Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metoclopramide hydrochloride is an antiemetic and gastric motility stimulant with a wide variety of extrapyramidal side effects, including parkinsonism. We describe two patients with end-stage renal disease secondary to diabetes mellitus treated with hemodialysis who developed extrapyramidal symptoms during treatment with metoclopramide. One patient with preexisting, well-controlled Parkinson's disease developed increasing rigidity and bradykinesia that became completely refractory to treatment with L-dopa and bromocriptine while taking metoclopramide for diabetic gastroparesis. A second patient with no history of Parkinson's disease developed a resting tremor and facial dyskinesia during treatment with metoclopramide. In both cases, discontinuation of metoclopramide therapy led to prompt improvement of symptoms.
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PMID:Metoclopramide-induced parkinsonism in hemodialysis patients. Report of two cases. 376 55

This article reviews evidence for the occurrence of atypical parkinsonism in Afro-Caribbean and Indian ethnic minority subjects living in western countries, particularly the UK. Current information on the frequency, pattern, and prevalence of Parkinson's disease and parkinsonism in these communities is unclear and controversial. While several workers have suggested that there is a low prevalence of Parkinson's disease in populations of African origin, other workers have suggested a higher prevalence of Parkinson's disease in African Americans. Furthermore, little information is available in relation to the pattern of parkinsonism in these subjects. A recent phenomenologic study of parkinsonism in the French West Indies by Caparros-Lefebvre and colleagues has indicated a significantly increased frequency of atypical parkinsonism in local non-white subjects. Since 1995, we have been studying the pattern and frequency of parkinsonism in Afro-Caribbean and Indian (originating from the Indian subcontinent) patients living in the UK, with London serving as the coordinating center. Our results indicate that there is a three- to fourfold increase in the frequency of occurrence of sporadic atypical parkinsonism characterized by levodopa hyporesponsiveness, bradykinesia-dominant disease, and early cognitive dysfunction in these patients even after exclusion of patients with clinically probable multiple system atrophy, progressive supranuclear palsy, and Lewy body dementia. These findings are similar to observations made in the French West Indies. Ongoing studies in India suggest that atypical parkinsonism also affects local patients, and the pattern of parkinsonism tends to differ from Afro-Caribbean subjects in the UK. Studies are currently underway to unravel the mechanism of increased frequency of atypical parkinsonism in these ethnic groups and include genetic studies addressing polymorphisms of enzymes metabolizing levodopa, dietary neurotoxin screen and functional imaging studies of the striatum using positron emission tomography. Furthermore, the contribution of diabetes mellitus and hypertension, commonly seen in these ethnic groups, is also being examined.
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PMID:Atypical parkinsonism in Afro-Caribbean and Indian origin immigrants to the UK. 1063 37

Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. We hypothesized that the Ser311Cys mutation of DRD2 may inhibit energy expenditure. Here we report that total energy expenditure (doubly labeled water) measured in 89 nondiabetic Pima Indians was 244 kcal/ day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.056). The 24-h resting energy expenditure (respiratory chamber) measured in 320 nondiabetic Pimas was also 87 kcal/day lower in homozygotes for the Cys311-encoding allele when compared with those heterozygous and homozygous for the Ser311-encoding allele (P = 0.026). These findings are the first evidence that a genetic mutation is associated with reduced energy expenditure in humans. Because the impact of this mutation on human obesity is small, we suggest that either the energy deficit induced is not large enough to significantly influence body weight in this population and/or that the Cys311-encoding allele is also associated with reduced energy intake.
Diabetes 2001 Apr
PMID:A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure. 1128 60

