Prolonged bilateral reactive miosis as a symptom of severe insulin intoxication.

BACKGROUND: Miosis occurs following exposure to toxins that decrease the sympathomimetic tone, increase the cholinergic tone, or exert sedative-hypnotic effects, but has not been reported in insulin poisoning. CASE REPORT: A 64-year- old woman without co-morbidities was found unconscious next to an empty insulin pen. Her Glasgow Coma Scale was 3 with absent reflexes, bilateral reactive miosis, and injection marks across the abdominal wall. The patient was endotracheally intubated, mechanically ventilated, and transferred to this hospital. At admission, the blood glucose level was 34 mg/dL. Glasgow Coma Scale remained at 3, with persistent bilateral reactive miosis. The toxicology screening was negative for ethanol, barbiturates, tricyclic antidepressants, phenothiazines, amphetamines, cannabinoids, salicylates, acetaminophen, and cocaine. Cranial computed tomography with angiography and magnetic resonance imaging (MRI) did not show any structural brain lesions. Intravenous glucose was continued at 6-14 g/h for 3 days. On repeated neurological examinations, the patient remained deeply comatose, with partial loss of cranial nerve function. Bilateral reactive miosis persisted for 4 days. From day 5 on, the patient awoke progressively. At discharge, the patient was fully alert and orientated, without a focal neurological deficit. CONCLUSIONS: Prolonged bilateral reactive miosis can be a clinical symptom accompanying metabolic encephalopathy in severe insulin poisoning. Functional impairment of the pons due to relative hypoperfusion during hypoglycemia may serve as a reasonable pathophysiologic explanation for this phenomenon.

[Potential impact of carbohydrate and fat intake on cardiac hypertrophy]. / Udzial weglowodanów i tluszczów zawartych w diecie w rozwoju przerostu serca.

Currently, a high carbohydrate/low fat diet is recommended for patients with heart failure and/or hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate might play in the development of LVH and heart failure has not been well characterized. Recent studies demonstrate that cardiomyocyte hypertrophy can also be triggered by activation of insulin signalling pathways, altered adipokine levels or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH and heart failure. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy. PPARs also activate cardiac gene expression and growth, and are stimulated by fatty acids and consumption of a high fat diet. Dietary intake of fats and carbohydrate, the resultant effects of plasma insulin, adipokine, and lipid concentrations, may affect cardiomyocyte size and function, particularly following cardiac injury or with chronic hypertension. This review discusses potential mechanisms by which dietary carbohydrates and fats can affect cardiac growth, metabolism and function, particularly in the context of pressure overload LVH.

Cognitive functioning in children with early onset type 1 diabetes and severe hypoglycemia.

OBJECTIVE: To investigate whether severe hypoglycemia in young children with early-onset type 1 diabetes (T1DM) is associated with subsequent abnormalities in cognitive status. STUDY DESIGN: Recruitment was from a large population-based database of children and adolescents with T1DM. Children and adolescents with early-onset T1DM (<6 years) were eligible for the study. Diabetic individuals (n = 41) with a prospectively documented history of seizure or coma were compared with peers with no history of severe hypoglycemic events (n = 43). A comprehensive test battery of learning and memory was used together with intellectual and behavioral measures. RESULTS: No significant group differences were revealed on the intellectual, memory, or behavioral measures. Similarly, those participants with a history of early first seizure did not differ from their peers with no seizures. There were no significant group differences on the memory subtests that were examined given their potential sensitivity to compromised hippocampal function. CONCLUSIONS: There was no clear evidence from this cohort that episodes of seizure or coma, even those occurring in very early childhood, resulted in broad cognitive dysfunction, nor was there evidence of specific memory difficulties at the time of testing in children and adolescents with early-onset T1DM.

A case report of warm weather accidental hypothermia.

A case of hypothermia is presented as a reminder to "Deep South" physicians that our warm weather is not prophylaxis against this syndrome; and many common situations, diseases and medications contribute to and worsen the condition. Diagnosis is made by obtaining a true core body temperature and effective treatment modalities can be easily applied. With appropriate rewarming, a search for complications and monitoring of patient progress a gratifying outcome should result for both patient and physician.

Reversible amnesia in a Type 1 diabetic patient and bilateral hippocampal lesions on magnetic resonance imaging (MRI).

