Causes of death in children with insulin dependent diabetes 1990-96.
(41/2319)
BACKGROUND: Mortality rates in children with insulin dependent diabetes (IDDM) in the UK are unknown and the causes of death not well documented. AIM: To determine the mortality rate and causes of death in children with IDDM. METHODS: The Office of National Statistics (England and Wales) and the General Register Office (Scotland) notified all deaths under 20 years of age from 1990 to 1996 with diabetes on the certificate. Further details were provided by coroners, pathologists, and clinicians. RESULTS: 116 deaths were notified and 83 were caused by diabetes. The standardised mortality ratio was 2.3 (95% confidence interval (CI), 1.9 to 2.9), being highest in the age group 1-4 years, at 9.2 (95% CI, 5.4 to 14.7). Of the 83 diabetic deaths, hyperglycaemia/diabetic ketoacidosis (DKA) was implicated in 69 and hypoglycaemia in 7. Cerebral oedema was the most common cause of death in young children (25 of 36 diabetes related deaths in children under 12 years of age). 34 young people (10-19 years; 24 male) were either found dead at home (n = 26) or moribund on arrival at hospital (n = 8). In 24 of these, it appeared that DKA was the cause of death, in four hypoglycaemia was likely. Nine of these were found "dead in bed". CONCLUSIONS: Children with IDDM have a higher mortality than the general population. Cerebral oedema accounts for most hospital deaths in young children. There are a large number of young men dying at home from neglected IDDM. Early diagnosis of IDDM in children and closer supervision of young people might prevent some of these deaths. (+info)
Cognitive function and mood after profound nocturnal hypoglycaemia in prepubertal children with conventional insulin treatment for diabetes.
(42/2319)
OBJECTIVES: To examine the frequency of nocturnal hypoglycaemia, and the effects on cognitive function and mood, in children with insulin dependent diabetes mellitus (IDDM). DESIGN: Two overnight glucose profiles, in the home environment, and assessments of cognitive function and mood the following day. Twenty nine prepubertal patients with IDDM (median age, 9.4 years; range, 5.3-12.9) and 15 healthy controls (single overnight profile), median age 9.5 (range, 5.6-12.1) years were studied. RESULTS: Asymptomatic hypoglycaemia (glucose < 3.5 mmol/l) was observed in 13 of 29 patients studied on night 1: four of these and seven others were hypoglycaemic on night 2. The median glucose nadir was 1.9 (range, 1.1-3.3) mmol/l and the median duration of hypoglycaemia was 270 (range, 30-630) minutes. Hypoglycaemia was related to insulin dose, but not glycosylated haemoglobin (HbA1c) values, and was partially predicted by a midnight glucose of < 7.2 mmol/l. Cognitive performance was not altered after hypoglycaemia but a lowering of mood was observed. CONCLUSIONS: Young children on conventional insulin regimens are at high risk for profound, asymptomatic nocturnal hypoglycaemia, which is difficult to predict. There was no short term effect on cognitive function but mood change was detected. (+info)
Combined mechanical trauma and metabolic impairment in vitro induces NMDA receptor-dependent neuronal cell death and caspase-3-dependent apoptosis.
(43/2319)
Neuronal necrosis and apoptosis occur after traumatic brain injury (TBI) in animals and contribute to subsequent neurological deficits. In contrast, relatively little apoptosis is found after mechanical injury in vitro. Because in vivo trauma models and clinical head injury have associated cerebral ischemia and/or metabolic impairment, we transiently impaired cellular metabolism after mechanical trauma of neuronal-glial cultures by combining 3-nitropropionic acid treatment with concurrent glucose deprivation. This produced greater neuronal cell death than mechanical trauma alone. Such injury was attenuated by the NMDA receptor antagonist dizocilpine (MK801). In addition, this injury significantly increased the number of apoptotic cells over that accruing from mechanical injury alone. This apoptotic cell death was accompanied by DNA fragmentation, attenuated by cycloheximide, and associated with an increase in caspase-3-like but not caspase-1-like activity. Cell death was reduced by the pan-caspase inhibitor BAF or the caspase-3 selective inhibitor z-DEVD-fmk, whereas the caspase-1 selective inhibitor z-YVAD-fmk had no effect; z-DEVD-fmk also reduced the number of apoptotic cells after combined injury. Moreover, cotreatment with MK801 and BAF resulted in greater neuroprotection than either drug alone. Thus, in vitro trauma with concurrent metabolic inhibition parallels in vivo TBI, showing both NMDA-sensitive necrosis and caspase-3-dependent apoptosis. (+info)
Rapid monitoring of diffusion, DC potential, and blood oxygenation changes during global ischemia. Effects of hypoglycemia, hyperglycemia, and TTX.
