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PubMed1987

Predicting nocturnal hypoglycemia in patients with type I diabetes treated with continuous subcutaneous insulin infusion.

The incidence of low nocturnal blood glucose values (i.e., less than 65 mg/dl) was assessed in 20 insulin-dependent diabetic patients treated with continuous subcutaneous insulin infusion supported by capillary blood glucose monitoring before each meal and the evening snack. Patients were randomly assigned to a control or experimental group. Both groups followed an identical protocol for the first part of the study (baseline). Patients were instructed to determine capillary blood glucose measurements five times during the night for three consecutive nights. The same procedure was repeated one week later, but this time the subjects in the experimental group were instructed to have an extra snack if capillary blood glucose levels at 10:30 P.M. were 120 mg/dl or less. The control group continued with the usual routine of one evening snack at 9 P.M. At baseline, the incidence of capillary blood glucose values of less than 65 mg/dl was 13 percent. The ingestion of an extra snack at bedtime resulted in the absence of capillary blood glucose values of less than 65 mg/dl in the experimental group, whereas the incidence of capillary blood glucose values of less than 65 mg/dl in the control group remained 13 percent (p = 0.038). The capillary blood glucose concentration at 10:30 P.M. was highly predictive of the risk of nocturnal blood glucose values below 65 mg/dl (p = 0.015) and fasting capillary blood glucose values above 140 mg/dl (p = 0.0001). These data show that nocturnal hypoglycemia may be a considerable problem during continuous subcutaneous insulin infusion therapy even if the basal infusion rate is adjusted in the hospital on the basis of nocturnal blood glucose concentrations. The ingestion of an extra snack at bedtime for capillary blood glucose values below 120 mg/dl has the potential to minimize this risk. The capillary blood glucose concentration at 10:30 P.M. is a significant predictor of nocturnal hypoglycemia.

Adolescent↗
PubMed1999

Is glycosuria a reliable indicator of adequacy of glucose infusion rate in preterm infants?

CONTEXT: Adequacy of glucose infusion may be monitored via the glycosuria levels, as there is a relationship between glycemia and glycosuria regulated by the renal glucose threshold. In the neonatal period, however, this relationship is not so clear. OBJECTIVE: To evaluate the occurrence of glycosuria in preferm infants submitted to glucose infusion and to verify the relationship between glycosuria and blood glucose level. DESIGN: Accuracy study. SETTING: Neonatal intensive care unit of General Maternity Hospital. PATIENTS: 40 Preterm newborns receiving glucose infusion. PROCEDURES: 511 concomitant determinations of glycemia and glycosuria were performed. These 511 pairs were divided into stable and unstable, according to the clinical status of the newborn at the time of data collection, and they were studied in relation to the gestational age, birth weight and glucose infusion rate. RESULTS: The results revealed a greater frequency of glycosuria in gestational age < or = 30 weeks, birth weight < 1500 g and glucose infusion rate > 6 mg/kg/min. Eight (25.8%) episodes of positive glycosuria occurred in the absence of hyperglycemia, indicating only a moderate concordance between them. CONCLUSION: Glycosuria alone is an unreliable marker of blood glucose concentration and adequacy of glucose infusion rate. It is therefore necessary to monitor blood glucose levels in infants submitted to continuous glucose infusion.

Biomarkers↗
PubMed2001

Intensive insulin treatment in diabetic children.

Intensification of insulin therapy which maintains long-term near-normoglycaemia (HbA1c<7.0%) strongly protects against onset and/or progression of diabetic microangiopathy in Type 1 diabetes mellitus of adults. Similar intensification of insulin therapy is needed in diabetic children as well, in order to prevent complications a few years after diabetes onset, ie very often in young age. Provided adequate psychosocial support and education are available, children should be treated with multiple daily injections of insulin or, when necessary, with continuous subcutaneous insulin infusion, along with blood glucose monitoring. Insulin regimens may differ from child to child and vary from day to day in the same child, depending on lifestyle and considering all the available insulin preparations. These include the short-acting insulin (both human regular and short-acting insulin analogues), the intermediate-acting insulin (NPH and Lente), as well as the new long-acting insulin analogue glargine. The latter seems a promising candidate to substitute of basal insulin. The concern that intensified insulin therapy increases the risk of hypoglycaemia, as indicated by the Diabetes Control and Complications Trial (DCCT), is no longer tenable. On the contrary, a physiological, flexible insulin regimen better than a fixed insulin regimen, usually the twice daily split-mixed regimen, protects against the risk of hypoglycaemia in relation to food ingestion, physical exercise and sleep. Thus, appropriate education should be delivered at diabetes onset to the child and parents in order to start the strategy of intensified insulin therapy as early as possible.

