Effect of Antecedent Hypoglycemia on Cognitive Function and on Glycemie Thresholds for Counterregulatory Hormone Secretion in Healthy Humans

Mellman, Michael; Davis, Maris R.; Brisman, M.; Shamoon, Harry

doi:10.2337/diacare.17.3.183

Cited by 42 publications

(25 citation statements)

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“…The finding of relatively preserved cognitive function after antecedent hypoglycemia agrees with previous data (14,15,25,26,36). On the other hand, several other studies (6,7,23) failed to reveal similar effects of recurrent hypoglycemia.…”

Section: Fruehwald-schultes and Associatessupporting

confidence: 92%

“…The effect of antecedent hypoglycemia on hypoglycemic cognitive dysfunction has been discussed controversially thus far (21,22). Several studies (6,7,14,23) failed to detect any significant effects, whereas others (15,(24)(25)(26) indicated a preserving influence of antecedent hypoglycemia on cognitive function. The inconsistency appears to be related to methodical differences pertaining to the heterogeneity of the subjects studied, the small size of subject samples, and the cognitive function tests used.…”

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confidence: 99%

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Adaptation of cognitive function to hypoglycemia in healthy men.

et al. 2000

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Abbreviations: AEBP, auditory-evoked brain potential; ANCOVA, analysis of covariance; Cz, central electrode location; EEG, electroencephalogram; EOG, electrooculogram; Fz, frontal electrode location; prior-hypo group, subjects who received a 2.5-h antecedent hypoglycemic clamp on the preceding day; Pz, parietal electrode location.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Adaptation of Cognitive Function to Hypoglycemia in Healthy Men O R I G I N A L A R T I C L EOBJECTIVE -Antecedent hypoglycemia reduces hypoglycemic counterregulation and symptoms, thereby provoking the hypoglycemia unawareness syndrome. The effects of antecedent hypoglycemia on hypoglycemia-induced cognitive dysfunction are less well established.RESEARCH DESIGN AND METHODS -To determine whether antecedent hypoglycemia also reduces hypoglycemic cognitive dysfunction, we performed stepwise hypoglycemic clamp experiments (4.1, 3.6, 3.1, and 2.6 mmol/l) during a 6-h period in 30 young healthy men. A total of 15 subjects additionally received a 2.5-h antecedent hypoglycemic clamp (3.1 mmol/l) on the preceding day (prior-hypo group), whereas the other 15 subjects did not (control group). Cognitive function was assessed by auditory-evoked brain potentials (AEBPs) and reaction time during a vigilance task and short-term memory recall. Tests were performed during the stepwise hypoglycemic clamp at baseline and at each hypoglycemic plateau.RESULTS -In both groups, performance on all measures of cognitive function deteriorated during stepwise hypoglycemia (all P Ͻ 0.01). However, after antecedent hypoglycemia, the hypoglycemia-induced decrease in the amplitude of the P3 of the AEBP was distinctly reduced compared with the control condition (P Ͻ 0.05). Also, short-term memory performance was less impaired in the prior-hypo group than in the control group (P Ͻ 0.005), and a minor hypoglycemic impairment of reaction time (P Ͻ 0.05) was evident in the prior-hypo group.CONCLUSIONS -Data provide evidence that a single episode of mild antecedent hypoglycemia (3.1 mmol/l) attenuates several aspects of cognitive dysfunction during subsequent hypoglycemia 18-24 h later. Diabetes C l i n i c a l C a r e / E d u c a t i o n / N u t r i t i o n 1060DIABETES CARE, VOLUME 23, NUMBER 8, AUGUST 2000Hypoglycemia and cognitive function formed in 30 subjects randomly allocated to 2 groups. One group additionally underwent an antecedent hypoglycemic clamp that lasted 2.5 h on the day preceding the stepwise hypoglycemia (priorhypo group), whereas the other 15 subjects did not undergo the clamp study (control group). A moderate antecedent hypoglycemic level of ϳ3.1 mmol/l was chosen because, under this condition, antecedent hypoglycemia per se is not expected to induce acute cognitive disturbances that may interfere with the effects of subsequent hypoglycemia (27-30).On the day of the antecedent hypoglycemic clamp study, the subjects in the prior-hypo group reported to the medical researc...

