Prevalence of nocturnal hypoglycemia in first trimester of pregnancy in patients with insulin treated diabetes mellitus.

BACKGROUND: Excellent metabolic control before conception and during diabetic pregnancies is the aim in order to avoid malformations and perinatal morbidity. Since an inverse correlation between median blood glucose concentration (BG) and hypoglycemia as well as a high prevalence of nocturnal hypoglycemia have been described, we investigated the frequency of nocturnal hypoglycemia and the predictive value of bedtime blood glucose concentration for development of this condition in insulin treated diabetic patients. METHODS: During hospitalization, with no other changes in the patients' normal schedules, hourly blood samples were drawn from an iv-cannula from 22.00 h to 07.00 h for one night. BG (venous whole blood) and hemoglobin A1c were determined the following day. RESULTS: Fifty-three patients participated; subsequently ten were excluded due to discontinuation of blood sampling during the night, caused by either discomfort or cannula problems. Of the remaining 43 patients, 16 (37%) had at least one blood glucose <3.0 mmol/l. The duration of hypoglycemia was 2.4 (1-7) h with the highest prevalence at 05 h. Only one patient felt hypoglycemic during the night. Hemoglobin A1c was similar in patients with (7.1+/-1.2%, mean+/-s.d.) and without (6.8+/-0.8%) nocturnal hypoglycemia. Women with nocturnal hypoglycemia had significantly lower BG before bedtime compared to patients without hypoglycemia, 6.4+/-3.6 mmol/l vs. 7.9+/-2.4 mmol/l, p<0.05. The best predictive value for nocturnal hypoglycemia was a BG below 6.0 mmol/l at 23.00, which resulted in a risk of nocturnal hypoglycemia of 71%. Conversely, if the BG was > or =6.0 mmol/l, the chance of avoiding nocturnal hypoglycemia was 83%. CONCLUSION: Nocturnal hypoglycemia was seen with a prevalence of 37% during a night in the first trimester of pregnancy in insulin treated patients. Only one patient registered the hypoglycemia. Nocturnal hypoglycemia could be predicted in the majority of patients by measurements of BG before bedtime.

Detection of EEG patterns related to nocturnal hypoglycemia.

The aim of the project was to detect specific EEG patterns related to hypoglycemia. EEG analysis was performed using a probabilistic classifier and unsupervised learning for the construction of learning sets for the classifier. Unsupervised learning and additional tools were used in the search for EEG patterns occurring when the blood-glucose level was below the hypoglycemic threshold. The rate of these specific EEG patterns was below 5% in normal nights. In patients who were known to have no or a reduced glucagon response to hypoglycemia, the rate increased to 20-80%.

Nocturnal versus diurnal hormonal counterregulation to hypoglycemia in type 1 (insulin-dependent) diabetic patients.

UNLABELLED: Asymptomatic hypoglycemia in IDDM patients seems to be more frequent during the night than during the day, with reported frequencies as high as 56%. Hormonal counterregulation to diurnal and nocturnal hypoglycemia was studied in 10 insulin-dependent diabetic patients without diabetic complications in order to test whether hormonal responses were lower at night than during daytime. A lower catecholamine response might imply less marked symptoms and therefore one reason why patients are not awakened by hypoglycemia. Blood glucose was stabilized to around 6 mmol/l by iv insulin infusion and hypoglycemia was induced by increasing the insulin infusion rate--in the night studies at 01.30, in the day studies at 08.00. Blood glucose nadirs were 1.5 +/- 0.4 (1.2-1.9) mmol/l at night and 1.9 +/- 0.3 (1.3-2.2) mmol/l during the day; in the three patients the nadirs were identical during both the night and day. One patient had no adrenaline response to daytime hypoglycemia. In general, nocturnal hypoglycemia elicited greater catecholamine responses correlated to the duration of hypoglycemia. Glucagon responses showed a great heterogeneity independently of diabetes duration and hypoglycemic level. Growth hormone secretion was reduced during the night study; however, no refractory periods were found after sleep-related growth hormone secretion. IN CONCLUSION: counter-regulatory hormonal responses tend to be greater at night than during the day and do not explain why patients are not awakened by nocturnal hypoglycemia.

The Diva System, a computerized diary, used in young type 1 diabetic patients.

