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 < 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 < 0.001). The glycentic 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.

Dynamics of blood electrolytes in repeated hyper- and/or hypoglycaemic events in patients with type 1 diabetes

“…The insulin-induced stimulation of the Na + /K + pump readily explains the sharp drop in K + levels seen both at the onset of hypoglycaemia in protocol 2 and the termination of hyperglycaemia in both protocols. In hypoglycaemia, an adrenaline-induced stimulation of the Na + /K + pump may also contribute [7,20]. These results are also consistent with the fast action of insulin on K + levels reported by Petersen et al [7].…”

Influences of protein to energy ratios in breakfast on mood, alertness and attention in the healthy undergraduate students

“…These differences were most pronounced at 0 min, 60 min and 240 min after test meal ingestion. Because the brain is very sensitive to changes in nutrient supply, small metabolic changes may influence behavior performance [34]. An 'inverted U'-shaped dose-response curve was reported for the effects of plasma glucose [35], and insulin concentration [36] on cognitive functions.…”

“…It is likely that the ascending or descending part of an 'inverted U' relation represents the acute positive and negative effects of a rise or fall [37,38] in blood glucose concentration on specific cognitive functions. However, constant metabolic conditions [39] might optimize overall cognitive performance [34,27] for a longer time period. The plasma glucose concentration remained nearly constant after the HP meal in present study.…”

Long-term recovery from unawareness, deficient counterregulation and lack of cognitive dysfunction during hypoglycaemia, following institution of rational, intensive insulin therapy in IDDM

“…It is likely that recurrent hypoglycaemic episodes increase the rate of glucose transport through the blood-brain barrier, and minimize neuroglycopaenia which normally occurs when plasma glucose concentration decreases below normal post-absorptive values [27,28,30], as suggested by studies in rats [34] and more recently in humans [35]. Thus, minimal neuroglycopenia after recurrent hypoglycaemia reduces the hormone and symptom responses which would otherwise occur at precise glycaemic thresholds [27,28,30,36,37].…”