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Section: Fruehwald-schultes and Associatessupporting

confidence: 92%

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confidence: 99%

Adaptation of cognitive function to hypoglycemia in healthy men.

et al. 2000

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“…Cognitive dysfunction begins at lower blood glucose levels in people with type 1 diabetes and IHA compared with those with NHA (13), and antecedent hypoglycemia in individuals with type 1 diabetes and NHA can shift the thresholds for cognitive dysfunction to lower blood glucose levels (9,10,22,23). Glucose clamp studies in nondiabetic individuals have shown that 90 -150 min of hypoglycemia the day before cognitive testing attenuates the deterioration in short-term memory, reaction time, and auditory-evoked brain potentials (11,24,25), and avoidance of hypoglycemia can restore the glucose thresholds for cognitive dysfunction to higher levels (7,8,12). A previous, smaller study from our center compared the effects of hypoglycemia on cognitive function in 20 people with type 1 diabetes with either IHA or NHA and reported a trend toward poorer performance during hypoglycemia in IHA subjects (14).…”

Section: Discussionmentioning

confidence: 99%

Delayed Recovery of Cognitive Function Following Hypoglycemia in Adults With Type 1 Diabetes

et al. 2008

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OBJECTIVE-Recovery times of cognitive functions were examined after exposure to hypoglycemia in people with diabetes with and without impaired hypoglycemia awareness.RESEARCH DESIGN AND METHODS-A total of 36 subjects with type 1 diabetes were studied (20 with normal hypoglycemia awareness [NHA] and 16 with impaired hypoglycemia awareness [IHA]). A hyperinsulinemic glucose clamp was used to lower blood glucose to 2.5 mmol/l (45 mg/dl) (hypoglycemia) for 1 h or to maintain blood glucose at 4.5 mmol/l (81 mg/dl) (euglycemia) on separate occasions. Cognitive tests were applied during each experimental condition and were repeated at 10-to 15-min intervals for 90 min after euglycemia had been restored.RESULTS-In the NHA group, performance was impaired on all cognitive tasks during hypoglycemia and remained impaired for up to 75 min on the choice reaction time (CRT) task (P ϭ 0.03, 2 ϭ 0.237). In the IHA group, performance did not deteriorate significantly during hypoglycemia. When all subjects were analyzed within the same general linear model, performance was impaired during hypoglycemia on all tasks. Significant impairment during recovery persisted for up to 40 min on the CRT task (P ϭ 0.04, 2 ϭ 0.125) with a significant glycemia-awareness interaction for CRT after one hour of hypoglycemia (P ϭ 0.045, 2 ϭ 0.124). Performance on the trail-making B task was impaired for up to 10 min after euglycemia was restored (P ϭ 0.024, 2 ϭ 0.158). T he recovery of cognitive function following hypoglycemia has not received rigorous evaluation. Previous studies examined nondiabetic volunteers (1-3) in small numbers (3), did not include a euglycemia control arm (1,4), measured neurophysiological parameters rather than cognitive function (1,2,5,6), or restricted cognitive testing to one or two time points (3-5). The interval between restoration of euglycemia and cognitive testing was usually ill defined (2,4 -6). Controversy exists as to whether impaired awareness of hypoglycemia is associated with relative preservation (7-13) or exacerbation of the cognitive impairment induced by hypoglycemia (14 -16). The present study examined the time taken for recovery of cognitive function in adults with type 1 diabetes and assessed the effect of their state of awareness on the response to, and recovery from, hypoglycemia. CONCLUSIONS-Following RESEARCH DESIGN AND METHODSThe local medical research ethics committee approved the protocol, and subjects gave informed consent for participation.Inclusion criteria were a diagnosis of type 1 diabetes and age 18 -45 years. Exclusion criteria included pregnancy or any significant concurrent medical condition, history of head injury, epilepsy, or history of hypoglycemia-induced seizure.A total of 36 subjects with type 1 diabetes were recruited, 20 with normal hypoglycemia awareness (NHA) and 16 with impaired hypoglycemia awareness (IHA) confirmed by documenting their hypoglycemia history and using a validated hypoglycemia awareness scale (17). Microvascular complications were defined as any clinical diag...

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“…For example, in the insulinoma patients studied by Mitrakou et al [15], and in intensively insulin-treated IDDM patients [5,11,13,16] antecedent hypoglycaemia was recurrent. In contrast, a single episode of hypoglycaemia lasting 56 h, was induced in non-diabetic subjects in the study by Boyle et al [9], whereas other studies induced only one episode of hypoglycaemia for only 2 h [8,17]. Despite these differences, all these studies do show at least some degree of downward shifting in glycaemic thresholds for cognitive dysfunction.…”

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confidence: 98%