UNLABELLED: The purpose of the present study was to evaluate the clinical efficiency of a computer bases registration- and analysis-system, Diva System, designed for the support of diabetes care. Fifty six boys aged 14-20 years with a diabetes duration of more than two years and HbA1c above 8% were allocated to one of three groups: 1) Diva group: Diva supported intensified outpatient regimen n = 9, 2) Control group A: Intensified outpatient control n = 7, and 3) Control group B: Conventional outpatient control n = 40. The patients were followed for a period of twelve months, in which the Diva group patients used the system during the first six months. In this period the HbA1c decreased significantly in the Diva group, 1.6% p < 0.001, compared to only a slight decrease in the two control groups, 0.3 and 0.4% respectively, ns. IN CONCLUSION: The Diva System seems to be a supportive tool, which might assist the patients to better self care and thereby to improved metabolic control. However, the use of the computer system is time consuming.

Cognitive function in type 1 (insulin-dependent) diabetic patients after nocturnal hypoglycaemia.

UNLABELLED: Eight Type 1 (insulin-dependent) diabetic patients with no diabetic complications were studied on two consecutive and one subsequent overnight occasions. The aim was to evaluate the influence of nocturnal hypoglycaemia on neuropsychological and reaction time tests the following morning. Hypoglycaemia was induced by i.v. insulin infusion, blood glucose nadir was 1.5 +/- 0.3 mmol/l. Duration of hypoglycaemia (blood glucose less than 3 mmol/l) was 101 +/- 38 min. Whole night sleep statistics for all patients showed no statistical differences between the normoglycaemic and hypoglycaemic nights, however, there was a tendency of prolongation of the second sleep cycle in the nights with hypoglycaemia. Each patient was used as his own control and periods with blood glucose concentration less than 3 mmol/l were compared to exactly the same periods in nights with blood glucose level over 5 mmol/l. During hypoglycaemia the amount of deep sleep was reduced and replaced by superficial sleep and arousals of short duration. Further, the reduction in deep sleep was replaced later at night. Neuropsychological test scores and reaction time measurements in the morning showed no differences between the normoglycaemic and hypoglycaemic nights. IN CONCLUSION: despite sleep disturbances, nocturnal hypoglycaemia did not impair cognitive function the following morning in Type 1 (insulin-dependent) diabetic patients.

Nasal glucagon in the treatment of hypoglycaemia in type 1 (insulin-dependent) diabetic patients.

The aim of this study was to compare the effect of nasally administered glucagon in doses of 1 (A) and 2 mg (B), with 1 mg glucagon administered intramuscularly (C) in 12 C-peptide-negative IDDM patients. Spontaneous recovery (D) from insulin-induced hypoglycaemia in the same patients was used as reference. The mean age was 31.1 (21-48) years, diabetes duration 10.8 (2.7-31) years and HbA1c 7.7 (6.5-9.8)%. Hypoglycaemia was induced by i.v. insulin infusion. When blood glucose (BG) reached about 2 mmol/l either glucagon was administered or the patients recovered spontaneously. BG nadir was 1.6 (1.1-2.3) mmol/l. BG increments during the first 15 min after glucagon administration were: (A) 1.9 +/- 0.7 (0.4-3.0); (B) 2.5 +/- 0.7 (1.5-3.5); (C) 2.5 +/- 1.0 (1.2-4.7); and (D) 0.3 +/- 0.4 (0-1.0) mmol/l, respectively. All treatments were more effective, measured as increments in BG, than spontaneous recovery, P less than 0.00001. There was no difference between nasal treatment with 2 mg (B) and i.m. treatment (C), both being more effective than 1 mg (A) nasal treatment, P less than 0.1. BG continued to increase up to 10 mmol/l 90 min after i.m. glucagon administration, whereas it stabilized at a level of 4.6-6 mmol/l, 30-45 min after nasal administration. Eighty percent of the patients had side-effects to nasal administration - local irritation, rhinitis or sneezing. Half of the patients sneezed, without correlation with the delivered dose of glucagon. None of the patients had side-effects which would preclude further treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Emergency prehospital treatment of severe hypoglycemia in the Copenhagen Municipality. A retrospective analysis of 180 episodes]. / Akut praehospitalsbehandling af svaer hypoglykaemi i Københavns Kommune. En retrospektiv analyse af 180 episoder.

