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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Driving is a complex, multi-task activity that can be affected by cognitive impairment resulting from episodes of severe hypoglycaemia. Intensive insulin therapy increases the likelihood of severe hypoglycaemia but there have been few studies examining effects on driving skills. A survey carried out recently indicated that patients with type 1 diabetes had twice the incidence of driving accidents than their non-diabetic spouses or patients with type 2 diabetes. The motor accidents were associated with more frequent low blood glucose while driving and less frequent self-monitoring. In driving simulation tests it was found that driving has an intrinsic metabolic demand that can contribute to hypoglycaemia. Driving performance began to deteriorate at around 3.6 mmol/l but drivers frequently did not recognise and failed to treat the hypoglycaemia. Those who did self-treat had more driving relevant symptoms and less neuroglycopenia quantified by EEG alpha-theta differences. Patients should be recommended not to begin driving if blood glucose is below 4.5 mmol/l and should not continue to drive if they suspect that blood glucose has fallen below 4 mmol/l while driving. If hypoglycaemia is suspected patients should immediately pull off the road, measure blood glucose if possible, treat themselves as necessary and not resume driving until glucose and cognitive-motor function return to normal. The problems of driving and hypoglycaemia should be discussed with patients with diabetes and behavioural interventions instigated. To this end, Blood Glucose Awareness Training (BGAT) and Hypoglycaemia Anticipation, Awareness and Treatment Training (HAATT) have been developed and shown to markedly reduce incidence of driving mishaps.
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PMID:Driving mishaps and hypoglycaemia: risk and prevention. 1159 97

Hyperhomocysteinemia (HHcy) is a metabolic disorder frequently occurring in the elderly population. Recently several reports have suggested abnormalities in homocysteine (tHcy) metabolism implicating HHcy as a metabolic link in the multifactorial processes characterizing many geriatric illnesses-with special emphasis on atherosclerotic vascular diseases and cognitive impairment. The present study was undertaken in a large sample of elderly hospitalized subjects to determine (1) the prevalence of HHcy, (2) the association of HHcy with vascular and cognitive disorders, and (3) the factors independently predicting Hhcy. Six hundred elderly subjects (264 men and 336 women; mean age, 79 +/- 9 years) were randomly chosen from those admitted as inpatients over a period of 3 years. In all patients, body mass index (BMI), mid-upper arm muscle area (MUAMA), plasma cholesterol, triglycerides, total proteins, albumin, lymphocyte count, creatinine, homocysteine (fasting and 4 hours after methionine oral load), serum vitamin B(6), vitamin B(12), and folate concentrations were measured. The presence of disease or use of medications known to affect homocysteine plasma levels were also recorded. The mean fasting tHcy level was 16.8 +/- 12 micromol/L in the whole sample, 18.18 +/- 13.25 micromol/L in men, and 15.86 +/- 12.14 micromol/L in women (P =.005 men v women). The mean Hcy level 4 hours after methionine load was 37.95 +/- 20.9 in the whole sample. Prevalence of hyperhomocysteinemia (fasting Hcy > or = 15 micromol/L or 4 hours after methionine load > or = 35 micromol/L) was 61% (365/600) (67% in men and 56% in women, P <.05). HHcy was rarely (8%) an isolated disorder; in addition to diabetes (20%), renal failure (48.2%), and malnutrition (20.2%), it was often associated with heart failure (30%), malignancies (20.5%), and the use of diuretics (56%) and anticonvulsant drugs (13%). Plasma homocysteine progressively increases across subjects from those with no diabetes, malnutrition, renal failure, obesity, inflammatory bowel disease, heart failure to those with 1, 2, or more concurrent diseases. Multiple stepwise regression analysis showed that 72% of plasma total fasting tHcy variability was explained by age, serum folate, plasma albumin, use of diuretics, and renal function (measured as plasma creatinine clearance). In conclusion, the present study documents that hyperhomocysteinemia, in elderly hospitalized patients is (1) a common finding, (2) frequently associated with vascular and cognitive disorders, and (3) probably a secondary phenomenon in most cases. The major predictor of high plasma homocysteine levels were age, serum folate, plasma albumin, plasma creatinine clearance, and use of diuretic drugs. These variables explain a large proportion of plasma Hcy variability.
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PMID:Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects. 1173 95

