SEARCH · PubMed Health

Results for “hypoglycaemia”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed1996

Definition of neonatal hypoglycaemia: is there a change?

OBJECTIVE: To compare the definitions of neonatal hypoglycaemia in textbooks and among paediatricians in 1992 with those used in 1986. METHODOLOGY: A questionnaire was sent to 420 neonatal paediatricians in the UK and to 88 Australian neonatal paediatricians in 1992 asking for their definition of hypoglycaemia in term babies and preterm/small-for-gestational-age (SGA) babies. Fourteen textbooks on neonatal paediatrics (published since 1990) were also surveyed for the definition of hypoglycaemia used in the text. The UK paediatricians were also asked, 'Do you believe that a baby who is hypoglycaemic but has no abnormal clinical signs is at less risk of neurological damage than a baby who is hypoglycaemic with abnormal signs?' The 1992 results were compared with the published results of a similar survey in 1986. RESULTS: There was a 68% response from neonatal paediatricians both in the UK and Australia. Similar to the 1986 results there continued in 1992 to be a wide range in the definition for hypoglycaemia (< 1(-4) mmol/L) among neonatal paediatricians and in textbooks. The median of the definition of hypoglycaemia for both term and preterm/SGA babies among paediatricians and in textbooks in 1992 was significantly different from the results in 1986. Compared with 1986 there was a significant increase in 1992 in the number of paediatricians and textbooks defining a safe blood glucose concentration as being at least 2 mmol/L Sixty per cent of UK neonatal paediatricians believe that a baby who is hypoglycaemic but has no abnormal clinical signs is at less risk of neurological damage than a baby who is hypoglycaemic with abnormal signs. CONCLUSIONS: From 1986 to 1992 there was a significant change in the definition of hypoglycaemia both among paediatricians and in neonatal textbooks compared with the definition in use during 1965-88. The findings suggest that neonatal paediatricians do change in their practice. The changes in the definition of hypoglycaemia may be due to the data available and discussion on hypoglycaemia since 1988. Neonatal paediatricians still attach significance to clinical signs associated with hypoglycaemia.

Australia↗

PubMed1995

Frequency, severity and symptomatology of hypoglycaemia: a comparative trial of human and porcine insulins in type 1 diabetic patients.

A randomized, double-blind, cross-over trial was performed to compare the frequency, severity, and symptomatology of hypoglycaemia during treatment with porcine and human insulins. Forty patients with Type 1 diabetes (20 newly diagnosed and 20 with diabetes of 5-20 years duration) were treated with human and porcine insulins for consecutive 3-month periods, in random order. Episodes of hypoglycaemia were recorded prospectively with self-reporting of the presence and intensity of symptoms using a standardized scoring technique. Serial measurements of glycated haemoglobin and review of home blood glucose tests confirmed that similar glycaemic control was achieved with each insulin species. On comparison of the treatment periods with human and porcine insulins, no differences were demonstrated in the total frequency of symptomatic hypoglycaemia (3.10 vs 3.06 episodes patient-1 3-months-1; p = 0.94), the frequency of severe hypoglycaemia (0.1 vs 0.2 episodes patient-1 3-months-1; p = 0.44), the occurrence of asymptomatic biochemical hypoglycaemia (0.75 vs 0.68 episodes patient-1 3-months-1; p = 0.81), and the capillary blood glucose concentration at the onset of hypoglycaemic symptoms (2.6 +/- 0.2 vs 2.4 +/- 0.3 mmol l-1; p = 0.40), with all results being expressed for human vs porcine treatment periods, respectively. The symptoms of hypoglycaemia did not differ during the treatment periods with each insulin species. In conclusion, treatment with human insulin had no effect upon the symptomatic response to hypoglycaemia, did not increase the total frequency of hypoglycaemia, and did not emerge as a significant risk factor for severe hypoglycaemia in these patients.

Adult↗

PubMed1996

Nocturnal hypoglycaemia and sleep disturbances in young teenagers with insulin dependent diabetes mellitus.

