Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a group of 365 subjects, 75 years old and ultra, living in Troina (Sicily), a study on prevalence of dementia has been carried out. In the questionnaire, used to collect information about subjects' health, one of the questions concerned the assumption of drugs. The interviewer transcribed the name of the drugs and then coded the related chemical-pharmacological classification, according to the 14 principal groups of the guide of the National Health Service. Up to 9 drugs, on a daily basis, were registered. The total amount of prescriptions was 889, equal to 2.4 per person, with a clear prevalence of the females. 26.1% of the sample did not take any drug. The mode of assumptions was 3 a day. The cardiovascular system is at the top of prescriptions, with 39% of the total, followed by the gastroenteric apparatus and metabolism (17.9%), the nervous system (16.7%), the haemopoietic system (8.4%), the musculo-skeletal system (6.2%), the respiratory apparatus (5.7%), and so on the others. For each principal group of drugs, those more represented are identified, obtaining other information about the practitioners' choices. Among the principal subgroups of cardiovascular system, it is worth mentioning anti-hypertensives, diuretics and antianginal, each of them with their own subgroups. In the gastroenteric apparatus and metabolism group, the latter comprises the drugs for the treatment of diabetes: oral hypoglicaemics and insulin. These drugs allow to identify 34 cases of diabetes: 29 NIDD and 5 IDD. Analogous evaluations for drugs of other groups and comparisons with a few data available in literature are carried out. Surveying the drugs used in a population is useful: (i) to evaluate the health state; (ii) to identify the dominant disease; (iii) to draw comparisons with other populations; (iiii) to follow the evolution of pharmacotherapy.
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PMID:Home pharmacological therapy in an ultra-75 years old population in Troina (inner Sicily). 963 Jul 56

This review describes the cerebral complications of diabetes mellitus from a neuropsychological, neurophysiological and neuroradiological perspective. In addition, possible pathogenetic mechanisms are discussed. Neuropsychological studies of diabetic patients generally report modest deficits in learning and memory and information processing. Notably, in elderly diabetic patients cognitive deficits may be more prominent. Recent epidemiological studies show that in the elderly diabetes is associated with an increased risk for dementia. Neurophysiological studies show increased latencies of evoked potentials and event-related potentials. Neuroradiological findings are enhanced peripheral and central cerebral atrophy, as well as focal lesions. The pathophysiology of the effects of diabetes on the brain has not been fully elucidated. The putative involvement of cerebral metabolic and microvascular disturbances, similar to those implicated in the pathogenesis of peripheral diabetic neuropathy, is discussed. In addition, the role of repeated hypoglycaemic episodes, cerebrovascular disease and hypertension is addressed. Finally, the potential differential effects of insulin dependent and non-insulin dependent diabetes on the brain are discussed, as well as possible links with brain ageing.
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PMID:Cerebral complications of diabetes: clinical findings and pathogenetic mechanisms. 1007 78

Type 1 diabetes mellitus correlates with several brain disturbances, including hypersensitivity to stress, cognitive impairment, increased risk of stroke and dementia. Within the central nervous system, the hippocampus is considered a special target for alterations associated with diabetes. Neurogenesis is a plastic event restricted to few adult brain areas: the subgranular zone of the dentate gyrus and the subventricular zone (SVZ). First, we studied the ability for neurogenesis in the dentate gyrus and SVZ of chronic diabetic mice induced by streptozotocin (STZ). Using bromodeoxyuridine (BrdU) labelling of cells in the S-phase, we observed a strong reduction in cell proliferation rate in both brain regions of diabetic mice killed 20 days after STZ administration. Second, because oestrogens are active neuroprotective agents, we investigated whether 17beta-oestradiol (200 micro g pellet implant in cholesterol during 10 days) restored brain cell proliferation in the diabetic mouse brain. Our results demonstrated a complete reversibility of dentate gyrus cell proliferation in oestrogen-treated diabetic mice. This plasticity change was not exclusive to the hippocampus because oestrogen treatment restored BrdU incorporation into newborn cells of the SVZ region of diabetic animals. Oestrogen treatment did not alter the hyperglycemic status of STZ-diabetic mice. Moreover, oestrogen did not modify BrdU incorporation in control animals. These data show that oestrogen treatment strongly stimulates brain neurogenesis of diabetic mice and open up new venues for understanding the potential neuroprotective role of steroid hormones in diabetic encephalopathy.
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PMID:Oestradiol restores cell proliferation in dentate gyrus and subventricular zone of streptozotocin-diabetic mice. 1527 Oct 63