Iron is essential for oxidation-reduction catalysis and bioenergetics; however, unless appropriately shielded, this metal plays a crucial role in the formation of toxic oxygen radicals that can attack all biological molecules. Organisms are equipped with specific proteins designed for iron acquisition, export and transport, and storage, as well as with sophisticated mechanisms that maintain the intracellular labile iron pool at an appropriate level. Despite these homeostatic mechanisms, organisms often face the threat of either iron deficiency or iron overload. This review describes several hereditary iron-overloading conditions that are confined to the brain. Recently, a mutation in the L-subunit of ferritin has been described that causes the formation of aberrant L-ferritin with an altered C-terminus. Individuals with this mutation in one allele of L-ferritin have abnormal aggregates of ferritin and iron in the brain, primarily in the globus pallidus. Patients with this dominantly inherited late-onset disease present with symptoms of extrapyramidal dysfunction. Mice with a targeted disruption of a gene for iron regulatory protein 2 (IRP2), a translational repressor of ferritin, misregulate iron metabolism in the intestinal mucosa and the central nervous system. Significant amounts of ferritin and iron accumulate in white matter tracts and nuclei, and adult IRP2-deficient mice develop a movement disorder consisting of ataxia, bradykinesia, and tremor. Mutations in the frataxin gene are responsible for Friedreich's ataxia, the most common of the inherited ataxias. Frataxin appears to regulate mitochondrial iron-sulfur cluster formation, and the neurologic and cardiac manifestations of Friedreich's ataxia are due to iron-mediated mitochondrial toxicity. Patients with Hallervorden-Spatz syndrome, an autosomal recessive, progressive neurodegenerative disorder, have mutations in a novel pantothenate kinase gene (PANK2). The cardinal feature of this extrapyramidal disease is pathologic iron accumulation in the globus pallidus. The defect in PANK2 is predicted to cause the accumulation of cysteine, which binds iron and causes oxidative stress in the iron-rich globus pallidus. Finally, aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by loss-of-function mutations in ceruloplasmin gene that leads to misregulation of both systemic and central nervous system iron trafficking. Affected individuals suffer from extrapyramidal signs, cerebellar ataxia, progressive neurodegeneration of retina, and diabetes mellitus. Excessive iron depositions are found in the brain, liver, pancreas, and other parenchymal cells, but plasma iron concentrations are decreased. These conditions are not common, but awareness about them is important for differential diagnosis of various neurodegenerative disorders.
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PMID:Hereditary causes of disturbed iron homeostasis in the central nervous system. 1510 72

Studies have shown that parkinsonian signs are related to cognitive function in aging. What remains unclear is whether this association is stronger for some cognitive domains than it is for others, and precisely how much variability in global and specific cognitive functions is explained by the motor signs. We examined the associations between four parkinsonian signs (gait, rigidity, bradykinesia, tremor) and five cognitive domains (episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability) in a large cohort of older persons who were free of Parkinson's disease and dementia and were participating in the Rush Memory and Aging Project. In a series of regression equations that controlled for age, sex, and education, higher levels of three signs (gait, rigidity, and bradykinesia) were related to lower levels of cognitive function, but they accounted for less than 5% of the variance in most measures. The results did not change when the presence of depressive symptoms, diabetes, and hypertension were added to the models. The cross-sectional association between parkinsonian signs and cognitive function did not vary substantially across specific cognitive domains or specific cognitive tests. The results suggest that parkinsonian signs have a modest, but statistically reliable, association with level of cognitive function in old age.
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PMID:Parkinsonian signs and cognitive function in old age. 1621 86

We examined the relation of type 2 diabetes mellitus to parkinsonian signs in older persons. Participants were 1030 women and men (mean age 80.3 y, education 14.5 y, Mini-Mental State Examination 27.9) without dementia or Parkinson disease, enrolled in the Rush Memory and Aging Project, an epidemiologic study of aging. We used separate linear and logistic regression models, adjusted for age, sex, and education, to examine the relation of diabetes, identified by history and medication inspection, to each of the scores of global parkinsonian signs and 4 separate parkinsonian signs. Diabetes was present in 140 (14%) participants. Most participants had mild parkinsonian signs. Diabetes was associated with a more severe global parkinsonian signs score (beta=0.20, SE=0.10, P=0.05) and postural reflex impairment-gait disturbance (beta=0.40, SE=0.17, P=0.02), but not with bradykinesia, rigidity, or tremor. Associations were no longer significant after controlling for vascular risk factors or conditions, particularly body mass index and congestive heart failure. Overall, there was no evidence that vascular variables modified the relation of diabetes to parkinsonian signs. In summary, we found that diabetes was associated with parkinsonian signs, especially postural reflex impairment-gait disturbance, and that vascular factors may play a role in this association.
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PMID:Diabetes and parkinsonian signs in older persons. 1754 40