AIMS: Intensive insulin therapy of Type 1 diabetes limits its chronic complications, but is associated with an increased risk of severe hypoglycaemia and its neuroglycopenic consequences. METHODS: Case report. RESULTS: A 24-year-old male with 15 years' history of Type 1 diabetes, who was missing for 48 h, was found at home in ketoacidosis coma. Intensive care permitted a rapid improvement revealing an unexpected severe anterograde amnesia, confirmed by neuropsychological testing. MRI performed 4 days after admission showed abnormal bilateral hyperintensity signals on T2-weighted images in the hippocampus. Three months later, the patient had nearly completely recovered and resumed work. MR images and neuropsychological testing returned to normal. CONCLUSIONS: The most likely course of events favours an initial prolonged hypoglycaemic coma following insulin overdose. The hippocampal injury may be a result of hypoglycaemia. Neuropsychological testing and MRI abnormalities were completely reversible. This case underlines the potential risks of intensive insulin therapy.

Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia.

Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg.kg-1 i.p., followed by an i.v. infusion of 225 micrograms.kg-1.min-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg.kg-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg.kg-1 i.p., followed by an i.v. infusion of 225 micrograms.kg-1.min-1 for 6 h), with dizocilpine 0.33 mg.kg-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40,116 [D-(E)-2-amino-4-methyl-5-phosphono-3- pentenoic acid] 10 mg.kg-1 given i.p. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

[ATPase activity of rat brain microsomal and synaptosomal fractions in insulin hypoglycemia and its treatment with glucose]. / ATFaznaia aktivnost' mikrosomal'noi i sinaptosomal'noi fraktsii otdelov mozga krys pri insulinovoi gipoglikemii i ee kupirovanii gliukozoi.

Experiments on albino rats were made to investigate the activity of Na+, K(+)-ATPase and Mg(2+)-ATPase of fractions of microsomes and nerve endings, isolated from the cortex of the cerebral hemispheres, subcortical structures and medulla oblongata. The brain of healthy animals and that of rats in the state of insulin coma (40 units/kg of the hormone intramuscularly) were investigated at various periods after coma arrest with glucose. It has been assumed that an increase in the number of active molecules of Na+, K(+)-ATPase under the influence of structural changes of membranes in hypoglycemia cannot provide the electric activity of neurons in the absence of glycolytic ATP in neuroglycopenia.

Reversible decerebrate posturing after profound and prolonged hypoglycemia.

Decerebrate rigidity is one of several reversible neurological abnormalities which have been observed in the setting of metabolic coma. We present the case of a patient who recovered fully from prolonged decerebrate rigidity associated with hypoglycemic coma. This case emphasizes the possibility of recovery from severe, prolonged hypoglycemia.

Nocturnal convulsions and insulin-induced hypoglycaemia in diabetic patients.

Convulsions may occur as a consequence of insulin-induced hypoglycaemia. We report three patients with insulin-dependent diabetes, who presented with generalized tonic-clonic seizures associated with nocturnal hypoglycaemia. None of the patients had experienced hypoglycaemia during waking hours and the convulsions were mistakenly diagnosed as idiopathic epilepsy. Recognition of the possible hypoglycaemia aetiology of these convulsions permitted appropriate alteration of the insulin regimens with no recurrence of convulsions. In one case, the seizure was associated with bilateral fractures of the neck of the humerus. Unrecognized hypoglycaemia should be considered as a possible cause of convulsions in insulin-dependent diabetic patients.

Impaired growth hormone response to growth hormone releasing factor and insulin-hypoglycaemia in obesity.

We have previously reported an impaired growth hormone (GH) response and abnormal prolactin release to insulin-hypoglycaemia in obesity. We suggested that obese women with an absent prolactin response to hypoglycaemia ('non-responders') have a disorder of hypothalamic function. We have now investigated the GH response to i.v. growth hormone releasing factor, GHRF (1-29)NH2, in 14 obese women and nine age-matched normal-weight women. We found a significantly reduced GH response to GHRF in the obese women as compared with controls (mean peak +/- SEM: obese 8.9 +/- 2 mu/l, controls 28 +/- 2 mu/l; P less than 0.01). When the obese women were divided on the basis of their prolactin response to insulin-hypoglycaemia (seven 'non-responders', mean weight 102 +/- 5 kg; seven responders, mean weight 108 +/- 8 kg) a similar GH response to GHRF was found between the two groups but the GH response to hypoglycaemia was significantly less in the 'non-responder' women (mean peak 'non-responders' 10.5 +/- 3 mu/l, responders 27 +/- 4 mu/l; P less than 0.05). We conclude that obesity may be characterized by an impaired GH response to both i.v. GHRF and insulin-hypoglycaemia, which suggests altered hypothalamic-pituitary function. The finding that the GH response to hypoglycaemia is significantly less in the obese prolactin 'non-responder' women supports the hypothesis for a hypothalamic disorder.