A retrospective study concerning prehospital treatment of 180 consecutive patients with severe hypoglycaemia, treated by the Mobile intensive care unit (MICU) in Copenhagen was performed. A total of 113 (63%) were male. Of these 104 patients had blood-glucose concentrations less than 2 mmol/l. Eleven patients had blood-glucose concentrations between 2 and 4 mmol/l. After treatment with 50% glucose solution: (25-50 ml I.V.), 131 patients could remain at home. During the 24 hour period after the initial event, two patients needed a second treatment by the mobile intensive care unit on account of secondary hypoglycaemia. Four further patients were admitted to hospital; none of these suffered secondary hypoglycaemic events. One case was registered as "life-saving" on account of treatment of severe airway obstruction. It seems that prehospital treatment of severe hypoglycaemia is beneficial mainly because transportation of delirious, abusive patients can be avoided and the workload of emergency-rooms can be reduced. 69% of patients suffering a severe hypoglycaemic event, were treated prehospitally without subsequent transportation to hospital.

Sleep disturbances in IDDM patients with nocturnal hypoglycemia.

Eight insulin-dependent diabetic patients were studied to evaluate sleep patterns during normoglycemia and spontaneous and insulin-induced hypoglycemia. Two channels of electroencephalogram (EEG), electromyogram and actooculogram were recorded. The signals were analyzed off-line, using a polygraphic sleep analysis system. The scoring was mainly based on the color density spectral array of the EEG. Blood glucose and growth hormone were measured serially. Asymptomatic, spontaneous nocturnal hypoglycemia occurred in 38% of the nights. Conventional sleep analysis showed a tendency toward prolongation of the two first rapid eye movement cycles on hypoglycemic nights, although it was insufficient to explain the activities seen during hypoglycemia. Blood glucose values below 2.0 mmol/l were observed in some of the patients accompanied by EEG changes with increased theta and delta activity.

Lens fluorescence in relation to nephropathy in insulin-dependent diabetes mellitus.

The relationship between diabetic nephropathy and blue-green lens fluorescence, lens transmittance, and other lens fluorometry parameters was studied in patients with long-term insulin-dependent diabetes mellitus. The findings in 10 patients who presented with diabetic nephropathy were compared with those of 11 patients of comparable age and duration of diabetes but without nephropathy. Diabetic nephropathy was associated with increased lens fluorescence (P = 0.04) and decreased lens transmittance (P = 0.045). We propose that lens changes may be responsible for various psychophysical abnormalities in diabetic patients and that our results explain the correlation of these abnormalities with the degree of microangiopathy.

Endocrine emergencies. Hypoglycaemia.

Hypoglycaemia is possibly the most frequent metabolic emergency, in that insulin-induced hypoglycaemia is a common side-effect of treatment of a common disease. The symptoms are partly sympathetic and related to the release of catecholamines. These symptoms include sweating, tremor, palpitations, sensation of hunger, restlessness and anxiety. Other symptoms are caused by an insufficient supply of glucose to the brain, resulting in neuroglucopenia with symptoms like blurred vision, weakness, slurred speech, vertigo and difficulties in concentration. Symptom recognition is the primary and most effective defence against cerebral dysfunction which is the ultimate consequence of hypoglycaemia. Even in insulin-treated diabetic patients symptom failure might occur. Patients who experience severe episodes of hypoglycaemia do not constitute a special subgroup of patients. However, near-normalization of blood glucose levels have resulted in an increase in the incidence of severe hypoglycaemia. Moreover, the threshold for hormonal counter-regulatory responses in adrenaline, growth hormone and cortisol is lowered after a period of strict metabolic control in insulin-dependent diabetic patients. The glucose level at which the patients become subjectively aware of hypoglycaemia is correspondingly reduced. Other reasons for hypoglycaemia to occur are oral hypoglycaemic agents, especially sulfonylureas which may be potentiated by other drugs. Prolonged hypoglycaemia may be seen after first-order sulfonylureas, and may indicate glucose infusion as treatment. Next to insulin and sulfonylurea, ethanol is the most common cause of hypoglycaemia. In non-diabetics, hypoglycaemia will typically develop 6-24 h after a moderate or heavy intake of ethanol by a person who has had an insufficient intake of food for 1 or 2 days. Insulin-producing tumours, insulinomas and non-islet cell tumours may also be reasons for hypoglycaemia in non-diabetics. Treatment of mild episodes of hypoglycaemia is intake of fast-absorbing carbohydrates. Severe episodes can be treated with either i.v. dextrose or glucagon injected i.m. or i.v. The glycaemic response and recovery of a normal level of consciousness is 1-2 min slower after glucagon than after glucose.