OBJECTIVE: To determine the effect of nocturnal hypoglycaemia on sleep architecture in adolescents with insulin dependent diabetes mellitus (IDDM). DESIGN: 20 adolescents with IDDM (mean age 12.8 years, mean glycated haemoglobin (HbA1c) 8.9%) were studied on one night. Plasma glucose was measured every 30 minutes and cortisol and growth hormone levels every 60 minutes. Sleep was recorded using standard polysomnographic montages, and sleep architecture was analysed for total sleep time, stages 1-4, rapid eye movement, fragmentation, and arousals. RESULTS: Six subjects (30%) became hypoglycaemic (five subjects < 2.5 mmol/l), with one being symptomatic. There were no differences in age, HbA1c, duration of diabetes, or insulin regimen between hypoglycaemic and non-hypoglycaemic subjects. Hypoglycaemia was not predicted by glucose measurements before bed. There was no detectable rise in plasma cortisol or growth hormone concentrations during hypoglycaemia. Sleep architecture was not disturbed by nocturnal hypoglycaemia with no differences found in sleep stages, fragmentation, or arousals. CONCLUSIONS: Nocturnal hypoglycaemia is a common and usually asymptomatic complication of treatment in adolescents with IDDM. Moderate hypoglycaemia has not been shown to affect sleep architecture adversely. These findings are consistent with, and may explain, the observation that severe hypoglycaemia, with consequent seizure activity, is more common at night than during the day. Counterregulatory hormone responses to nocturnal hypoglycaemia may be less marked than with similar degrees of diurnal hypoglycaemia.

Adolescent↗

PubMed2005

Hypoglycaemia and Russell-Silver syndrome.

AIM: To determine both the incidence and aetiology of chronic hypoglycaemia in symptomatic children with Russell-Silver syndrome (RSS) during the first four years of life. STUDY DESIGN: Twenty-four children with RSS under the age of 4 years, who had either clinical symptoms of hypoglycaemia or previous evidence of biochemically documented hypoglycaemia, were admitted to hospital for 48 hours to perform a 24-h cortisol/glucose profile and a diagnostic fast in those who did not develop spontaneous hypoglycaemia. A dietary assessment was also performed. Glucose profile was assessed in 20 children and cortisol profile in 16; combined glucose and cortisol profile in 15 children. Eight children had a diagnostic fast. Mean chronological age at time of assessment was 2.2 +/- 0.8 years (range 1.1-3.9 years). RESULTS: Ten of 24 children had previously been documented as having hypoglycaemia. Seven of 12 patients were growth hormone (GH) insufficient after a glucagon test. Their feeding pattern was described as 'poor and picky eaters' in all, seven requiring nasogastric tube feeding. The mean spontaneous energy intake (n = 8) was 56 +/- 19.6 kcal/kg/day (range 38-90). Nocturnal sweating was the commonest symptom (23.96%), followed by irritability (11.46%), tantrums (7.29%), pallor and shakiness (3.13%). The glucose profile in seven children showed hypoglycaemia but only four were symptomatic. None of the children was cortisol deficient. The mean period of fasting was 11.8 +/- 4 hours (range 3-18 h). No metabolic/hormonal abnormality, with the exception of GH insufficiency, was detected at the time of hypoglycaemia. CONCLUSION: Children with RSS are prone to develop spontaneous hypoglycaemia especially if they are not fed both frequently and regularly. The most likely explanation is accelerated starvation and/or GH insufficiency. We suggest guidelines to minimise hypoglycaemia in these children.

Appetite↗

PubMed1999

Propranolol in hypoglycaemia unawareness.