(44/2319)
BACKGROUND AND PURPOSE: The increasing interest in diffusion-weighted MRI (MRI) for diagnosis and monitoring of acute stroke in humans calls for a sound understanding of the underlying mechanisms of this image contrast in acute cerebral ischemia. The present study aimed to show that a rapid decrease in brain-water apparent diffusion coefficient (ADC) occurs coincident with anoxic depolarization and that this change is delayed by hyperglycemia and sodium channel blockade but accelerated by hypoglycemia. METHODS: Rats were divided into groups: normoglycemic, hypoglycemic, and hyperglycemic, and those given local tetrodotoxin (TTX) application. Cardiac arrest was effected by intravenous KCl injection during serial high-speed diffusion and blood oxygenation-sensitive gradient-recalled echo MRI. Brain DC potential was recorded simultaneously. Serial ADC maps were calculated from the diffusion-weighted data and fitted to a model function to measure the delay between cardiac arrest and rapid ADC decrease. RESULTS: The time of anoxic depolarization indicated by DC change agreed well with the rapid drop in ADC in all groups; both were accelerated with hypoglycemia and delayed by hyperglycemia. A more gradual ADC decline occurred before anoxic depolarization, which was more pronounced in hyperglycemic animals and less pronounced in hypoglycemic animals. Rapid drop in ADC was also delayed by local TTX application. Changes in gradient-recalled echo image intensity were not significantly different among groups. CONCLUSIONS: While much of the ADC decrease in ischemia occurs during anoxic depolarization, significant but gradual ADC changes occur earlier that may not be due to a massive loss in ion homeostasis. (+info)
Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. U.K. Lispro Study Group.
(45/2319)
OBJECTIVE: To measure the effectiveness of insulin lispro, a fast-acting insulin analog, in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy. RESEARCH DESIGN AND METHODS: In 11 diabetes outpatient clinics in the U.K., 165 subjects with type 1 diabetes were enrolled in a randomized crossover open-label study with a 2-month run-in period and then treated with a basal bolus regimen. Patients used human NPH insulin at night with either premeal insulin lispro for 4 months followed by human regular insulin for another 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months. The main outcome measures were the number of hypoglycemic episodes during both treatments and HbA1c level. RESULTS: A total of 135 patients were randomized, with 68 receiving insulin lispro and 67 receiving human regular insulin for the first 4 months. The data for the first 4 months of treatment only were compared as two independent groups because of a period effect and a treatment-period interaction. Glycemic control was equally tight during treatment with human regular insulin (HbA1c, 6.2 +/- 0.8%) and insulin lispro (6.0 +/- 0.9%). A total of 1,156 hypoglycemic episodes occurred during treatment with human regular insulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro (P = 0.04). This difference was chiefly because of a reduced number of nocturnal episodes (181 vs. 52, P = 0.001) in the insulin lispro group. CONCLUSIONS: The use of a fast-acting insulin analog, insulin lispro, as part of a basal bolus regimen reduces nocturnal hypoglycemia in patients with type 1 diabetes who maintain tight glycemic control during intensive insulin therapy. (+info)
Hypothalamic orexin expression: modulation by blood glucose and feeding.