Nocturnal electroencephalogram registrations in type 1 (insulin-dependent) diabetic patients with hypoglycaemia.

Eight Type 1 (insulin-dependent) diabetic patients with no diabetic complications were studied overnight for two consecutive and one subsequent night with continuous monitoring of electroencephalogram and serial hormone measurements. The aims were: 1) to evaluate the influence of spontaneous and insulin-induced hypoglycaemia on nocturnal electroencephalogram sleep-patterns and, 2) to evaluate counter-regulatory hormone responses. Spontaneous hypoglycaemia occurred on six nights (38%) with blood glucose concentrations less than 3.0 mmol/l and on four nights less than 2.0 mmol/l. All the patients experienced insulin-induced hypoglycaemia with a blood glucose nadir of 1.6 (range 1.4-1.9) mmol/l. The electroencephalogram was analysed by a new method developed for this purpose in contrast to the traditional definition of delta-, theta-, alpha- and beta-activity. The blood glucose concentration could be correlated to the rank of individual electroencephalogram-patterns during the whole night, and specific hypoglycaemic amplitude-frequency patterns could be assigned. Three of the eight patients showed electroencephalogram changes at blood glucose levels below 2.0 (1.6-2.0) mmol/l. The electroencephalogram classes representing hypoglycaemic activity had peak frequencies at 4 and 6 Hz, respectively, clearly different from the patients' delta- and theta-activity. The changes were not identical in each patient, however, they were reproducible in each patient. The changes were found equally in all regions of the brain. The three patients with electroencephalogram changes during nocturnal hypoglycaemia could only be separated from the other five patients by their impaired glucagon responses. Against this background the possibility of protection by glucagon, against neurophysiologic changes in the brain during hypoglycaemia may be considered.

Symptomatic hypoglycaemia in 411 type 1 diabetic patients.

The frequency of symptomatic hypoglycaemic episodes was studied in 411 randomly selected conventionally treated Type 1 diabetic out-patients. Between two consecutive visits to the out-patient clinic each patient filled in a questionnaire at home. The number of hypoglycaemic episodes was then recorded prospectively in a diary for 1 week. From the questionnaires, the (retrospective) frequencies of mild and severe symptomatic hypoglycaemia were 1.6 and 0.029 episodes patient-1 week-1. From the diaries, the (prospective) frequencies of mild and severe hypoglycaemic episodes were 1.8 and 0.027 patient-1 week-1. Symptomatic hypoglycaemia was more frequent on working days than during weekends (1.8:1) and more frequent in the morning than during the afternoon, evening, and night (4.5:2.2:1.4:1). The symptoms of hypoglycaemia were non-specific, heterogeneous, and weakened with increasing duration of diabetes. During their diabetic life, 36% of the patients had experienced hypoglycaemic coma. The frequency of hypoglycaemia was positively, but only weakly, correlated with insulin dose, number of injections, percentage unmodified insulin of the total dose, and HbA1c (mild hypoglycaemia only). The frequency was also negatively, but weakly, correlated with age and HbA1c (episodes with coma only), but not correlated with sex, duration of diabetes, or patients' ratings of worries about mild and severe hypoglycaemia.

Counterregulatory hormonal response to insulin-induced hypoglycaemia in insulin-dependent diabetic patients: a comparison of equimolar amounts of porcine and semisynthetic human insulin.

