• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Aug 1988; 82(2): 436–444.
PMCID: PMC303532

Modest decrements in plasma glucose concentration cause early impairment in cognitive function and later activation of glucose counterregulation in the absence of hypoglycemic symptoms in normal man.

Abstract

To establish the glycemic threshold for onset of neuroglycopenia (impaired cognitive function, measured by the latency of the P300 wave), activation of hormonal counterregulation and hypoglycemic symptoms, 12 normal subjects were studied either under conditions of insulin-induced, glucose-controlled plasma glucose decrements, or during maintenance of euglycemia. A decrement in plasma glucose concentration from 88 +/- 3 to 80 +/- 1 mg/dl for 150 min did not result in changes in the latency of the P300 wave nor in an activation of counterregulatory hormonal response. In contrast, a greater decrement in plasma glucose concentration from 87 +/- 3 to 72 +/- 1 mg/dl for 120 min caused an increase in the latency of the P300 wave (from 301 +/- 12 to 348 +/- 20 ms, P less than 0.01), a subsequent increase in all counterregulatory hormones but no hypoglycemic symptoms. Finally, when plasma glucose concentration was decreased in a stepwise manner from 88 +/- 2 to 50 +/- 1 mg/dl within 75 min, the increase in the latency of the P300 wave was correlated with the corresponding plasma glucose concentration (r = -0.76, P less than 0.001). The glycemic threshold for hypoglycemic symptoms was 49 +/- 2 mg/dl. Thus, in normal man the glycemic threshold for neuroglycopenia (72 +/- 1 mg/dl) is greater than currently thought; the hormonal counterregulation follows the onset of neuroglycopenia; the hypoglycemic symptoms are a late indicator of advanced neuroglycopenia.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cryer PE, Gerich JE. Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. N Engl J Med. 1985 Jul 25;313(4):232–241. [PubMed]
  • Robinson PJ, Rapoport SI. Glucose transport and metabolism in the brain. Am J Physiol. 1986 Jan;250(1 Pt 2):R127–R136. [PubMed]
  • Holmes CS, Hayford JT, Gonzalez JL, Weydert JA. A survey of cognitive functioning at difference glucose levels in diabetic persons. Diabetes Care. 1983 Mar-Apr;6(2):180–185. [PubMed]
  • Holmes CS, Koepke KM, Thompson RG, Gyves PW, Weydert JA. Verbal fluency and naming performance in type I diabetes at different blood glucose concentrations. Diabetes Care. 1984 Sep-Oct;7(5):454–459. [PubMed]
  • Pramming S, Thorsteinsson B, Theilgaard A, Pinner EM, Binder C. Cognitive function during hypoglycaemia in type I diabetes mellitus. Br Med J (Clin Res Ed) 1986 Mar 8;292(6521):647–650. [PMC free article] [PubMed]
  • Herold KC, Polonsky KS, Cohen RM, Levy J, Douglas F. Variable deterioration in cortical function during insulin-induced hypoglycemia. Diabetes. 1985 Jul;34(7):677–685. [PubMed]
  • Pramming S, Thorsteinsson B, Stigsby B, Binder C. Glycaemic threshold for changes in electroencephalograms during hypoglycaemia in patients with insulin dependent diabetes. Br Med J (Clin Res Ed) 1988 Mar 5;296(6623):665–667. [PMC free article] [PubMed]
  • McGuire EA, Helderman JH, Tobin JD, Andres R, Berman M. Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol. 1976 Oct;41(4):565–573. [PubMed]
  • DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. [PubMed]
  • Bolli G, De Feo P, Perriello G, De Cosmo S, Compagnucci P, Santeusanio F, Brunetti P, Unger RH. Mechanisms of glucagon secretion during insulin-induced hypoglycemia in man. Role of the beta cell and arterial hyperinsulinemia. J Clin Invest. 1984 Apr;73(4):917–922. [PMC free article] [PubMed]
  • Herbert V, Lau KS, Gottlieb CW, Bleicher SJ. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. [PubMed]
  • Da Prada M, Zürcher Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 1976 Oct 15;19(8):1161–1174. [PubMed]
  • MATTINGLY D. A simple fluorimetric method for the estimation of free 11-hydroxycorticoids in human plasma. J Clin Pathol. 1962 Jul;15:374–379. [PMC free article] [PubMed]
  • DOLE VP, MEINERTZ H. Microdetermination of long-chain fatty acids in plasma and tissues. J Biol Chem. 1960 Sep;235:2595–2599. [PubMed]
  • Sutton S, Braren M, Zubin J, John ER. Evoked-potential correlates of stimulus uncertainty. Science. 1965 Nov 26;150(3700):1187–1188. [PubMed]
  • Goodin DS, Squires KC, Starr A. Long latency event-related components of the auditory evoked potential in dementia. Brain. 1978 Dec;101(4):635–648. [PubMed]
