Summary
To examine the long-term effects of recurrent severe hypoglycaemia and other biomedical complications on mental efficiency, a battery of cognitive tests was administered to 142 Type 1 (insulin-dependent) diabetic adult patients (age 33.5±5.6 years; mean ±SD) and 100 demographically similar non-diabetic control subjects. All diabetic subjects had been diagnosed before the age of 17 years. Diabetic subjects with one or more complications (distal symmetrical polyneuropathy; advanced background or proliferative retinopathy; overt nephropathy; one or more episodes of severe hypoglycaemia) performed significantly (p<0.001) more poorly than non-diabetic control subjects on tests requiring sustained attention, rapid analysis of visuospatial detail, and hand eye co-ordination. Regression analyses indicated that the best biomedical predictor of cognitive test performance was a diagnosis of polyneuropathy. Although severe recurrent hypoglycaemia was not associated with performance on any test, the neuropathy × recurrent hypoglycaemia interaction term was significant. These results suggest that in adults with Type 1 diabetes of long duration, recurrent hypoglycaemia does not appear to influence cognitive performance directly, but may interact with neuropathy to exaggerate or otherwise magnify the extent of neurobehavioural dysfunction.
Article PDF
Similar content being viewed by others
References
Holmes CS, Hayford JT, Gonzales JL, Weydert JA (1983) A survey of cognitive functioning at different glucose levels in diabetic persons. Diabetes Care 6: 180–185
Herold KC, Polonsky KS, Cohen RM, Levy J, Douglas F (1985) Variable deterioration in cortical function during insulin-induced hypoglycemia. Diabetes 34: 677–685
Pramming S, Thorsteinsson B, Theilgaard A, Pinner EM, Binder C (1986) Cognitive function during hypoglycaemia in type I diabetes mellitus. Br Med J 292: 647–650
Hoffman RG, Speelman DJ, Hinnen DA, Conley KL, Guthrie RA, Knapp RK (1989) Changes in cortical functioning with acute hypoglycemia and hyperglycemia in type I diabetes. Diabetes Care 3: 193–197
Widom B, Simonson DC (1990) Glycemic control and neuropsychologic function during hypoglycemia in patients with insulin-dependent diabetes mellitus. Ann Intern Med 112: 904–912
Stevens AB, McKane WR, Bell PM, Bell P, King DJ, Hayes JR (1989) Psychomotor performance and counterregulatory responses during mild hypoglycemia in healthy volunteers. Diabetes Care 12: 12–17
Mitrakou A, Ryan C, Veneman T et al. (1991) Hierarchy of glycemia thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. Amer J Physiol 260: E67-E74
Kerr D, Macdonald IA, Tattersall RB (1989) Adaptation to mild hypoglycaemia in normal subjects despite sustained increases in counter-regulatory hormones. Diabetologia 32: 249–254
Bachelard H (1981) Cerebral metabolism and hypoglycaemia. In: Marks V, Rose FC (eds) Hypoglycaemia, 2nd edn. Blackwell Scientific Publications, Oxford, London, pp 51–68
Siesjo BK, Bengtsson F (1989) Calcium fluxes, calcium antagonists, and calcium related pathology in brain ischemia, hypoglycemia and spreading depression: a unifying hypothesis. J Cereb Blood Flow Metab 9: 127–140
Auer RN, Wieloch T, Olsson Y, Siesjo BK (1984) The distribution of hypoglycemia brain damage. Acta Neuropathol 64: 177–191
Wredling R, Levander S, Adamson U, Lins PE (1990) Permanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man. Diabetologia 33: 152–157
Langan SJ, Deary IJ, Hepburn DA, Frier BM (1991) Cumulative cognitive impairment following recurrent severe hypoglycaemia in adult patients with insulin-treated diabetes mellitus. Diabetologia 34: 337–344
Reichard P, Britz A, Rosenqvist U (1991) Intensified conventional insulin treatment and neuropsychological impairment. Br Med J 303: 1439–1442
Deary IJ, Frier BM (1992) Intensified conventional insulin treatment and neuropsychological impairment. Br Med J 304: 447 (Letter)
Reichard P (1992) Author's reply. Br Med J 304: 447 (Letter)
Chase HP, Jackson WE, Hoops SL et al. (1989) Glucose control and the renal and retinal complications of insulin-dependent diabetes. JAMA 261: 1155–1160
Orchard TJ, Dorman JS, Maser RE et al. (1990) Prevalence of complications in IDDM by sex and duration: Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes 39: 1116–1124
DCCT Research Group (1988) Factors in development of diabetic neuropathy: baseline analysis of neuropathy in feasibility phase of Diabetes Control and Complications Trial (DCCT). Diabetes 37: 476–481
Early Treatment of Diabetic Retinopathy Study Coordinating Center (1989) Manual of Operations. University of Maryland, Baltimore
Ryan C, Vega A, Drash A (1985) Cognitive deficits in adolescents who developed diabetes early in life. Pediatr 75: 921–927
Ack M, Miller I, Weil W (1961) Intelligence of children with diabetes mellitus. Pediatr 28: 764–770
Wechsler D (1981) Manual for Wechsler adult intelligence scale-revised. Psychological Corp., New York
Lewis R, Rennick P (1979) Manual for the repeatable cognitiveperceptual-motor battery. Axon, Grosse Pointe Park, Michigan