The aim of the present study was to compare the degree of hypoglycaemia, the hypoglycaemic symptom score and counterregulatory responses to equimolar amounts of intravenously administered porcine and semisynthetic human insulin in a double-blind crossover study in insulin-dependent diabetic patients. After overnight stabilization of blood glucose to approximately 6 mmol l-1, insulin was infused from 06.00 hours at such a rate as to keep the blood glucose concentration constant at 6 mmol l-1. At 09.00 hours hypoglycaemia was induced by increasing the infusion rate to give a blood glucose level of 2 mmol l-1 within about 60 min. The individual infusion rate from the first test was repeated in the second test, 1 week later. Blood glucose minimum levels were 2.1 (range, 1.3-2.9) and 2.1 (1.3-2.8) mmol l-1 for porcine and human insulin, respectively. The insulin concentrations at blood nadirs were 107 (66-180) and 107 (56-184) pmol l-1, respectively, for porcine compared to human insulin (NS). Symptom scores at minimum blood glucose concentrations were 43 and 46, respectively, with a maximal difference in intensity of 1 point in each patient. There were no statistical differences in the counterregulatory responses of glucagon, epinephrine, norepinephrine, cortisol, growth hormone, prolactin, beta-endorphine or in serum-potassium decreases. Patients were unable to discriminate between the two forms of insulin. It is concluded that there are no differences between porcine and semisynthetic insulin with regard to glucose fall, hormonal counterregulation or symptom scores, when the two forms of insulin are administered intravenously in equimolar amounts.

The relationship between symptomatic and biochemical hypoglycaemia in insulin-dependent diabetic patients.

The relationship between symptomatic (subjective feelings) and biochemical (blood glucose concentration less than 3 mmol l-1) hypoglycaemia was studied in 66 randomly selected insulin-dependent diabetic out-patients under normal conditions of daily life with conventional insulin injection regimens. The patients (a) collected 7-point diurnal blood glucose profiles at home on three consecutive days and then once weekly for 3 weeks, (b) indicated whether they felt hypoglycaemic at sampling times, and (c) collected extra samples if they felt hypoglycaemic at any time during the study period. The weekly frequencies of symptomatic and biochemical hypoglycaemia were 0.99 and 1.75 per patient, respectively. Biochemical hypoglycaemia was present in 29% of the symptomatic episodes, and symptomatic hypoglycaemia accompanied 16% of the biochemical episodes. Symptomatic hypoglycaemia was experienced at a median blood glucose concentration of 3.4 mmol l-1 (range 1.4-14.9 mmol l-1). Fifty per cent of both symptomatic and biochemical episodes occurred before lunch, while the remainder were evenly distributed throughout the day. The occurrence of biochemical hypoglycaemia, but not of symptomatic hypoglycaemia, was inversely correlated with HbA1c and median blood glucose concentration. Thus symptomatic hypoglycaemia is an unreliable indicator of biochemical hypoglycaemia and of the degree of glycaemic control. Blood glucose measurements are a prerequisite for the diagnosis of hypoglycaemia.

[Hypoglycemic effects of equimolar quantities of semisynthetic human and porcine insulin in insulin-dependent diabetic patients]. / Den hypoglykaemiske effekt af aekvimolaere maengder semisyntetisk humant og porcint insulin hos insulinafhaengige diabetiske patienter.

In some diabetic patients, transition from porcine insulin (PI) to human insulin (HI) has resulted in alterations or non-appearance of the usual hypoglycaemic symptoms. The authors have, therefore, undertaken a double-blind cross-over trial with induction of hypoglycaemia with semisynthetic HI and PI administered in equimolar quantities to eight insulin-dependent men. Prior to induction of hypoglycaemia, the blood glucose (BG) was stabilized at approximately 6 mmol/l. At the time 0, the BG was 5.9 (5.4-7.1) mmol/l and 6.2 (4.8-7.1) mmol/l (NS), BS-nadir was 2.1 (1.3-2.9) mmol/l and 2.1 (1.3-2.8) mmol/l PI versus HI. At the time -15 minutes and at BG-nadir, assessment of symptoms and neuropsychological testing were performed. The total symptom scorings were identical for the two types of insulin, the maximum intraindividual difference was +1 on a scale from 0 to 3. Cognitive function was reduced significantly in hypoglycaemia with no differences for the types of insulin. The conclusion is that, in insulin-dependent diabetic patients, no differences in hypoglycaemic effects were observed between PI and HI after intravenous administration of equimolar quantities.

Lens fluorescence in relation to metabolic control of insulin-dependent diabetes mellitus.