The effect of propranolol on the occurrence of hypoglycaemic symptoms was assessed in insulin-dependent diabetic patients with hypoglycaemia unawareness. A double-blind, randomised parallel group study (2:1 fashion) was conducted over 4-week period. The propranolol group (n = 9) received 20 mg (week 1 and 2) and 30 mg (week 3 and 4) twice daily, and the other group (n = 5) a matched placebo for 4 weeks. Patients included had experienced at least two severe hypoglycaemic episodes (coma or seizures) during the previous year, which were characterised by a lack of adrenergic symptoms and required the assistance of another person. The mean number of hypoglycaemias during the study period was similar in both groups (placebo: 13 +/- 2 propranolol: 11 +/- 1), whereas the number of totally asymptomatic hypoglycaemias (< 0.6 g/l) was lower on propranolol than on placebo (3 +/- 1 vs 8 +/- 3, NS) and the number of symptomatic hypoglycaemias was higher (7.2 +/- 2 vs 4.6 +/- 1, NS). Subjective evaluation of treatment by the investigators showed 0/5 successes in the placebo group and 5/9 in the propranolol group (chi2 = 4.32, p = 0.038). The main advantage of propranolol over placebo was an increased incidence of sweating. The ratio [number of hypoglycaemias with sweating/total number of hypoglycaemias] being higher with propranolol (0.28 +/- 0.08 vs 0.06 +/- 0.02, p = 0.06). This pilot study suggests that beta-blockers may be useful in restoring adrenergic symptoms during hypoglycaemia in insulin-dependent diabetic patients without warning symptoms of hypoglycaemia. This beneficial effect seems to be predominantly related to an increase in hypoglycaemia-induced sweating. A larger study is needed to confirm or invalidate these preliminary results.

Adrenergic beta-Antagonists↗

PubMed1997

Hypoglycaemia and non-cognitive aspects of psychological function in insulin-dependent (type 1) diabetes mellitus (IDDM).

Hypoglycaemia provokes unpleasant symptoms and sensations in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). There is much interest in, and information on, the cognitive effects of acute insulin-induced hypoglycaemia. However, the effects of hypoglycaemia on brain function extend to important, non-cognitive aspects of psychological functioning, which are reviewed here. Acute hypoglycaemia induces changes in mood which result in a transient state of 'tense tiredness', a decrease in happiness, an increase in tense arousal, and decreased energetic arousal. Appraisals of life problems are affected adversely. Frequent exposure to hypoglycaemia is associated with heightened fear of hypoglycaemia, which can be quantitated in individuals. Personality may also influence behavioural responses to hypoglycaemia and the ability of an individual to cope with diabetes. The adverse effects of hypoglycaemia on mood, behaviour, personality, social function and management of diabetes in individual patients may be profound and need to be identified and addressed appropriately.

Diabetes Mellitus, Type 1↗

PubMed1997

Altered ventricular repolarization during hypoglycaemia in patients with diabetes.

There is circumstantial evidence implicating hypoglycaemia in the sudden overnight death of young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM), the mechanism of which is unknown. We have investigated the effects of hypoglycaemia on the electrocardiogram in 15 patients with diabetes (8 with IDDM and 7 with NIDDM) using a high resolution computer-based system. Patients were randomized to either 2 h of euglycaemia or hypoglycaemia (at around 3 mmol l(-1)) during the afternoon, using hyperinsulinaemic glucose clamps, the two visits separated by a period of at least 4 weeks. Corrected QT interval (QTc), plasma potassium, and adrenaline were measured at baseline and at 0, 60, and 120 min. The degree of QTc lengthening (from baseline) during clamped hypoglycaemia was greater compared to the euglycaemic control period in patients with IDDM (median[range] at 60 min, 156[8 to 258] vs 6[-3 to 28] ms, p <0.02) and NIDDM (120 min, 128[16 to 166] vs 4[-3 to 169] ms, p <0.05). The fall in plasma potassium was greater during clamped hypoglycaemia compared to euglycaemia in those with NIDDM (p <0.03) but not in those with IDDM (p> 0.06). The rise in plasma adrenaline was greater during clamped hypoglycaemia in both groups (IDDM p <0.02, NIDDM p <0.02) and there was a strong relationship between the rise in adrenaline and increase in QTc (r = 0.73, p <0.0001). These data demonstrate alteration of ventricular repolarization with lengthening of the QT interval during hypoglycaemia and suggest a possible mechanism by which hypoglycaemia could cause ventricular arrhythmias.

Adult↗

PubMedDate not supplied

Evaluation of serum markers of neuronal damage following severe hypoglycaemia in adults with insulin-treated diabetes mellitus.