Blood Glucose↗
PubMed1980

Use of an extracorporeal glucose monitor for the diagnosis and surgical treatment of an insulinoma.

An extracorporeal glucose monitor (EGM) has been used in a patient with an insulinoma. This system, which continuously measures blood glucose, can be used in combination with a feedback-controlled glucose infusion to maintain glycaemia at any preselected level. It prevents the risk of severe hypoglycaemia during diagnostic tests (total fast, tolbutamide and insulin tolerance tests) as well as during surgery. It also helps in determining whether all the insulin-secreting tumour tissue has been removed. The EGM is thus helpful in the diagnosis and surgical treatment of insulinomas.

Adenoma, Islet Cell↗
PubMed1999

Monitoring by subcutaneous microdialysis in neurosurgical intensive care.

Microdialysis is an in vivo sampling technique which provides a powerful approach to monitoring metabolic events. We have performed a study to determine the feasibility and effectiveness of subcutaneous microdialysis in monitoring patients on the Neurosurgical Intensive Care Unit (NICU). A microdialysis probe was placed in the subcutaneous fat of the anterior abdominal wall and perfused with Ringer's solution. Collecting vials were changed every 30 minutes and monitoring continued for 2-6 days. Biochemical analysis of glucose, lactate, and glutamate was correlated with clinical events. The normal ranges of glucose, lactate and glutamate were 3-6 mM. 1-2.5 mM and 5-20 microM, respectively. Periods of low tissue glucose were detected by microdialysis which were not detected by routine plasma sampling. In one patient, following an apparently brief period of hypoxia, there was a prolonged disturbance of tissue chemistry. Another patient with obesity had significantly higher concentrations of dialysate glucose, lactate and glutamate. Monitoring by subcutaneous microdialysis on intensive care units is feasible, reveals unexpected changes in tissue metabolism and might be an important adjunct for the interpretation of intracerebral data.

Adolescent↗
PubMed1986

Metabolic effects of glucagon in endotoxemic minipigs.

A treatment group of four 50-80-kg Yucatan minipigs was fitted with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate transhepatic kinetics of glucose, lactate, and insulin. Three days later, they were placed in slings, and a primed-continuous intravenous infusion of 3-tritiated glucose was initiated to monitor whole body glucose kinetics. Following a 3-hour control period, an intravenous infusion of E. coli endotoxin was administered at 15 micrograms/kg/hr for 6 hours. After 1 hour of endotoxin infusion, glucagon was administered as a primed (50 micrograms/kg)-continuous (50 micrograms/kg/hr) intravenous infusion for 5 hours. These results were compared statistically to a control group of eight minipigs given endotoxin only. Glucagon caused a transient (less than 1 hour) peak elevation of arterial glucose levels due to increased hepatic glycogenolysis immediately following initiation of the glucagon infusion. Despite enhanced extrahepatic (renal) gluconeogenesis, plasma glucose concentrations decreased to the hypoglycemic levels of the control group, as glucagon was unable to overcome the relative endotoxic inhibition of hepatic gluconeogenesis. Pancreatic output of insulin increased sixfold resulting in threefold increments in transhepatic uptake and arterial serum insulin levels. Arterial lactate and pyruvate concentrations were elevated due to increased peripheral production and hepatic output. Survivability in the treatment group (75%) improved over the control group (33%).

Animals↗
PubMed1986

Metabolic effects of sodium dichloroacetate in endotoxemic minipigs.

Lactic acidosis is significant in the pathophysiology of endotoxicosis. By increasing the activity of pyruvate dehydrogenase, sodium dichloroacetate (DCA) decreases lactate production and may be useful as a therapy for endotoxic shock. Five (n = 5) 50-80-kg Yucatan minipigs were fitted with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate transhepatic kinetics of glucose, lactate, and insulin. Three days later, they were placed in slings, and a primed-continuous intravenous infusion of 3-tritiated glucose was initiated to monitor whole body glucose kinetics. Following a 3-hour control period, an intravenous infusion of E. coli endotoxin (LPS) was administered at 15 micrograms/kg/hr for 6 hours. After 1 hour of LPS infusion, DCA was administered as a primed (30 mg/kg)-continuous (30 mg/kg/hr) intravenous infusion for 5 hours. These DCA-treated endotoxemic minipigs (group DE) were compared statistically to a group (n = 8) of minipigs given endotoxin only (group E). Group DE arterial lactate concentrations eventually decreased (19.2 +/- 1.0 mg/dl) significantly (P less than or equal to 0.05) below group E (39.3 +/- 7.7 mg/dl) in the last hour of DCA infusion. The progressive hypoglycemia of group DE decreased below that of group E and became significantly (P less than or equal to 0.05) lower in the last hour of the experiment (33.6 +/- 11.5 vs 50.6 +/- 10.0 mg/dl, respectively) due to decreased hepatic gluconeogenesis as evidenced by a lower relative rate of appearance (%Ra) of glucose and decreased hepatic glucose output and lactate extraction. A large relative decrease in pancreatic output of insulin in group DE contributed to the lower serum insulin levels than group E throughout the treatment period. Lethality in group DE (60%) was unaltered from that of group E (67%). Despite its ability to decrease arterial lactate concentrations, DCA alone does not appear to be an effective treatment for endotoxicosis.