Five female patients developed chorea concurrent with, or shortly after a hyperglycemic episode (admission glucose values 500-1,000 mg/dL). In four of these five patients, there was no prior history of diabetes mellitus. The chorea continued despite correction of blood glucose and persisted to the time of last follow-up, 6 months to 5 years later. The chorea developed subacutely over 2 days to 1 month and was generalized in one, unilateral in three, and involved right > left lower extremity in the other; the severity initially reached ballistic proportions in two. Associated clinical features were nil in four of these patients, but cognitive impairment and personality change occurred in one. The histories and laboratory studies identified no predisposing factors other than the hyperglycemia. The chorea was sufficiently troublesome to require administration of neuroleptic medication in all five cases. Four of the five cases had high signal intensity within basal ganglia on T1-weighted magnetic resonance (MR) imaging, as has previously been described; however, this was not seen in one case (who had the most severe clinical condition). Most previously described cases have involved a reversible clinical syndrome, in contrast to our patients. The pathogenic mechanisms remain uncertain.
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PMID:Persistent chorea triggered by hyperglycemic crisis in diabetics. 1174 19

The main therapeutic challenge in the treatment of Type 1 diabetes is maintenance of near-normoglycaemia in order to prevent long-term complications and avoid hypoglycaemia. This goal is relevant from the onset of the disease and is feasible if physiological models of insulin replacement are used and patients are educated in the strategy of intensive insulin therapy. Although the use of available insulins within a multiple injection regimen has improved, metabolic control it is still far from being optimal. The recent introduction of insulin analogues with a short- and long-acting profile seems promising in improving metabolic control and quality of care. Insulin lispro and insulin aspart, the short-acting insulin analogues offer a better post-prandial profile, while insulin glargine the new long-acting insulin analogue might provide better overnight control. In fact, the theoretical combination of an acute prandial insulin peak with a flat interprandial and overnight plasma profile would closely mimic the 24-hr insulin profile of non-diabetic individuals. This would possibly lead to lower post-prandial blood glucose excursion and better fasting blood glucose associated with minimal risk of hypoglycaemia. The possible reduction of hypoglycaemia is especially important in children as recurrent episodes might represent a potential risk for cognitive impairment. However, recent clinical research on the short-acting insulin analogues demonstrates the difficulties of translating these theoretical benefits into clinical relevant advantages. This might happen to other insulin analogues and requires further and larger studies in order to fully exploit the theoretical advantages of insulin analogues in the paediatric population. Safety issues should also be carefully monitored when introducting analogues in long-term therapy.
Diabetes Nutr Metab 2001 Dec
PMID:The potential role of insulin analogues in the treatment of children and adolescents with Type 1 diabetes mellitus. 1185 68

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.
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PMID:Hypoglycaemia unawareness and the brain. 1213 93

Duration-related cognitive impairment is an increasingly recognized complication of type 1 diabetes. To explore potential underlying mechanisms, we examined hippocampal abnormalities in the spontaneously type 1 diabetic BB/W rat. As a functional assay of cognition, the Morris water maze test showed significantly prolonged latencies in 8-month diabetic rats not present at 2 months of diabetes. These abnormalities were associated with DNA fragmentation, positive TUNEL staining, elevated Bax/Bcl-x(L) ratio, increased caspase 3 activities and decreased neuronal densities in diabetic hippocampi. These changes were not caused by hypoglycemic episodes or reduced weight in diabetic animals. To explore potential mechanisms responsible for the apoptosis, we examined the expression of the IGF system. Western blotting and in situ hybridization revealed significant reductions in the expression of IGF-I, IGF-II, IGF-IR and IR preceding (2 months) and accompanying (8 months) the functional cognitive impairments and the apoptotic neuronal loss in hippocampus. These data suggest that a duration-related apoptosis-induced neuronal loss occurs in type 1 diabetes associated with cognitive impairment. The data also suggest that this is at least in part related to impaired insulin and/or IGF activities.
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PMID:Hippocampal neuronal apoptosis in type 1 diabetes. 1213 25

Epidemiologic literature suggests that persons with clinically diagnosed sleep apnoea frequently have impaired cognitive function, but whether milder degrees of sleep-disordered breathing (SDB) are associated with cognitive dysfunction in the general population is largely unknown. Approximately 1700 subjects free of clinically diagnosed SDB underwent at-home polysomnography (PSG) as part of the Sleep Heart Health Study (SHHS) and completed three cognitive function tests within 1-2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS-R Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. After adjustment for age, education, occupation, field centre, diabetes, hypertension, body-mass index, use of CNS medications, and alcohol drinking status, there was no consistent association between the RDI and any of the three cognitive function measures. There was no evidence of a dose-response relation between the RDI and cognitive function scores and the adjusted mean scores by quartiles of RDI never differed from one another by more than 5% for any of the tests. In this sample of free-living individuals with mostly mild to moderate levels of SDB, the degree of SDB appeared to be unrelated to three measures of cognitive performance.
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PMID:Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study. 1222 Mar 23

