425 · see citing works
Manual for the Wechsler Adult Intelligence Scale.
Wechsler, D. (1955) · Psychological Corp. eBooks · Cited by 4,941 · see citing works
Clinical neuropsychology: Current status and applications
(1975) · Behavior Therapy · doi:10.1016/s0005-7894(75)80088-8 · Cited by 1,556 · see citing works
The two‐period cross‐over clinical trial.
Hills, M., & Armitage, P. (1979) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1979.tb05903.x · Cited by 1,403 · see citing works
Gold, A. E., Macleod, K. M., & Frier, B. M. (1994) · Diabetes Care · doi:10.2337/diacare.17.7.697 · Cited by 810 · see citing works
Self-citationEffects of scopolamine and nicotine on human rapid information processing performance
Wesnes, K. A., & Warburton, D. M. (1984) · Psychopharmacology · doi:10.1007/bf00427761 · Cited by 354 · see citing works
Symptomatic Hypoglycaemia in 411 Type 1 Diabetic Patients
Pramming, S., Thorsteinsson, B., Bendtson, I., & Binder, C. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01575.x · Cited by 336 · see citing works
A Survey of Cognitive Functioning at Different Glucose Levels in Diabetic Persons
Holmes, C. S., Hayford, J. T., González, J. L., & Weydert, J. A. (1983) · Diabetes Care · doi:10.2337/diacare.6.2.180 · Cited by 216 · see citing works
Hepburn, D. A., Patrick, A. W., Eadington, D. W., Ewing, D. J., & Frier, B. M. (1990) · Diabetic Medicine · doi:10.1111/j.1464-5491.1990.tb01475.x · Cited by 179 · see citing works
Self-citationPermanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man
Wredling, R., Levander, S. E., Adamson, U., & Lins, P. E. (1990) · Diabetologia · doi:10.1007/bf00404042 · Cited by 159 · see citing works
Evidence for Diabetic Encephalopathy
Dejgaard, A., Gade, A., Larsson, H. B. W., Balle, V. H., Parving, A., & Parving, H. ‐. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01564.x · Cited by 157 · see citing works
Blood glucose and human memory
Benton, D., & Owens, D. S. (1993) · Psychopharmacology · doi:10.1007/bf02244338 · Cited by 152 · see citing works
Cognitive function during hypoglycaemia in type I diabetes mellitus.
Pramming, S., Thorsteinsson, B., Theilgaard, A., Pinner, E. M., & Binder, C. (1986) · BMJ · doi:10.1136/bmj.292.6521.647 · Cited by 136 · see citing works
Ryan, C. M., Atchison, J., Puczynski, S., et al. (1990) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)82440-0 · Cited by 132 · see citing works
Widom, B., & Simonson, D. C. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-112-12-904 · Cited by 131 · see citing works
Severe Hypoglycemia and Intelligence in Adult Patients With Insulin-Treated Diabetes
Deary, I. J., Crawford, J. R., Hepburn, D. A., Langan, S. J., Blackmore, L., & Frier, B. M. (1993) · Diabetes · doi:10.2337/diab.42.2.341 · Cited by 128 · see citing works
Self-citation(1993) · Edward Arnold eBooks · Cited by 113 · see citing works
INFLUENCE OF SYMPATHETIC NERVOUS SYSTEM ON HYPOGLYCAEMIC WARNING SYMPTOMS
Heller, S. R., Herbert, M., Macdonald, I. A., & Tattersall, R. B. (1987) · The Lancet · doi:10.1016/s0140-6736(87)92382-8 · Cited by 109 · see citing works
The Impact of Raising Blood Glucose on Reaction Times
Owens, D. S., & Benton, D. (2008) · Neuropsychobiology · doi:10.1159/000119146 · Cited by 108 · see citing works
Ryan, C. M., Williams, T. M., Orchard, T. J., & Finegold, D. N. (1992) · Diabetes · doi:10.2337/diab.41.1.107 · Cited by 107 · see citing works
Frier, B. M. (1986) · Diabetic Medicine · doi:10.1111/j.1464-5491.1986.tb00807.x · Cited by 103 · see citing works
Self-citationPozzessere, G., Rizzo, P. A., Valle, E., et al. (1988) · Diabetes Care · doi:10.2337/diacare.11.6.473 · Cited by 86 · see citing works
Pozzessere, G., Valle, E., de Crignis, S., et al. (1991) · Diabetes · doi:10.2337/diab.40.8.952 · Cited by 84 · see citing works
Variable Deterioration in Cortical Function During Insulin-induced Hypoglycemia
Herold, K. C., Polonsky, K. S., Cohen, R. M., Levy, J., & Douglas, F. L. (1985) · Diabetes · doi:10.2337/diab.34.7.677 · Cited by 78 · see citing works
Cognitive function in diabetes mellitus
Richardson, J. T. E. (1990) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80060-0 · Cited by 75 · see citing works
Brainstem auditory and visual evoked potentials in Type 1 (insulin-dependent) diabetic patients
Khardori, R. K., Soler, N. G., Good, D. C., et al. (1986) · Diabetologia · doi:10.1007/bf00903345 · Cited by 71 · see citing works
Hepburn, D. A., Patrick, A. W., Brash, H. M., Thomson, I., & Frier, B. M. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01533.x · Cited by 68 · see citing works
Self-citationHypoglycemic Thresholds for Cognitive Dysfunction in IDDM
Blackman, J. D., Towle, V. L., Sturis, J., Flewis, G., Spire, J., & Polonsky, K. S. (1992) · Diabetes · doi:10.2337/diab.41.3.392 · Cited by 63 · see citing works
Changes in Cortical Functioning With Acute Hypoglycemia and Hyperglycemia in Type I Diabetes
Hoffman, R. G., Speelman, D. J., Hinnen, D. A., et al. (1989) · Diabetes Care · doi:10.2337/diacare.12.3.193 · Cited by 61 · see citing works
Stevens, A. B., McKane, W. R., Bell, P. M., Bell, P., King, D. J., & Hayes, J. R. (1989) · Diabetes Care · doi:10.2337/diacare.12.1.12 · Cited by 53 · see citing works
Which abilities does the PASAT test?
