Acute Hypoglycemia Impairs Executive Cognitive Function in Adults With and Without Type 1 Diabetes

Graveling, Alex; Deary, Ian J.; Frier, Brian M.

doi:10.2337/dc13-0194

Cited by 67 publications

(49 citation statements)

References 38 publications

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“…Experimental studies in animals demonstrate that cognitive functions are severely compromised during periods of energy shortage (Valadares et al, ; Plaçais & Preat, ). Similar observations have been made in humans: even short periods of hypoglycaemia adversely affect cognitive function with complex functions such as memory or attention particularly affected (Deary et al, ; Graveling, Deary & Frier, ). Although, no study investigating the association between pregnancy and cognitive functioning has controlled for levels of glucose or other sources of metabolic energy, studies on hypoglycaemic states in diabetic patients and non‐diabetic controls may shed some light on this association.…”

Section: The Cognitive Costs Of Reproduction Hypothesissupporting

confidence: 65%

Cognitive costs of reproduction: life‐history trade‐offs explain cognitive decline during pregnancy in women

2018

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Life-history theory predicts that access to limited resources leads to trade-offs between competing body functions. Women, who face higher costs of reproduction when compared to men, should be especially vulnerable to these trade-offs. We propose the 'cognitive costs of reproduction hypothesis', which states that energy trade-offs imposed by reproduction may lead to a decline in maternal cognitive function during gestation. In particular, we hypothesize that the decline in cognitive function frequently observed during pregnancy is associated with the allocation of resources between the competing energetic requirements of the mother's brain and the developing foetus. Several distinctive anatomical and physiological features including a high metabolic rate of the brain, large infant size, specific anatomical features of the placenta and trophoblast, and the lack of maternal control over glucose flow through the placenta make the occurrence of these trade-offs likely.Herein, we review several lines of evidence for trade-offs between gestation and cognition that are related to: (i) energy metabolism during reproduction; (ii) energy metabolism of the human brain; (iii) links between energy metabolism and cognitive function; and (iv) links between gestation and cognitive function. We also review evidence for the important roles of cortisol, corticotropin-releasing hormone and sex hormones in mediating the effects of gestation on cognition, and we discuss possible neurophysiological mechanisms underlying the observed effects. The evidence supports the view that energy trade-offs between foetal growth and maternal endocrine and brain function lead to changes in maternal cognition, and that this phenomenon is mediated by neuroendocrine mechanisms involving the hypothalamic-pituitary-adrenal axis, brainstem nucleus locus coeruleus and hippocampus.

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Section: The Cognitive Costs Of Reproduction Hypothesissupporting

confidence: 65%

Cognitive costs of reproduction: life‐history trade‐offs explain cognitive decline during pregnancy in women

2018

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“…Choice reaction time is used to examine psychomotor and attentional focus. Acute hypoglycaemia markedly impairs performance in almost all aspects of executive function in adults with type 1 diabetes, with time taken to complete cognitive testing taking considerably longer [42,43]. Zammitt et al have shown that 4CRT is also prolonged during experimental hypoglycaemia in people with type 1 diabetes and intact awareness, but not in those with IAH [44].…”

Section: Discussionmentioning

confidence: 99%

A randomised controlled study of high intensity exercise as a dishabituating stimulus to improve hypoglycaemia awareness in people with type 1 diabetes: a proof-of-concept study

et al. 2020

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Aims/hypothesis Approximately 25% of people with type 1 diabetes have suppressed counterregulatory hormonal and symptomatic responses to insulin-induced hypoglycaemia, which renders them at increased risk of severe, disabling hypoglycaemia. This is called impaired awareness of hypoglycaemia (IAH), the cause of which is unknown. We recently proposed that IAH develops through habituation, a form of adaptive memory to preceding hypoglycaemia. Consistent with this hypothesis, we demonstrated restoration of defective counterregulatory hormonal responses to hypoglycaemia (referred to as dishabituation) in a rodent model of IAH following introduction of a novel stress stimulus (high intensity training [HIT]). In this proof-of-concept study we sought to further test this hypothesis by examining whether a single episode of HIT would amplify counterregulatory responses to subsequent hypoglycaemia in people with type 1 diabetes who had IAH (assessed by Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating (DAFNE) hypoglycaemia awareness rating 2 or 3). The primary outcome was the difference in adrenaline response to hypoglycaemia following both a single episode of HIT and rest. Methods In this randomised, crossover study 12 participants aged between 18 and 55 years with type 1 diabetes for ≥5 years and an HbA 1c <75 mmol/mol (9%) were recruited. Individuals were randomised using computer generated block randomisation to start with one episode of HIT (4 × 30 s cycle sprints [2 min recovery] at 150% of maximum wattage achieved during V O 2peak assessment) or rest (control). The following day they underwent a 90 min hyperinsulinaemic-hypoglycaemic clamp study at 2.5 mmol/l with measurement of hormonal counterregulatory response, symptom scores and cognitive testing (four-choice reaction time and digit symbol substitution test). Each intervention and subsequent clamp study was separated by at least 2 weeks. The participants and investigators were not blinded to the intervention or measurements during the study. The investigators were blinded to the primary outcome and blood analysis results. Results All participants (six male and six female, age 19-54 years, median [IQR] duration of type 1 diabetes 24.5 [17.3-29.0] years, mean [SEM] HbA 1c 56 [3.67] mmol/mol; 7.3% [0.34%]) completed the study (both interventions and two clamps). In comparison with the rest study, a single episode of HIT led to a 29% increase in the adrenaline (epinephrine) response (mean [SEM]) (2286.5 [343.1] vs 2953.8 [384.9] pmol/l); a significant increase in total symptom scores (Edinburgh Hypoglycaemia Symptom Scale: 24.25 [2.960 vs 27.5 [3.9]; p<0.05), and a significant prolongation of four-choice reaction time (591.8 [22.5] vs 659.9 [39.86] ms; p<0.01] during equivalent hypoglycaemia induced the following day.Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-019-05076-5) contains peer-reviewed but unedited supplementary material, which is available to authorised users.Conclusion...

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“…The side effects of hypoglycemia are abundant and often severe; hypoglycemia has been shown to severely impair cognitive executive functions in both diabetic and healthy controls when tested with hyperinsulinemic hypoglycemic clamps (47). In 22 healthy volunteers, seven out of 12 cognitive tests were abnormal at 2.9 mmol/l glucose, and all of the tests were abnormal at 2.5 mmol/l glucose (48).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Hypoglycemia in everyday life after gastric bypass and duodenal switch

Abrahamsson

Engström

Sundbom

et al. 2015

European Journal of Endocrinology

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Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (!3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P!0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

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Acute Hypoglycemia Impairs Executive Cognitive Function in Adults With and Without Type 1 Diabetes

Cited by 67 publications

References 38 publications

Cognitive costs of reproduction: life‐history trade‐offs explain cognitive decline during pregnancy in women

Cognitive costs of reproduction: life‐history trade‐offs explain cognitive decline during pregnancy in women

A randomised controlled study of high intensity exercise as a dishabituating stimulus to improve hypoglycaemia awareness in people with type 1 diabetes: a proof-of-concept study

Hypoglycemia in everyday life after gastric bypass and duodenal switch

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