Acetates↗
PubMed1986

Carbohydrate-induced thermogenesis in man.

The effect of thermogenesis due to carbohydrate depends upon the metabolic utilisation of the nutrient. With the glucose clamp technique, when infusing glucose and insulin simultaneously, one can study glucose metabolism under steady states glucose and insulin plasma levels. The amount of glucose needed to maintain euglycemia can be monitored. The increment of energy expenditure is continuously measured by open circuit indirect calorimetry. The combined technique of glucose clamp with continuous indirect calorimetry allows to determine the rate of glucose storage. The experimental value for glucose-induced thermogenesis measured over three hours following glucose ingestion in young adults is around 12 to 15% of the energy content of the glucose load. The results support the concept of two components in the thermogenic response to glucose infusion: an "obligatory thermogenesis" which accounts for the energy costs of storing the nutrient and a "facultative thermogenesis" which is an energy dissipative process.

Adult↗
PubMed2001

Glucose monitoring with long-term subcutaneous microdialysis in neonates.

BACKGROUND: Microdialysis is a new approach for continuous monitoring of small molecules in the extracellular space, and hypoglycemia is a common problem in neonatal intensive care. The objective of this study was to evaluate subcutaneous microdialysis for long-term glucose monitoring in neonatal intensive care. We determined the relative recovery of the microdialysis system in vitro and in vivo, the stability of the relative recovery in vivo during long-term microdialysis, and the correlation between blood and dialysate concentrations of glucose and urea. Furthermore, we evaluated the sensitivity and specificy of subcutaneous microdialysis for the diagnosis of hypoglycemia. PATIENT AND METHODS: Thirteen infants (10 neonates) with gestational ages of 30.2 to 45.6 weeks were investigated by microdialysis of subcutaneous adipose tissue and blood sampling. Subcutaneous microdialysis was performed for a median (range) duration of 9 (4-16) days. RESULTS: The application was safe, even in extremely low birth weight infants (<1000 g) with scanty subcutaneous adipose tissue. The mean +/- standard deviation of the relative recovery in vitro was 101 +/- 3% for glucose and 100 +/- 2% for urea. Using urea as the internal standard, the mean relative recovery in vivo was 96.4 +/- 12.7% at the beginning and remained constant up to 16 days. The correlation between microdialysate and blood was significant for glucose (r = 0.88) and urea (r = 0.98). Subcutaneous microdialysis allowed the detection of asymptomatic hypoglycemias. The diagnostic sensitivity of a dialysate glucose </=2.9 mM to predict a blood glucose level </=2.8 mM was 92.3%, with 88.1% specificy. The positive predictive value with a 13.4% prevalence of a blood glucose </=2.8 mM was 54.5%, with a negative predictive value of 98.7% and an accuracy of 88.7%. CONCLUSIONS: Subcutaneous microdialysis is a safe method, well suited for long-term glucose monitoring in neonates during intensive care. Subcutaneous microdialysis can be used to reduce blood loss and painful stress resulting from diagnostic blood sampling in high-risk neonates.

Blood Glucose↗
PubMed1991

Hypothermia is critical for survival during prolonged insulin-induced hypoglycemia in rats.

Hypothermia is a well-known concomitant of hypoglycemia in mammals. We tested the hypothesis that this hypothermia is an important adaptive response to hypoglycemia in 11 normal Sprague-Dawley rats. Twelve-hour fasted, conscious animals received primed, continuous insulin infusions for up to 8 hours. Plasma glucose was clamped between 30 and 40 mg/dL and core body temperature was monitored continuously during the insulin infusions. Five of the animals were maintained in a room temperature environment (22 to 24 degrees C) during the hypoglycemia; all became hypothermic (mean +/- SE nadir core temperature, 31 +/- 0.5 degrees C). Spontaneous activity was reduced in these animals, but they remained conscious and responsive to external stimuli. All five returned to normal behavior after euglycemia was restored at the end of the insulin infusions. In the remaining six animals, hypothermia was prevented during hypoglycemia by warming of the air in their cages (mean of hourly core temperatures, 37 +/- 0.1 degrees C). None of these animals survived more than 7 hours. The severity of the hypoglycemia was no greater in the euthermic than in the hypothermic group, as judged by the mean of individual nadir plasma glucose levels (25 +/- 1 v 24 +/- 1 mg/dl, respectively) and by the mean number of glucose values per animal that were less than 30 mg/dL (2 +/- 1 v 7 +/- 1). Plasma osmolality did not change significantly in either group during the period of hypoglycemia, suggesting that dehydration was not the cause of death in the euthermic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMedDate not supplied

[Lack of benefit from the intermittent administration of insulin in treatment using subcutaneous perfusion pump in type 1 diabetes].