The correlation of blue-green lens fluorescence to the metabolic control of insulin-dependent diabetes mellitus was studied in 36 patients in whom the level of glycosylated hemoglobin A1c (HbA1c) had been followed from the onset of diabetes. Good metabolic control (22 patients, all with mean HbA1c levels, less than 7.0% and, thus, low blood glucose concentrations) was associated with less lens fluorescence and a higher lens transmittance than poor metabolic control (14 patients, all with mean HbA1c levels, greater than 9.7%). It appears that in diabetes, an increase in lens fluorescence and a decrease in lens transmittance are delayed by good metabolic control, and that the determination of lens fluorescence provides information about the long-term control of diabetes.

Incidence of nocturnal hypoglycaemia in insulin-dependent diabetic patients on intensive therapy.

The frequency of nocturnal hypoglycaemia, i.e. blood glucose concentration (BG) less than 3.0 mmol/l, was evaluated in consecutively selected insulin-dependent patients on multiple insulin injections (MII), n = 23, or continuous subcutaneous insulin infusions (CSII), n = 25. Blood was sampled hourly from 23.00 to 07.00. Seven patients (30%) on MII had at least one BG less than 3.0 mmol/l during the night. Eleven patients (44%) on CSII had hypoglycaemia (NS). The total number of BGs less than 3.0 mmol/l was higher on CSII, 42 of 225, versus 16 of 207 on MII (p less than 0.025). The duration of hypoglycaemia was 2 hours (range 1-6) on MII and 4 hours (range 1-7) on CSII with a maximal prevalence at 4 hours and between 5 and 7 hours, respectively (p = less than 0.05). The frequency of nocturnal hypoglycaemia is high in patients on intensified insulin regimens. Nocturnal hypoglycaemia occurs later in the night and is of longer duration on CSII than on MII. HbA1c, BG before bedtime and in the morning might be useful in the evaluation of nocturnal hypoglycaemia.

Lens autofluorescence in diabetes compared with the level of glycosylated hemoglobin A1c.

The autofluorescence of the crystalline lens has been measured by an ocular fluorophotometer in two comparable groups of patients with insulin-dependent diabetes mellitus. One group has had a high level of HbA1c since the onset of diabetes (mean 10.1 per cent) and the other group a very low level (mean 6.5 per cent). The group with low HbA1c during the disease period showed a significantly lower lens fluorescence than the group with high HbA1c.

Nocturnal hypoglycaemia in patients receiving conventional treatment with insulin.

The prevalence of nocturnal biochemical hypoglycaemia--that is, blood glucose concentrations below 3 mmol/l (55 mg/100 ml)--was evaluated in a random sample of 58 insulin dependent diabetics receiving twice daily insulin. Seventeen patients had at least one blood glucose value below 3 mmol/l (55 mg/100 ml) and five a value below 2 mmol/l (36 mg/100 ml) during the night. Both bedtime (2300) and fasting morning (0700) blood glucose concentrations were significantly lower in the group with nocturnal hypoglycaemia compared with the group without (p less than 0.00001). If the bedtime blood glucose concentration was below 6 mmol/l (108 mg/100 ml) the risk of nocturnal hypoglycaemia was 80% (95% confidence limits 51-96%). If the bedtime blood glucose concentration was above 6 mmol/l the likelihood of hypoglycaemia not occurring during the night was 88% (74-96%). The mean glycosylated haemoglobin A1c (HbA1c) concentration in the group with nocturnal biochemical hypoglycaemia (8.2 (range 5.0-12.4)%) was significantly lower than that in the group without (9.4(7.0-14.2)%) (p less than 0.02). The prevalence of nocturnal hypoglycaemia in the patients receiving twice daily insulin (29%) was compared with that in 15 patients receiving thrice daily insulin (47%) and was not found to be significantly different. The likelihood of this risk being greater with thrice daily insulin was, however, 88%. No patient with nocturnal biochemical hypoglycaemia woke up during the night with symptomatic hypoglycaemia. Nocturnal biochemical hypoglycaemia is common during twice daily treatment with insulin, and low values of HbA1c might be associated with a higher risk of such hypoglycaemia. The blood glucose concentration at bedtime is a significant predictor of nocturnal biochemical hypoglycaemia, and HbA1c values might be of help in identifying patients at risk.