Shift of glycaemic thresholds for cognitive function in hypoglycaemia unawareness in humans

Fanelli, Carmine G.; Pampanelli, S.; Porcellati, Francesca; Bolli, Geremia B.

doi:10.1007/s001250050974

Cited by 33 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The degree of cognitive adaptation acquired by those with IHA is insufficient to compensate completely for the loss of physical symptoms. 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).…”

Section: Discussionmentioning

confidence: 99%

“…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)(8)(9)(10)(11)(12)(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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2008

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Moreover, recurrent hypoglycemia also impairs the body's defence mechanisms against hypoglycemia. Many patients with diabetes display a progressive decay in the counterregulatory response over time, resulting in reduction of hypoglycemia awareness [2], where the glycemia threshold for counter-regulation is shifted to lower plasma glucose levels and may be detected only upon severe neuroglycopenia [3].…”

Section: Introductionmentioning

confidence: 99%

“…Much less is known about the mechanisms responsible for hypoglycemia unawareness, where a drop in glycemia is only detected when neuroglycopenia occurs [3]. It has been proposed that recurrent hypoglycemia leads to increased fuel availability to the brain, either glucose [5][6][7] or monocarboxylates [8] that are readily available from circulation.…”

Section: Introductionmentioning

confidence: 99%

Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery

2017

View full text Add to dashboard Cite

show abstract

“…Such episodes can last 1-12 h (2-6) and, except for disturbed awakening behavior (7,8), frequently appear to be asymptomatic (9,10). However, hypoglycemic episodes during nocturnal sleep have been shown to diminish counterregulatory and symptomatic responses to subsequent hypoglycemia (11,12). Whereas the deteriorating impact on cognitive functions of hypoglycemia in the waking state is well known (13), the influences of nocturnal hypoglycemic episodes on cognitive functions and mood on the following day have been rarely investigated.…”

mentioning

confidence: 99%

Hypoglycemia During Sleep Impairs Consolidation of Declarative Memory in Type 1 Diabetic and Healthy Humans

et al. 2007

View full text Add to dashboard Cite

OBJECTIVE -Early nocturnal sleep enhances the consolidation of declarative memories acquired during prior wakefulness. Patients with type 1 diabetes frequently experience hypoglycemic episodes during sleep. We investigated whether short-lasting hypoglycemia during early nocturnal sleep affects the sleep-associated consolidation of declarative memories.RESEARCH DESIGN AND METHODS -Sixteen type 1 diabetic patients and 16 healthy subjects matched for age and BMI were tested. On one condition, a linear fall of plasma glucose to 2.2 mmol/l was induced within 60 min by infusing insulin during early sleep. On the control condition, euglycemia (Ͼ3.86 mmol/l) was maintained throughout the night. In the morning, subjects recalled word pairs learned in the preceding evening. To assess mood and attention, a symptom questionnaire, an adjective check list, and the Stroop test were applied. Also, auditory event-related brain potentials were recorded.RESULTS -After euglycemia, subjects recalled 1.5 Ϯ 0.5 more word pairs than after hypoglycemia (P Ͻ 0.01), remembering 2.0 Ϯ 0.6 more word pairs than at immediate recall before sleep (P ϭ 0.002). Across the hypoglycemic night, no such gain occurred (ϩ0.5 Ϯ 0.6 words; P ϭ 0.41). Hypoglycemia during sleep also impaired mood (P Ͻ 0.05) but did not affect attention. Effects compared well between type 1 diabetic patients and healthy control subjects.CONCLUSIONS -Our findings indicate specific sensitivity of declarative memory consolidation during sleep to rather short episodes of mild hypoglycemia. This effect may disable memory processing in type 1 diabetic patients prone to nocturnal hypoglycemic episodes and underlines the importance of considering sleep as a critical period in the treatment of these patients. Diabetes Care 30:2040-2045, 2007H ypoglycemic episodes during sleep constitute a particular problem in patients with type 1 diabetes, with incidence rates of up to 56% of nights (1-4). Such episodes can last 1-12 h (2-6) and, except for disturbed awakening behavior (7,8), frequently appear to be asymptomatic (9,10). However, hypoglycemic episodes during nocturnal sleep have been shown to diminish counterregulatory and symptomatic responses to subsequent hypoglycemia (11,12). Whereas the deteriorating impact on cognitive functions of hypoglycemia in the waking state is well known (13), the influences of nocturnal hypoglycemic episodes on cognitive functions and mood on the following day have been rarely investigated. Two studies (14,15) failed to reveal adverse effects of nocturnal hypoglycemia on cognitive functions assessed in the next morning, whereas mood was impaired (15). However, the neurocognitive tests used in these studies mainly assessed aspects of acute stimulus processing, i.e., functions that at the time of testing may have recovered from effects of nocturnal hypoglycemia. No attempt has been made as yet to assess the immediate impact of hypoglycemia on ongoing stimulus processing during sleep.Increasing evidence suggests that sleep benefits memory consolidation (1...

show abstract

Shift of glycaemic thresholds for cognitive function in hypoglycaemia unawareness in humans

Cited by 33 publications

References 26 publications

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

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

Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery

Hypoglycemia During Sleep Impairs Consolidation of Declarative Memory in Type 1 Diabetic and Healthy Humans

Contact Info

Product

Resources

About