Ryan C, Morrow L, Bromet E, Parkinson D (1987) Assessment of neuropsychological dysfunction in the workplace: normative data from the Pittsburgh occupational exposures test battery. J Clin Exper Neuropsychol 9: 665–679
Boll T (1981) The Halstead-Reitan neuropsychological battery. In: Filskov S, Boll T (eds) Handbook of clinical neuropsychology. Wiley, New York, pp 577–607
Rourke B, Yanni D, MadDonald G, Young G (1973) Neuropsychological significance of lateralized deficits on the grooved peg board test for older children with learning disabilities. J Consult Clin Psychol 41: 128–134
Wechsler D (1945) A standardized memory scale for clinical use. J Psychol 19: 87–95
SPSS Inc (1988) SPSS/PC + 3.0 for the IBM PC. SPSS, Chicago
Ryan CM, Williams TM, Orchard TJ, Finegold DN (1992) Psychomotor slowing is associated with distal symmetrical polyneuropathy in adults with diabetes mellitus. Diabetes 41: 107–113
Dejgaard A, Gade A, Larsson H. Balle V, Parving A, Parving H (1991) Evidence for diabetic encephalopathy. Diabetic Med 8: 162–167
Tabachnick BG, Fidell LS (1989) Using multivariate statistics 2 nd edn. Harper Collins Publishers, New York
Baron RM, Kenny DA (1986) The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51: 1173–1182
Ryan C (1988) Neurobehavioral complications of type 1 diabetes: examination of possible risk factors. Diabetes Care 11: 86–93
Meuter F, Thomas W, Gruneklee D, Gries F, Lohmann R (1980) Psychometric evaluation of performance in diabetes mellitus. Horm Metab Res 9 [Suppl]: 9–17
Franceschi M, Cecchetto R, Minicucci F, Smizne S, Baio G, Canal N (1984) Cognitive processes in insulin-dependent diabetes. Diabetes Care 7: 228–231
Skenazy J, Bigler E (1984) Neuropsychological findings in diabetes mellitus. J Clin Psychol 40: 246–258
Bale R (1973) Brain damage in diabetes mellitus. Br J Psych 122: 337–341
Rennick P, Wilder R, Sargent J, Ashley B (1968) Retinopathy as an indicator of cognitive-perceptual-motor impairment in diabetic adults [Summary]. Proceedings of the 76 th Annual Convention of the American Psychological Association, pp 473–474
Draelos M, Weinger K, Fritz S, Jacobson A (1992) Cognitive function and long-term glycemic control. Diabetes [Suppl 1] 42: 13A (Abstract)
Wallis WE, Donaldson I, Scott RS, Wilson J (1985) Hypoglycemia masquerading as cerebrovascular disease (hypoglycemic hemiplegia). Ann Neurol 18: 510–512
Chalmers J, Risk MTA, Kean DM et al. (1991) Severe amnesia after hypoglycemia. Diabetes Care 14: 922–925
Patrick AW, Campbell IW (1990) Fatal hypoglycaemia in insulin-treated diabetes mellitus: clinical features and neuropathological changes. Diabetic Med 7: 349–354
Kalimo H, Olsson Y (1980) Effects of severe hypoglycemia on the human brain. Acta Neurol Scandinav. 62: 345–356
Auer RN (1986) Progress review: hypoglycemic brain damage. Stroke 17: 699–708
Myers RE, Kahn KJ (1971) Insulin-induced hypoglycemia in the non-human primate. II. Long-term neuropathological consequences. In: Brierley JB, Meldrum BS (eds) Brain hypoxia. Spastics International Medical Publications, London, pp 195–206
Perlmuter LC, Hakami M, Hodgson-Harrington C et al. (1984) Decreased cognitive function in aging non-insulin-dependent diabetic patients. Am J Med 77: 1043–1048
Mooradian A, Perryman K, Fitten J et al. (1988) Cortical function in elderly non-insulin-dependent diabetic patients. Arch Int Med 148: 2369–2372
Reaven G, Thompson L, Nahum D, Haskins E (1990) Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care 13: 16–21
U'Ren R, Riddle M, Lezak M, Bennington-Davis M (1990) The mental efficiency of the elderly person with type II diabetes mellitus. J Am Geriatric Soc 38: 505–510
Lawson J, Williams Erdahl D, Monga T et al. (1984) Neuropsychological function in diabetic patients with neuropathy. Br J Psych 145: 263–268
Harkins SW, Gardner DF, Anderson RA (1985) Auditory and somatosensory far-field evoked potentials in diabetes mellitus. Int J Neurosci 28: 41–47
Donald MW, Bird CE, Lawson JS, Letemendia FJJ (1981) Delayed auditory brainstem responses in diabetes mellitus. J Neur Neurosurg Psych 44: 641–644
Martini A, Comacchio F, Magnavita V (1991) Auditory brainstem and middle latency evoked responses in the clinical evaluation of diabetes. Diabetic Med 8 [Suppl]: S74-S77
Khardori R, Soler NG, Good DC, DevlescHoward AM, Broughton D, Walbert J (1986) Brainstem auditory and visual evoked potentials in type 1 (insulin-dependent) diabetic patients. Diabetologia 29: 362–365
Frier BM, Hilsted J (1985) Does hypoglycaemia aggravate the complications of diabetes? Lancet II: 1175–1177
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ryan, C.M., Williams, T.M., Finegold, D.N. et al. Cognitive dysfunction in adults with Type 1 (insulin-dependent) diabetes mellitus of long duration: effects of recurrent hypoglycaemia and other chronic complications. Diabetologia 36, 329–334 (1993). https://doi.org/10.1007/BF00400236
Issue Date:
DOI: https://doi.org/10.1007/BF00400236