Diabetes mellitus is associated with modest impairments in cognition, particularly in the elderly. In addition, the risk of dementia is increased. We review herein studies in rodent models that may help to identify the mechanisms that underlie these adverse effects of diabetes on the brain. Abnormalities in learning and memory, synaptic plasticity, and glutamatergic neurotransmission have now been identified in a number of these models. In general, observations in models characterized by chronic hyperglycaemia and hypoinsulinaemia (referred to as models of type 1 diabetes) are quite consistent, and these models are being increasingly used to study the pathogenesis and to develop new treatments. However, results from models characterized by insulin resistance, hyperinsulinaemia, and modest hyperglycaemia (referred to as models of type 2 diabetes) are much more variable. Moreover, the possible interaction between diabetes and aging has not been examined in sufficient detail. Because clinically relevant cognitive deficits mainly occur in elderly patients with type 2 diabetes, the challenge for researchers in this field will be to further develop adequate models.
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PMID:The impact of diabetes on cognition: what can be learned from rodent models? 1622 48

Data from 1294 patients with diabetes mellitus admitted to the Endocrinology Department of the Institute of Medical Sciences, Srinagar, Kashmir, from 1986 to 1994, were analyzed for frequency of various neurological problems. Of 1294 patients, 46.29% had clinical evidence of one or more neurological problems. The frequency of neurological problems was significantly more in patients with type II diabetes mellitus (P<0.001). Predominant neurological problems included peripheral neuropathy (96.66%), stroke (5.51%), Parkinsonism (1.50%), seizure disorder (1.17%) and dementia (1%). Mean (+/- SD) age of patients with neurological problems was significantly more (P<0.001) than those without neurological problems (52.07+/- 9.52 versus 47.45+/- 12.87 years for type II diabetes mellitus; 26.73+/- 8.40 versus 18.0+/- 3.62 for type I diabetes mellitus). Mean duration of diabetes in patients with neurological problems was significantly more than those without neurological problems (6.70+/- 6.04 versus 3.95+/- 4.22 years for type II diabetes mellitus; 5.63+/- 3.67 versus 1.89+/- 2.57 for type I diabetes mellitus). At the time of admission, fasting blood glucose was lower in patients without neurological problems as compared to patients with problems (9.08+/- 2.22 versus 11.05+/- 4.91 mmol/L for type II diabetes mellitus; 9.44+/- 2.80 versus 13.01+/- 5.01 mmol/L for type I diabetes mellitus; P7lt;0.001).
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PMID:Profile of neurological problems in diabetes mellitus retrospective analysis of data from 1294 patients. 1737 58

Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl-tryptophan causes a sudden catastrophic rejection of the mammalian fetus. Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells. Thus it makes sense to consider IDO induction towards tolerance for autoimmune diseases in general. Approaches to cell specific therapeutic IDO induction with NAD precursor supplementation to prevent the collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an essential amino acid most immediately because it is the only precursor for the endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both autoimmune disease and the NAD deficiency disease pellagra occur in women at greater than twice the frequency of occurrence in men. The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to psychotic symptoms rapidly progressing to presenile dementia likely due to unchecked increases in microglial IDO expression, which depletes neurons of tryptophan causing neurodegeneration. Administration of NAD precursors rescued entire mental hospitals of dementia patients literally overnight in the 1930's and NAD precursors should help Nasu-Hakola patients as well. NAD depletion mediated by peroxynitrate PARP1 activation is one of the few established mechanisms of necrosis. Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD. Pharmacological doses of NAD precursors repeatedly provide dramatic therapeutic benefit for rheumatoid arthritis, type 1 diabetes, multiple sclerosis, colitis, other autoimmune diseases, and schizophrenia in either the clinic or animal models. Collectively these observations support the idea that autoimmune disease may in part be considered as localized pellagra manifesting symptoms particular to the inflamed target tissues. Thus pharmacological doses of NAD precursors (nicotinic acid/niacin, nicotinamide/niacinamide, or nicotinamide riboside) should be considered as potentially essential to the therapeutic success of any IDO-inducing regimen for treating autoimmune diseases. Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2). Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2). These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively. Nicotinamide prevents type 1 diabetes and ameliorates multiple sclerosis in animal models, while nothing is known about the therapeutic potential of nicotinamide riboside. Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.
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PMID:Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease. 1743 Jan 13

An increased research interest in the relation between diabetes mellitus and dementia or deterioration of cognitive functions has been recently noticed. The relatively rich scientific literature in this topic shows that diabetes mellitus itself can cause an impairment of cognitive functions regardless patient's age or the fact whether he has type 1 or type 2 diabetes mellitus. Type 1 diabetes mellitus leads to a psychomotor retardation while type 2 diabetes mellitus tends to be associated with impaired storage of new information. The exact mechanism through which diabetes impairs cognition has not been explained sufficiently yet, but several hypothetical mechanisms which might explain the relation between diabetes and impaired cognition have been proposed. To explain the etiopathogenetic mechanisms underlying the relation between diabetes and dementia, further research, especially research focused on process clinical-imaging studies or clinical-pathological studies is necessary. As far as clinical practice is concerned, it is important to bear in mind that prevention, timely diagnosis and optimum treatment of diabetes may help to reduce incidence of dementia or cognitive functions' impairment.
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PMID:[Cognitive functions impairment in diabetes mellitus patient]. 1755 64