BACKGROUND: Neurone-specific enolase (NSE) and protein S-100 (S-100) may be used as markers of acute neuronal damage in humans with neurological disorders. METHOD: To evaluate their use following a single episode of severe hypoglycaemia (defined as an episode requiring external assistance to aid recovery), serum concentrations of NSE and S-100 were measured following hypoglycaemia which had not caused persistent neurological impairment in 16 patients with insulin-treated diabetes (the 'hypo' subjects), and in three diabetic patients who died following severe hypoglycaemia. The serum proteins were also measured in 10 subjects with insulin-treated diabetes who had not experienced an episode of severe hypoglycaemia within the preceding year (the 'control' subjects). RESULTS: No differences in serum concentrations of NSE and S-100 were observed between the 'control' and the 'hypo' subjects at either 36 hours or seven days after the episode of severe hypoglycaemia (p>0.05). However, in two of the three subjects who died following hypoglycaemia, serum concentrations of the markers were markedly elevated. CONCLUSIONS: Any neuronal injury occurring during severe hypoglycaemia that is not associated with persistent neurological deficit is insufficient to provoke elevation of these serum markers. However, the measurement of serum concentrations of NSE and S-100 may have a prognostic role in evaluating clinical outcome following severe hypoglycaemia which is associated with neurological damage.

Adult↗

PubMedDate not supplied

Biological and behavioural determinants of the frequency of mild, biochemical hypoglycaemia in patients with Type 1 diabetes on multiple insulin injection therapy.

BACKGROUND: Severe hypoglycaemic episodes are an important source of morbidity in people with Type 1 diabetes. The occurrence of severe hypoglycaemia is strongly related to the frequency of low blood glucose readings. The aim of this exploratory study was to identify determinants of the frequency of mild, biochemical hypoglycaemia in patients with Type 1 diabetes treated with multiple insulin injection therapy. METHODS: We studied 31 patients with Type 1 diabetes in reasonable glycaemic control (HbA(1c)</=8.3%) during multiple injection therapy. The study had a prospective, observational design. We used standardised home blood glucose monitoring (HBGM) diaries to assess the frequency of hypoglycaemia (HBGM readings<3.5 mmol/L) over a period of 6 weeks. Potential determinants studied included biological factors, self-management factors (including weekly total physical activity and vigorous physical activity), psychological factors (including psychological distress) and mediating factors [average and standard deviation (SD) of the HBGM readings and self-reported hypoglycaemia awareness]. RESULTS: Determinants of mild hypoglycaemia frequency identified in univariate regression analyses were: SD and mean of HBGM (beta 0.6, p=0.001 and beta -0.6, p=0.001), diabetes duration (beta 0.5, p=0. 008) and self-reported hypoglycaemia unawareness (beta -0.5, p=0. 003). A trend was observed for performance of vigorous physical activities (beta 0.3, p=0.06) and external eating behaviour (beta -0. 3, p=0.1). These relations were confirmed in multivariate analyses. CONCLUSIONS: Patients with Type 1 diabetes who have a high blood glucose variability and low average blood glucose concentration, diabetes of long duration, low body mass index, self-reported impaired awareness of hypoglycaemia and those participating in vigorous physical activities, specifically require interventions aimed at preventing hypoglycaemia.

Adult↗

PubMedDate not supplied

Recall of severe hypoglycaemia and self-estimated state of awareness in type 1 diabetes.

BACKGROUND: The ability of people with insulin-treated diabetes to remember severe hypoglycaemia and the consistency of their self-estimated awareness of hypoglycaemia are not well documented but are important in clinical practice. The aim of this study is to assess recall of severe hypoglycaemia in patients with type 1 diabetes and to evaluate the feasibility of a simple method for clinical classification of the awareness of hypoglycaemia. METHODS: A one-year prospective study was performed on a cohort of patients with type 1 diabetes (n = 230). The rate of severe hypoglycaemia reported retrospectively at the end of the study was compared to the prospectively recorded rate during the study period. Self-estimated awareness was explored in questionnaires at baseline and at the end, and assessments were evaluated by the occurrence of severe hypoglycaemic episodes. RESULTS: Almost 90% of the participants correctly recalled whether they had had severe hypoglycaemia. However, those with high prospectively recorded numbers had incomplete recall, resulting in a 15% underestimation of the overall rate. On the basis of the answer to the question "Do you recognise symptoms when you have a hypo?", the population was classified into three groups: 40% with normal awareness, 47% with impaired awareness and 13% with unawareness. The groups with impaired awareness and unawareness had 5.1 and 9.6 times higher rates of severe hypoglycaemia, respectively, compared to the group with normal awareness (p < 0.001). CONCLUSION: People with type 1 diabetes generally remember severe hypoglycaemic episodes during a one-year period. A simple method is proposed for classifying the state of awareness of hypoglycaemia in clinical practice.