(46/2319)
Orexins (hypocretins), novel peptides expressed in specific neurons of the lateral hypothalamic area (LHA), stimulate feeding when injected intracerebroventricularly. We investigated their role in feeding in the rat by measuring hypothalamic prepro-orexin mRNA levels under contrasting conditions of increased hunger. Prepro-orexin mRNA levels increased significantly after 48 h of fasting (by 90-170%; P < 0.05) and after acute (6 h) hypoglycemia when food was withheld (by 90%; P < 0.02). By contrast, levels were unchanged during chronic food restriction, streptozotocin-induced diabetes, hypoglycemia when food was available, voluntary overconsumption of palatable food, or glucoprivation induced by systemic 2-deoxy-D-glucose. Orexin expression was not obviously related to changes in body weight, insulin, or leptin, but was stimulated under conditions of low plasma glucose in the absence of food. Orexins may participate in the short-term regulation of energy homeostasis by initiating feeding in response to falls in glucose and terminating it after food ingestion. The LHA is known to contain neurons that are stimulated by falls in circulating glucose but inhibited by feeding-related signals from the viscera; orexin neurons may correspond to this neuronal population. (+info)
Channelopathies of inwardly rectifying potassium channels.
(47/2319)
Mutations in genes encoding ion channels have increasingly been identified to cause disease conditions collectively termed channelopathies. Recognizing the molecular basis of an ion channel disease has provided new opportunities for screening, early diagnosis, and therapy of such conditions. This synopsis provides an overview of progress in the identification of molecular defects in inwardly rectifying potassium (Kir) channels. Structurally and functionally distinct from other channel families, Kir channels are ubiquitously expressed and serve functions as diverse as regulation of resting membrane potential, maintenance of K(+) homeostasis, control of heart rate, and hormone secretion. In humans, persistent hyperinsulinemic hypoglycemia of infancy, a disorder affecting the function of pancreatic beta cells, and Bartter's syndrome, characterized by hypokalemic alkalosis, hypercalciuria, increased serum aldosterone, and plasma renin activity, are the two major diseases linked so far to mutations in a Kir channel or associated protein. In addition, the weaver phenotype, a neurological disorder in mice, has also been associated with mutations in a Kir channel subtype. Further genetic linkage analysis and full understanding of the consequence that a defect in a Kir channel would have on disease pathogenesis are among the priorities in this emerging field of molecular medicine. (+info)
Continuous subcutaneous insulin infusion. A new way to lower risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes.
(48/2319)
OBJECTIVE: Recommendations from the Diabetes Control and Complications Trial (DCCT) indicate that adolescents with type 1 diabetes should be treated with intensive therapy involving multiple daily injections (MDI) of insulin or insulin pump therapy (continuous subcutaneous insulin infusion [CSII] to help obtain better metabolic control and prevent later complications. Interest has thus focused on insulin pump therapy to help adolescents meet this challenge. The purpose of this study was to examine responses to CSII and MDI in a large group of adolescents with established type 1 diabetes during a 12-month period and to determine whether either treatment regimen more favorably affected clinical and psychosocial outcomes. RESEARCH DESIGN AND METHODS: One-third of 75 youths aged 12-20 years who were candidates for intensive therapy chose CSII as their mode of treatment. Patients received intensive treatment and education as described by the DCCT investigators. Psychosocial data (e.g., quality of life, depression, self-efficacy, and coping) were collected at baseline and at 6-month intervals, and clinical data (e.g., HbA1c levels, adverse events) were collected every 4-6 weeks. RESULTS: Although both MDI- and CSII-treated adolescents initially exhibited improved metabolic control, this level of control was more difficult to sustain for 12 months in the MDI group (at 6 months HbA1c = 8.1, at 12 months HbA1c = 8.3), whereas average HbA1c levels in the CSII group continued to decrease during the 12 months of treatment (at 6 months HbA1c = 7.7, at 12 months HbA1c = 7.5). Despite lower HbA1c levels in CSII-versus MDI-treated patients, the rate of severe hypoglycemic events was reduced by almost 50% in the CSII group (P = 0.01). Self-reported questionnaires demonstrated that there was improvement in self-efficacy, depression, and quality of life in both MDI- and CSII-treated patients. Finally, adolescents using CSII found coping with diabetes to be less difficult than adolescents using MDI did. CONCLUSIONS: CSII is an alternative means to lower HbA1c levels and reduce the risk of hypoglycemia without adversely affecting psychosocial outcomes in adolescents with type 1 diabetes. (+info)