Acute movement disorder associated with reversible bilateral basal ganglia lesions is an increasingly recognized syndrome in patients with end-stage renal disease, especially in the setting of concurrent diabetes mellitus. We report an elderly man with end-stage diabetic nephropathy treated by daily automated peritoneal dialysis who developed subacute symptoms of gait disturbance, dysarthria, dysphagia and lethargy. Computed tomography and magnetic resonance imaging of the head revealed bilateral symmetrical basal ganglia lesions. Repeat imaging 3 weeks later showed that these lesions had regressed spontaneously. However, his neurological symptoms improved slowly. These findings were similar to 23 other cases in the literature. Review of these cases shows that clinical features were predominantly bradykinesia, gait disturbance and concurrent metabolic acidosis (observed in 90% of cases). The pathogenesis of this condition has not been clearly defined, but uraemia may be an aggravating factor in predisposed patients, particularly in the presence of diabetic microvascular disease. There is no specific treatment for this condition; supportive measures are the mainstay of management. In the majority of patients, neurological improvement lags behind regression of basal ganglia lesions seen with neuroimaging, and the long-term outcome is variable.
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PMID:Bilateral basal ganglia lesions in patients with end-stage diabetic nephropathy. 1819 7

Parkinson's disease is a neurodegenerative disorder clinically characterized by motor impairments (tremor, bradykinesia, rigidity and postural instability) associated or not with non-motor complications (cognitive disorders, dysautonomia). Most of patients loose weight during evolution of their disease. Dysregulations of hypothalamus, which is considered as the regulatory center of satiety and energy metabolism, could play a major role in this phenomenon. Deep brain stimulation of the subthalamic nucleus (NST) is an effective method to treat patients with advanced Parkinson's disease providing marked improvement of motor impairments. This chirurgical procedure also induces a rapid and strong body weight gain and sometimes obesity. This post-operative weight gain, which exceeds largely weight lost recorded in non-operated patient, could be responsible of metabolic disorders (such as diabetes) and cardiovascular diseases. This review describes body weight variations generated by Parkinson' disease and deep brain stimulation of the NST, and focuses on metabolic disorders capable to explain them. Finally, this review emphasizes on the importance of an adequate nutritional follow up care for parkinsonian patient.
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PMID:[The Idiopathic Parkinson's disease: A metabolic disease?]. 2083 92

The risk of developing a movement disorder increases with age. Idiopathic Parkinson's disease (IPD), is probably the most well known. However, essential tremor is the most common movement disorder affecting older people. Although many sufferers can have very disabling symptoms it can be a very mild illness in some. Patients present with a symmetrical tremor of the upper limbs in 95% of cases. The tremor is less evident at rest, unlike the tremor of IPD, and there will be no rigidity or bradykinesia. Essential tremor is a mainly clinical diagnosis. A watchful waiting period may be tried. DaTSCAN can be helpful as the results will be normal in patients with essential tremor and abnormal in those with IPD. Vascular parkinsonism accounts for 4.4-12% of all cases of parkinsonism, although it is likely that many cases remain undiagnosed. The features are usually bilateral and symmetrical and often affect the lower more than the upper limbs. A history of previous stroke is common, as are the presence of cardiovascular risk factors such as hypertension and diabetes. Drug-induced parkinsonism is the second most common cause of parkinsonism behind IPD. All patients thought to have a diagnosis of possible IPD should be referred to secondary care. It would also be prudent to refer any patients whose diagnosis is unclear and where advice would be helpful on future management.
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PMID:Diagnosing non-parkinson's movement disorders. 2249 5

In this article, we present 3 women aged 73, 85 and 88 years who developed metoclopramide-induced parkinsonism. Shortly after starting metoclopramide, bradykinesia and rigidity developed in all 3 patients; tremor and postural instability in 2 of them. We discontinued the metoclopramide after 3-6 months; 2 of the patients had fully recovered 4-6 months later. The 3rd patient died from pneumonia, however, 2 months after discontinuation. Metoclopramide, a dopamine D2-antagonist, is a frequently prescribed anti-emetic drug; however, evidence of its efficacy is limited. In many patients, domperidone, another dopamine D2-antagonist, seems to be a better alternative. Movement disorders due to domperidone are uncommon, presumably because it does not cross the blood-brain barrier. It is likely that metoclopramide-induced parkinsonism is not uncommon; however, it is under-recognized. Risk factors are female sex, advanced age, diabetes mellitus and polypharmacy. Follow-up on patients using metoclopramide is advised.
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PMID:[Severe parkinsonism due to metoclopramide: the importance of early recognition]. 2383 36


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