Our study is based on two constatations: 1) Hyperinsulinaemia, a possible atherogenic factor, is frequent under continuous subcutaneous insulin infusion. 2) Pulsatile intravenous insulin delivery improve the insulin's hypoglycaemic activity. To test if equivalent metabolic control can be obtained with a reduced intermittent subcutaneous infused insulin dose, we compared nocturnal metabolic control of 8 c-peptide negative type 1 diabetic patients under three experimental conditions: Continuous usual dose test (1.0 +/- 0.1 u/h); Intermittent half dose test (1.0 +/- 0.1 u/h, 30 min/h); Continuous half dose test (0.5 +/- 0.05 u/h) Five parameters were monitored: blood glucose, plasma free insulin and beta-hydroxy-butyrate, free fatty acid and glycerol plasma level. No significant differences were found between intermittent and continuous half-dose tests. We conclude that, in our experimental conditions, intermittent subcutaneous insulin infusion does not reduce the metabolic degradation induced by insulin dose reduction.

3-Hydroxybutyric Acid↗
PubMed1983

Feasibility of strict diabetes control in insulin-dependent diabetic adolescents.

Nineteen insulin-dependent diabetic adolescents who had poor control on twice daily injections and home glucose monitoring participated in a study assessing the feasibility of improved control. Using a randomized crossover protocol, we examined the relative efficacy of continuous subcutaneous insulin infusion and of intensive conventional therapy with three or four daily injections of insulin. Both therapies were regulated with home glucose monitoring. A marked improvement in control with both therapies was observed when mean blood glucose and glycosylated hemoglobin A1 were compared with conventional therapy. However, pump therapy resulted in significantly lower HbA1 than intensive therapy (P less than 0.05), despite a significantly lower total insulin dose (P less than 0.01). We conclude that in adolescents with type I diabetes, continuous subcutaneous insulin infusion is more effective in achieving improvement of diabetes control than is intensive conventional therapy in the outpatient setting.

Adolescent↗
PubMed1994

Understanding the dynamics of cellular responsiveness to modifications of metabolic substrates in perifusion.

A novel microperifusion system with capabilities for continuous, real-time, potentiometric monitoring of extracellular hydrogen ion concentration has been used to define the response of HeLa cells to abrupt changes in extracellular energy sources or introduction of an inhibitor of glycolysis. Glycolytic inhibition, induced by removal of glucose or introduction of iodoacetate, each led to a rapid, continuous decrease in acid release. The response to iodoacetate took longer than removal of glucose, perhaps due to the time required for binding and activation. Once inhibition began, however, the rate of change was greater than following glucose removal. Conversely, recovery time following iodoacetate inhibition was much slower than with glucose removal. Unlike the response to short-term glucose depletion, a second pulse of iodoacetate resulted in a faster response followed by an even longer recovery time. The response to switching between glucose and glutamine began almost without evident delay. The response patterns revealed that HeLa cells prefer glutamine to glucose, but, in the presence of both energy sources, some glucose continues to be used. In summary, these results indicate that continuous, real-time monitoring of the kinetics of hydrogen-ion release can be used to gain new insights into the dynamics of cellular response to perturbations of extracellular energy sources.

Energy Metabolism↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed1984

Reaction rate studies of glucose-6-phosphate dehydrogenase in rat tracheal epithelium; the effect of section thickness.

The reaction velocity of glucose-6-phosphate dehydrogenase has been quantified by continuous monitoring on a Vickers microdensitometer of the reaction product as it formed in sections of different thickness of rat tracheal epithelium. Reaction velocity was directly proportional to section thickness when either tetranitro BT or neotetrazolium was used as the final acceptor; the rate was the same with each tetrazolium salt. However, the amount of formazan deposited in a given time was not proportional to section thickness. When tetranitro BT was employed the reaction became non-linear in the thicker sections due to the inability of the instrument to record beyond a certain absorbance value. Using neotetrazolium a lag phase, due to the failure to overcome the critical supersaturation level of the formazan, preceded the linear response. The duration of this phase decreased as section thickness increased. The implications of these findings on studies using conventional "end point" methods of measurement are discussed.

Animals↗