  • Finley WW, Faux SF, Hutcheson J, Amstutz L. Long-latency event-related potentials in the evaluation of cognitive function in children. Neurology. 1985 Mar;35(3):323–327. [PubMed]
  • Doberne L, Greenfield MS, Schulz B, Reaven GM. Enhanced glucose utilization during prolonged glucose clamp studies. Diabetes. 1981 Oct;30(10):829–835. [PubMed]
  • Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest. 1987 Mar;79(3):777–781. [PMC free article] [PubMed]
  • Hillyard SA, Kutas M. Electrophysiology of cognitive processing. Annu Rev Psychol. 1983;34:33–61. [PubMed]
  • Pritchard WS. Psychophysiology of P300. Psychol Bull. 1981 May;89(3):506–540. [PubMed]
  • Halgren E, Squires NK, Wilson CL, Rohrbaugh JW, Babb TL, Crandall PH. Endogenous potentials generated in the human hippocampal formation and amygdala by infrequent events. Science. 1980 Nov 14;210(4471):803–805. [PubMed]
  • Okada YC, Kaufman L, Williamson SJ. The hippocampal formation as a source of the slow endogenous potentials. Electroencephalogr Clin Neurophysiol. 1983 Apr;55(4):417–426. [PubMed]
  • Adam N, Collins GI. Late components of the visual evoked potential to search in short-term memory. Electroencephalogr Clin Neurophysiol. 1978 Feb;44(2):147–156. [PubMed]
  • Polich J, Howard L, Starr A. P300 latency correlates with digit span. Psychophysiology. 1983 Nov;20(6):665–669. [PubMed]
  • Goodin DS, Squires KC, Henderson BH, Starr A. Age-related variations in evoked potentials to auditory stimuli in normal human subjects. Electroencephalogr Clin Neurophysiol. 1978 Apr;44(4):447–458. [PubMed]
  • Rosenberg C, Nudleman K, Starr A. Cognitive evoked potentials (P300) in early Huntington's disease. Arch Neurol. 1985 Oct;42(10):984–987. [PubMed]
  • Bolli GB, Gottesman IS, Cryer PE, Gerich JE. Glucose counterregulation during prolonged hypoglycemia in normal humans. Am J Physiol. 1984 Aug;247(2 Pt 1):E206–E214. [PubMed]
  • Pardridge WM. Brain metabolism: a perspective from the blood-brain barrier. Physiol Rev. 1983 Oct;63(4):1481–1535. [PubMed]
  • Corrall RJ, Frier BM, Davidson NM, French EB. Hormonal and substrate responses during recovery from hypoglycaemia in man during beta 1-selective and non-selective beta-adrenergic blockade. Eur J Clin Invest. 1981 Aug;11(4):279–283. [PubMed]
  • Gjedde A, Crone C. Blood-brain glucose transfer: repression in chronic hyperglycemia. Science. 1981 Oct 23;214(4519):456–457. [PubMed]
  • McCall AL, Millington WR, Wurtman RJ. Metabolic fuel and amino acid transport into the brain in experimental diabetes mellitus. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5406–5410. [PMC free article] [PubMed]
  • McCall AL, Fixman LB, Fleming N, Tornheim K, Chick W, Ruderman NB. Chronic hypoglycemia increases brain glucose transport. Am J Physiol. 1986 Oct;251(4 Pt 1):E442–E447. [PubMed]
  • Bergenstal RM, Polonsky KS, Pons G, Jaspan JB, Rubenstein AH. Lack of glucagon response to hypoglycemia in type I diabetics after long-term optimal therapy with a continuous subcutaneous insulin infusion pump. Diabetes. 1983 May;32(5):398–402. [PubMed]
  • Arias P, Kerner W, Zier H, Navascués I, Pfeiffer EF. Incidence of hypoglycemic episodes in diabetic patients under continuous subcutaneous insulin infusion and intensified conventional insulin treatment: assessment by means of semiambulatory 24-hour continuous blood glucose monitoring. Diabetes Care. 1985 Mar-Apr;8(2):134–140. [PubMed]
  • Lager I, Attvall S, Blohmé G, Smith U. Altered recognition of hypoglycaemic symptoms in type I diabetes during intensified control with continuous subcutaneous insulin infusion. Diabet Med. 1986 Jul-Aug;3(4):322–325. [PubMed]
  • Simonson DC, Tamborlane WV, DeFronzo RA, Sherwin RS. Intensive insulin therapy reduces counterregulatory hormone responses to hypoglycemia in patients with type I diabetes. Ann Intern Med. 1985 Aug;103(2):184–190. [PubMed]
  • Amiel SA, Tamborlane WV, Simonson DC, Sherwin RS. Defective glucose counterregulation after strict glycemic control of insulin-dependent diabetes mellitus. N Engl J Med. 1987 May 28;316(22):1376–1383. [PubMed]
  • De Feo P, Perriello G, De Cosmo S, Ventura MM, Campbell PJ, Brunetti P, Gerich JE, Bolli GB. Comparison of glucose counterregulation during short-term and prolonged hypoglycemia in normal humans. Diabetes. 1986 May;35(5):563–569. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...