Age of Onset↗

PubMed1994

Physiological response to postural change during mild hypoglycaemia in patients with IDDM.

It has been suggested that patients with insulin-dependent diabetes mellitus may be less aware of impending hypoglycaemia when lying than standing. We have studied the effect of posture and duration of hypoglycaemia on symptoms and physiological responses in 10 men with insulin-dependent diabetes. A standard tilting protocol was used (supine, 50 degrees, 90 degrees headup, and return to supine, 5 min at each position). At one visit patients were tilted before, 10 min after and 40 min after achieving hypoglycaemia (blood glucose 2.5 mmol/l), and at another visit were tilted after euglycaemia (5.0 mmol/l) using a hyperinsulinaemic clamp. At each position, hormonal and physiological responses and symptoms (using visual analogue scales) were recorded. After 10 min of hypoglycaemia, adrenaline was significantly higher when 90 degrees headup compared with supine (mean [+/- SEM] 6.26 [+/- 1.88] vs 1.68 [+/- 0.4] nmol/l; p < 0.05), and fell significantly (to 2.46 [+/- 0.65] nmol/l; p < 0.05) when returned to supine; sweating, symptom score and blood pressure followed a similar pattern. After 40 min of hypoglycaemia a similar effect of standing was seen on sweating, adrenaline and blood pressure but symptoms did not increase. Five patients underwent two further periods of hypoglycaemia, remaining supine or standing throughout. Face skin blood flow (p < 0.05) and temperature (p = 0.05) decreased when standing was maintained compared with lying. In conclusion, standing increases awareness of early hypoglycaemia and modifies many of the physiological changes. This increase in awareness is lost if hypoglycaemia is prolonged.

Adult↗

PubMed1995

Regional cerebral blood flow during hypoglycaemia in children with IDDM.

Hypoglycaemia may cause transient cognitive impairment and neurological deficits that are frequently unilateral. The effect of mild hypoglycaemia (serum glucose level 3.4 +/- 0.1 mmol/l; mean +/- SEM) on regional cerebral blood flow and cerebrovascular resistance was studied in eight right-handed children with insulin-dependent diabetes mellitus (age 14.9 +/- 0.7 years; diabetes duration 7.4 +/- 1.1 years; six males) using the intravenous xenon-133 clearance method. Global mean cerebral grey and white matter blood flow, adjusted to mean pCO2 of cohort, showed a trend towards an increase from 54.7 +/- 3.5 ml.100 g-1.min-1 at baseline euglycaemia to 58.0 +/- 4.1 ml.100 g-1.min-1 during hypoglycaemia (p = 0.075). Statistically significant changes were seen in global mean cerebral grey matter blood flow, as indexed by initial slope, which increased from 88.0 +/- 6.5 min-1 before hypoglycaemia to 96.3 +/- 7.2 min-1 during hypoglycaemia (p < 0.05). Cerebral grey matter blood flow was significantly higher in the right hemisphere compared to the left during hypoglycaemia (p < 0.01) but not at baseline euglycaemia. Measurements of global cerebrovascular resistance showed a borderline decrease from 1.64 +/- 0.11 to 1.54 +/- 0.11 mm Hg.ml-1.100 g-1.min-1 (p < 0.09). In conclusion, mild hypoglycaemia is associated with increases in cerebral blood flow which are greater in grey matter flow indices and in the right hemisphere. We speculate that asymmetrical cerebral blood flow changes may explain the frequent laterality of neurological deficits during severe hypoglycaemia.

Adolescent↗

PubMed1990

Permanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man.