This paper discusses the hypothesis that the cerebrometabolic deficiency in Alzheimer's disease(AD) is the proximate cause of the clinical disability. Several sets of observations support this hypothesis. (1) Impaired brain metabolism essentially always occurs in clinically significant AD, and the degree of clinical disability is proportional to the degree of metabolic impairment. The earliest, mildest changes in brain metabolism occur even before the onset of measurable cognitive impairment or atrophy. This observation disproves the now outdated assumption that the decreased metabolism is simply a consequence of decreased mental function or of atrophy. One of the important mechanisms reducing brain metabolism in AD appears to be damage to key mitochondrial components. Another appears to relate to inappropriate responses to insulin, i.e. to diabetes of the brain. (2) Inducing impairments of brain metabolism causes changes in mentation that mimic the clinical disabilities in AD, in both humans and experimental animals. (3) Preliminary results from several units suggest that treatment directed at the impairment of brain metabolism can improve neuropsychological functions in AD patients. The hypothesis presented here in no way negates the importance of other mechanisms in AD, such as amyloid accumulation, vascular compromise, and free radical action. However, those other abnormalities including amyloidosis can occur in people whose mentation is still clinically unimpaired. In contrast, once significant decrease in the rate of brain metabolism occurs, mentation becomes defective.
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PMID:The role of the metabolic lesion in Alzheimer's disease. 1222 41

Issues to consider when evaluating maintenance drug therapy for patients with schizophrenia are discussed; these include potential adverse effects of antipsychotic therapy, such as weight gain, diabetes mellitus, extrapyramidal symptoms, sexual dysfunction, cognitive dysfunction, and cardiac effects, as well as quality of life. Patients with schizophrenia are more likely to be overweight than the general population. Olanzapine and clozapine have been associated with the greatest weight gain of the newer antipsychotics. While patients with schizophrenia are at increased risk of developing diabetes mellitus independent of antipsychotic therapy, diabetes may be more prevalent in patients taking the newer agents. Acute extrapyramidal symptoms occur in 75-90% of patients receiving first-generation antipsychotics like thioridazine and haloperidol. The probability of tardive dyskinesia (TD) occurring with second- and third-generation agents is less than 1% per year, compared with about 5% per year for the traditional antipsychotics. When patients are switched from a traditional antipsychotic to clozapine or olanzapine, TDs usually abate somewhat. Thioridazine causes a pronounced prolongation of the QTc interval, which can lead to ventricular arrhythmias. The slight increase in QTc interval caused by ziprasidone most likely will not be a problem in healthy individuals. Newer antipsychotics are associated with improved neurocognitive functioning and most cause less prolactin elevation, compared with traditional agents. The newer antipsychotic agents are not devoid of adverse effects, but those that do occur can be managed. Once issues related to adherence are resolved, rehabilitation of patients with schizophrenia will be a high priority.
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PMID:Clinical issues associated with maintenance treatment of patients with schizophrenia. 1222 83

Cognitive decline is a significant but largely unrecognized sequela following irradiation for several head and neck tumors, particularly cancer of the nasopharynx and paranasal sinuses. In this article the cellular mechanisms of radiation-induced vascular damage in the temporal lobe and its effects on the medial temporal lobe memory systems are described. Recognition of the mechanisms and site of the injury should permit the use of treatment planning systems, such as 3-dimensional (3-D) conformal and intensity-modulated radiotherapy (IMRT) techniques, to spare large volumes of the temporal lobe from receiving a high dose. Furthermore, the emerging concepts of vascular irradiation damage as an inflammatory fibroproliferative response to endothelial injury may permit the application of measures directed at inhibiting the expression of proinflammatory genes and thus mitigate the inflammatory response. Moreover, comorbid factors such as hypertension, diabetes, lipidemia, obesity and smoking are known to promote atherogenesis and therefore may exacerbate radiation-induced vascular damage. Control of these factors may also reduce the incidence and severity of this sequela.
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PMID:Pathogenesis of cognitive decline following therapeutic irradiation for head and neck tumors. 1223 25


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