Type 1 diabetes may be associated with a mild decline in cognitive function and mostly in mental speed. In order to study the pathophysiology of this, we have investigated auditory event-related potentials (AERP) and their relation to cognitive function in diabetes patients. AERP was recorded in patients with type 1 diabetes (n=119) and in a healthy control group (n=61). AERP was obtained with an odd-ball and a two-stimulus paradigm. Cognitive function was evaluated in 10 domains in the patients. Patients had normal N100 latency, but a highly significant decrease in auditory N100 amplitude (p<10(-6)), which correlated with a decrease in psychomotor speed but not with function in other domains. Psychomotor speed also correlated with P300 amplitude, although P300 amplitude was only slightly decreased in the patients. Even stronger correlations were found with the parietal N100-P300 peak-to-peak amplitude, which correlated both to psychomotor speed (rho=0.61, p<10(-7)) and processing speed (p<0.005). P300 latency was increased in patients, and this correlated to low global cognitive score and older age. We conclude that the decline in psychomotor speed in type 1 diabetes is associated with a highly significant decrease in the auditory N100 peak amplitude. This association and the relatively small abnormality in P300 latency is quite different from those generally found in dementia, and suggest that the underlying defect is located in the brain stem or the white matter. Presumably small conduction defects in ascending fibers can distort the firing synchrony necessary for signal generation in the cortex.
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PMID:Cognitive impairment correlates to low auditory event-related potential amplitudes in type 1 diabetes. 1865 25

Glucose is almost the only energy substrate for the brain. Such glucose dependence explains why any large variation of plasma glucose levels could lead to cerebral dysfunction, which may be severe and progress to a coma. Hypoglycaemic coma, the most common one, has a pure metabolic origin (neuroglucopenia) whereas hyperglycaemic coma is more complex and mainly due to osmotic disturbances. Besides acute changes of plasma glucose concentrations, it is generally recognized that more subtle chronic or recurrent glucose abnormalities could also result in brain dysfunction. However, such clinical consequences are more difficult to assess in clinical practice. Nevertheless, learning perturbations in young patients with type 1 diabetes and memory losses, sometimes severe and subject to progress to dementia ("diabetic encephalopathy") in older type 1 or type 2 diabetic patients, have been reported, although with some controversy. The present paper summarizes the current knowledge of both acute and chronic cerebral dysfunctions following perturbations of blood glucose levels in diabetic patients.
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PMID:[Brain, a gluco-dependent organ: toxic effects of hypoglycaemia and hyperglycaemia]. 1866 93

The occurrence of diabetes and dementia is very high in older patients. The fact that both conditions are concurrent raises the question of a possible link between the two. Cognitive functions of non-demented patients with diabetes have been extensively studied. In type 1 diabetes, only a mild decrease of the speed of information processing and of the psychomotor efficiency has been shown. Cognitive decline seems to be related to poor metabolic control and not to hypoglycaemia. In older patients with type 2 diabetes, memory and executive functions have been found impaired. Longitudinal studies of the literature have shown that diabetic patients have a higher chance of developing dementia than non-diabetic patient, with a relative risk (RR) between 1.26 and 2.83. The risk of vascular dementia was increased in 3 out of 5 studies, with a RR ranging between 2 and 2.6. With regard to Alzheimer's disease, the results are conflicting. Half of the studies found an increased risk in diabetic patients (RR: 1.3-2). The possible causal mechanisms of dementia in diabetic patients remain hypothetical. MRI studies showed varying degrees of cortical atrophy, cerebral infarcts and deep white matter lesions. In neuropathological studies, senile plaques and neurofibrillary tangle were not found with higher severity in the brain of diabetic patients than in the brain of age-matched controls. Several hypotheses have been raised to explain the relationship between diabetes and cognitive decline. Micro and macrovascular changes in the brain could induce cerebral hypoxia and ischemic conditions resulting in cellular death or white matter lesions. The occurrence of vascular lesions might reduce the threshold at which dementia will occur in Alzheimer disease. The deposition of advanced glycation end products doesn't spare the brain and they have been found in senile plaques, where they can reduce the solubility of proteins such as the beta amyloid and Tau proteins. Some authors favour the hypothesis of a brain insulin resistance because, in a few small studies, insulin was found to improve memory.
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PMID:[Diabetes mellitus and cognition: is there a link?]. 1878 78


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