Seventeen Type 1 (insulin-dependent) diabetic patients with a history of recurrent and severe hypoglycaemia and Type 1 diabetic patients with no severe hypoglycaemia were compared as regarded performances in tests of neuropsychological functioning. To test the hypothesis that recurrent severe hypoglycaemia gives rise to permanent cognitive impairment, the study group was selected among those patients who had met with repeated attacks over the last three years or more as identified by a questionnaire among almost 600 insulin-treated diabetic patients. The comparison group without known severe reactions were comparable to the study group with respect to type of diabetes, sex, age, age at onset, duration of diabetes, socio-economic parameters, and prevalence of neuropathy and retinopathy. The results indicate that Type 1 diabetic patients with recurrent severe hypoglycaemia scored lower than those without severe hypoglycaemia in tests of motor ability, short-term and associative memory and visuospatial tasks assessing ability in general problem-solving. Type 1 diabetic patients with severe hypoglycaemia also displayed a higher frequency of perspective reversals suggesting frontal-lobe involvement. These data can be interpreted in two ways. One interpretation implies that the cognitive impairment of Type 1 diabetic patients with severe hypoglycaemia reflects a selection factor, the other that recurrent episodes of severe hypoglycaemia result in permanent cognitive impairment.

Cognition↗

PubMed2002

Hypoglycaemia unawareness and the brain.

The intention of this paper is to critically review the current state of knowledge of the role of the brain in the syndrome of hypoglycaemia unawareness. Both the role of the brain in the detection of hypoglycaemia and initiation of the counterregulatory responses and the function of the cerebral cortex during acute hypoglycaemia are considered. The evidence for and against the brain as the primary site of mammalian hypoglycaemia sensing and the mechanisms whereby such sensing may occur and change in hypoglycaemia unawareness are discussed. Current evidence supports a major role for the central nervous system in hypoglycaemia sensing and there is increasing understanding of the mechanisms of counterregulatory failure and cognitive dysfunction in hypoglycaemia unawareness. More needs to be done to expand this understanding and translate it into therapeutic strategies to defend against severe hypoglycaemia in diabetes therapy.

Aging↗

PubMed2002

Rate of fall of blood glucose and physiological responses of counterregulatory hormones, clinical symptoms and cognitive function to hypoglycaemia in Type I diabetes mellitus in the postprandial state.

AIMS/HYPOTHESIS: The aim of this study was to establish the effect of a rate of decreasing plasma glucose concentrations on responses to hypoglycaemia, i.e. release of counterregulatory hormones, perception of symptoms, deterioration of cognitive function, and rates of forearm noradrenaline spillover, in the postprandial condition and in the sitting position. METHODS: We studied 11 subjects with Type I (insulin-dependent) diabetes mellitus, twice during clamped insulin-induced hypoglycaemia (2.4 mmol/l) after eating in the sitting position. On one occasion, plasma glucose was decreased at the rate of 0.1+/-0.003 mmol x min(-1) x l(-1) (fast fall), on the other at the rate of 0.03+/-0.001 mmol x min(-1) x l(-1) (slow fall). Subjects underwent a control euglycaemic clamp study as well. RESULTS: In response to fast-fall as compared to slow-fall hypoglycaemia, which was about 30 min longer, cognitive tasks were performed as follows: Trail-Making B, PASAT 2 s, Digit Vigilance Test and Verbal Memory deteriorated more, adrenaline increased less (2.8+/-0.5 vs 3.5+/-0.7 nmol/l, p=0.03), forearm noradrenaline spillover was greater (6.5+/-1.0 vs 5.2+/-0.4 pmol x min(-1) x 100 ml(-1), p=0.04), and symptoms were no different. After recovery from hypoglycaemia, cognitive function was still deteriorated compared to the baseline with no difference between fast and slow-fall hypoglycaemia. The evident response of glucagon to postprandial hypoglycaemia contrasted with the blunted or absent response in the fasting state. CONCLUSION/INTERPRETATION: In the postprandial condition and sitting position, fast-fall hypoglycaemia is more dangerous than slow-fall, because it deteriorates cognitive function more, and activates responses of counterregulatory hormones less than slow-fall hypoglycaemia.

Adult↗

PubMed2004

Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes.

AIMS/HYPOTHESIS: Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. METHODS: We studied 22 patients with Type 1 diabetes (mean age 40.4+/-17.2 years, duration of diabetes 17.2+/-9.3 years, HbA1c 8.2+/-1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. RESULTS: Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (+/-15) above baseline, compared with 9 ms (+/-19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (+/-0.21) above baseline during hypoglycaemia, compared with -0.05 nmol/l (+/-0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. CONCLUSION/INTERPRETATION: QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia.