Deary, I. J., Langan, S. J., Hepburn, D. A., & Frier, B. M. (1991) · Personality and Individual Differences · doi:10.1016/0191-8869(91)90027-9 · Cited by 50 · see citing works
Self-citationMaran, A., Lomas, J., Archibald, H. R., Macdonald, I. A., Gale, E. A. M., & Amiel, S. A. (1993) · BMJ · doi:10.1136/bmj.306.6871.167 · Cited by 45 · see citing works
Recurrent severe hypoglycemia, intelligence, and speed of information processing
Deary, I. J., Langan, S. J., Graham, K. S., Hepburn, D. A., & Frier, B. M. (1992) · Intelligence · doi:10.1016/0160-2896(92)90014-i · Cited by 43 · see citing works
Self-citationWirsén, A., Tallroth, G., Lindgren, M. P., & Agardh, C. (1992) · Diabetic Medicine · doi:10.1111/j.1464-5491.1992.tb01753.x · Cited by 36 · see citing works
Patients with Type 1 Diabetes Adapt Acutely to Sustained Mild Hypoglycaemia
Kerr, D. E., Macdonald, I. A., & Tattersall, R. B. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01557.x · Cited by 34 · see citing works
Disruptive Effects of Acute Hypoglycemia on Speed of Cognitive and Motor Performance
Cox, D. J., Gonder-Frederick, L. A., Schroeder, D. B., Cryer, P. E., & Clarke, W. L. (1993) · Diabetes Care · doi:10.2337/diacare.16.10.1391 · Cited by 33 · see citing works
Kerr, D. E., Macdonald, I. A., & Tattersall, R. B. (1989) · Diabetologia · doi:10.1007/bf00285293 · Cited by 30 · see citing works
Influence of plasma glucose rate of decrease on hierarchy of responses to hypoglycemia
Mitrakou, A., Mokáň, M., Ryan, C. M., Veneman, T. F., Cryer, P., & Gerich, J. E. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.76.2.8432790 · Cited by 23 · see citing works
(1992) · Diabetologia · doi:10.1007/bf00585995 · Cited by 3 · see citing works
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Brands, A. M. A., Biessels, G. J., de Haan, E. H. F., Kappelle, L. J., & Kessels, R. P. C. (2005) · Diabetes Care · doi:10.2337/diacare.28.3.726 · Cited by 738 · see citing works
Mechanisms of hypoglycemia unawareness and implications in diabetic patients
Martín-Timón, I. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i7.912 · Cited by 204 · see citing works
Digital neuropsychology: challenges and opportunities at the intersection of science and software
Germine, L., Reinecke, K., & Chaytor, N. S. (2019) · The Clinical Neuropsychologist · doi:10.1080/13854046.2018.1535662 · Cited by 171 · see citing works
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Christie, S. T., & Schrater, P. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00289 · Cited by 99 · see citing works
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Self-citation
- Authors
- Gold, A. E., MacLeod, K. M., Deary, I. J., & Frier, B. M.
- Affiliations
- Edinburgh Royal Infirmary (GB)
- University of Edinburgh (GB)
- Corresponding author
- Gold, Ann E.
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 1995-09
- Volume
- 58
- Issue
- 3
- Pages
- 501-511
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W1992686377
- Cited by
- 81
- References
- 39
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Dietetic Association
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Neurological and metabolic disorders
- Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
- Keywords
- hypoglycemia, hypoglycemia unawareness, cognitive impairment, type 1 diabetes, hyperinsulinemic-euglycemic clamp, attention, executive function, visuospatial processing
- MeSH terms
- Adult, Arousal, Attention, Awareness, Blood Pressure, Cerebral Cortex, Cognition Disorders, Diabetes Mellitus, Type 1, Female, Heart Rate, Humans, Hypoglycemia, Male, Neuropsychological Tests
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