Adult↗

PubMed2004

Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes.

AIMS/HYPOTHESIS: It has been postulated that hypoglycaemia-related cardiac dysrhythmia and, in particular, prolonged cardiac repolarisation, may contribute to increased mortality rates in children and adolescents with type 1 diabetes. METHODS: We examined the prevalence of prolonged QT interval on ECG during spontaneous hypoglycaemia in 44 type 1 diabetic subjects (aged 7-18 years), and explored the relationships between serial overnight measurements of QT interval corrected for heart rate (QTc) and serum glucose, potassium and epinephrine levels. Each subject underwent two overnight profiles; blood was sampled every 15 min for glucose measurements and hourly for potassium and epinephrine. Serial ECGs recorded half-hourly between 23.00 and 07.00 hours were available on 74 nights: 29 with spontaneous hypoglycaemia (defined as blood glucose <3.5 mmol/l) and 45 without hypoglycaemia. RESULTS: Mean overnight QTc was longer in females than in males (412 vs 400 ms, p=0.02), but was not related to age, diabetes duration or HbA(1)c. Prolonged QTc (>440 ms) occurred on 20 out of 74 (27%) nights, with no significant differences between male and female subjects, and was more prevalent on nights with hypoglycaemia (13/29, 44%) than on nights without (7/45, 15%, p=0.0008). Potassium levels were lower on nights when hypoglycaemia occurred (minimum potassium 3.4 vs 3.7 mmol/l, p=0.0003) and were inversely correlated with maximum QTc (r=-0.40, p=0.03). In contrast, epinephrine levels were not higher on nights with hypoglycaemia and were not related to QTc. CONCLUSIONS/INTERPRETATION: In young type 1 diabetic subjects, prolonged QTc occurred frequently with spontaneous overnight hypoglycaemia and may be related to insulin-induced hypokalaemia.

Adolescent↗

PubMed2005

Hypothalamic AMP-activated protein kinase mediates counter-regulatory responses to hypoglycaemia in rats.

AIMS/HYPOTHESIS: Appropriate counter-regulatory hormonal responses are essential for recovery from hypoglycaemia. Although the hypothalamus is known to be involved in these responses, the molecular mechanisms have not been fully elucidated. AMP-activated protein kinase (AMPK) functions as a cellular energy sensor, being activated during energy depletion. As AMPK is expressed in the hypothalamus, an important site of neuroendocrine regulation, the present study was undertaken to determine whether hypothalamic AMPK mediates counter-regulatory responses to hypoglycaemia. MATERIALS AND METHODS: Hypoglycaemia was induced by i.p. injection of regular insulin (6 U/kg) in Sprague-Dawley rats. Hypothalamic AMPK phosphorylation and activities were determined 1 h after i.p. insulin injection. To investigate the role of hypothalamic AMPK activation in mediating counter-regulatory responses, an AMPK inhibitor, compound C, was pre-administered intracerebroventricularly (i.c.v.) or dominant-negative (DN)-AMPK was overexpressed in the hypothalamus before induction of hypoglycaemia. RESULTS: Insulin-induced hypoglycaemia increased hypothalamic AMPK phosphorylation and alpha2-AMPK activities in rats. The change was significant in the arcuate nucleus/ventromedial hypothalamus (ARC/VMH) and paraventricular nuclei (PVN). Prior i.c.v. administration of compound C attenuated hypoglycaemia-induced increases in plasma concentrations of corticosterone, glucagon and catecholamines, resulting in severe and prolonged hypoglycaemia. ARC/VMH DN-AMPK overexpression impaired early counter-regulation, as evidenced by reduced glucagon and catecholamine responses. In contrast, PVN DN-AMPK overexpression attenuated late counter-regulation and corticosterone responses. CONCLUSIONS/INTERPRETATION: Systemic hypoglycaemia causes hypothalamic AMPK activation, which is important for counter-regulatory hormonal responses. Our data indicate that hypothalamic AMPK acts as a fuel gauge, sensing the whole-body energy state and regulating not only energy homeostasis but also neuroendocrine functions.

AMP-Activated Protein Kinases↗