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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study shown an abnormality in glucagon levels that may explain the glucose intolerance, abnormal insulin reactions, and abnormal plasma amino acid levels seen in amyotrophic lateral sclerosis (ALS). We randomly administered two test meals, differing only in protein source (soy versus casein) at least 1 week apart and measured fasting and postprandial bloods for glucagon, insulin, and glucose levels in 11 ALS patients. With the soy test meal, glucagon levels were elevated in all ALS patients compared with controls: at fasting (237 +/- 111 versus 108 +/- 46 pg/ml, p less than 0.01) and 1/2 hour (389 +/- 94 versus 133 +/- 68 pg/ml, p less than 0.001), and 2 hours postprandial (379 +/- 75 versus 108 +/- 53 pg/ml, p less than 0.001). Glucagon levels after the casein test meal were also significantly elevated. Insulin was elevated by both test meals. Casein produced significant glucose intolerance.
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PMID:Elevated plasma glucagon in amyotrophic lateral sclerosis. 849 33

1. The effect of muscle wasting on glucose tolerance was studied. Oral glucose tolerance testing was performed in three groups of wasted patients: myotonic dystrophy (11); amyotrophic lateral sclerosis (10); other lower motor neuron disease (four). Normal subjects (11) and non-wasted neurological disease (five) controls were studied for comparison. An average decrease of 29-36% in lean body mass was present in the wasted individuals. 2. A slightly higher plasma glucose occurred at 120 min after glucose ingestion in wasted compared with non-wasted individuals (119.2 +/- 5 vs. 99.9 +/- 4 mg/100 ml, P less than 0.05). 3. Normal insulin release was seen in all patient groups except those with myotonic dystrophy, who displayed marked hyperinsulinaemia from 30 to 240 min after glucose. This excessive insulin output was not due to a greater absolute decrease in lean body mass in the myotonic dystrophy patients than in the other wasted subjects. No significant correlation between the cumulative insulin release or peak insulin values and the absolute or height adjusted lean body mass was noted within any of the wasted or non-wasted groups. 4. In contrast to the findings of many studies, only clinically insignificant glucose intolerance was detected in ambulatory wasted patients and only patients with myotonic dystrophy had abnormal insulin release. Muscle loss appeared to exert only a slight influence on glucose regulation in these wasted patients and no typical effect of muscular atrophy on pancreatic insulin release was noted.
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PMID:Influence of muscle wasting on oral glucose tolerance testing. 634 Sep 18

Over the last 30 years glucose intolerance has been reported in a significant percentage of patients with amyotrophic lateral sclerosis (ALS). Currently, a controversy exists in determining whether the carbohydrate abnormality is disease-specific or secondary to decreased glucose utilization due to muscle atrophy. A reduction in glucose receptor space had been postulated for a number of neuromuscular diseases including ALS. In order to clarify this issue we have estimated in vivo insulin sensitivity, using the euglycemic insulin clamp technique, in ALS patients and two control groups, matched according to percent ideal weight. The results showed that the glucose infusion rate, an estimate of in vivo insulin sensitivity, ws significantly diminished in ALS patients compared to both normal and disease controls. These results demonstrate that the insulin resistance in this disorder cannot be explained by a decrease in glucose-receptor space and suggest a primary carbohydrate aberration in the disease process itself.
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PMID:Insulin resistance in amyotrophic lateral sclerosis. 637 40

Blood glucose and plasma insulin during an oral glucose tolerance test were determined in 21 patients with amyotrophic lateral sclerosis and in 10 control patients matched for age, obesity and physical activity. In addition, 125I-insulin binding to circulating erythrocytes were studied in a subgroup of 4 ALS patients and 8 controls. Both impaired glucose tolerance and diabetes mellitus were evenly distributed between the study groups, and no difference in mean blood glucose levels during the OGTT was found between ALS and control patients. Fasting plasma immunoreactive insulin concentration was significantly higher in ALS patients as compared to controls, but plasma IRI increments to the glycemic stimulus were similar in the 2 groups. The number of insulin binding sites per cell appeared lower in patients with ALS, but the difference in receptor concentration was not statistically significant. In addition, the specific bound fraction of 125I-insulin showed no difference between ALS and control patients. In conclusion, we were unable to demonstrate any marked deterioration of glucose tolerance or increase in insulin resistance in patients with ALS.
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PMID:Glucose tolerance in amyotrophic lateral sclerosis. 651 95

Environmental toxins may be risk factors for some forms of diabetes mellitus and neurodegenerative diseases. The medicinal and food use of seed from the cycad plant (Cycas spp.), which contains the genotoxin cycasin, is a proposed etiological factor for amyotrophic lateral sclerosis/Parkinsonism-dementia complex (ALS/PDC), a prototypical neurodegenerative disease found in the western Pacific. Patients with ALS/PDC have a very high prevalence of glucose intolerance and diabetes mellitus (in the range of 50-80%). We investigated whether the cycad plant toxin cycasin (methylazoxymethanol (MAM) beta-D-glucoside) or the aglycone MAM are toxic in vitro to mouse or human pancreatic islets of Langerhans. Mouse pancreatic islets treated for 6 days with cycasin impaired the beta-cell insulin response to glucose, but this effect was reversible after a further 4 days in culture without the toxin. When mouse islets were exposed for 24 hr to MAM/MAM acetate (MAMOAc; 0.1-1.0 mM), there was a dose-dependent impairment in insulin release and glucose metabolism, and a significant decrease in islet insulin and DNA content. At higher MAM/MAMOAc concentrations (1.0 mM), widespread islet cell destruction was observed. Glucose-induced insulin release remained impaired even after removal of MAM and a further culturing for 4 days without the toxin. MAM damages islets by two possible mechanisms: (a) nitric oxide generation, as judged by increased medium nitrite accumulation; and (b) DNA alkylation, as judged by increased levels of O6-methyldeoxyguanosine in cellular DNA. Incubation of mouse islets with hemin (10 or 100 microM), a nitric oxide scavenger, or nicotinamide (5-20 mM) protected beta-cells from a decrease in glucose oxidation by MAM. In separate studies, a 24 hr treatment of human beta-islet cells with MAMOAc (1.0 mM) produced a significant decrease in both insulin content and release in response to glucose. In conclusion, the present data indicate that cycasin and its aglycone MAM impair both rodent and human beta-cell function which may lead to the death of pancreatic islet cells. These data suggest that a "slow toxin" may be a common aetiological factor for both diabetes mellitus and neurodegenerative disease.
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PMID:Cycad toxin-induced damage of rodent and human pancreatic beta-cells. 764 37

The clinical relevance of neurological disorders associated with impaired glucose tolerance(IGT) is reviewed. In this review some neurological diseases, such as, myotonic dystrophy, Crow-Fukase syndrome, Wolfram syndrome (DIDMOAD), Friedreich ataxia, spinal muscular atrophy of the Kennedy-Alter-Sung type, amyotrophic lateral sclerosis, Parkinson-dementia, and MELAS are discussed in relation to, glucose intolerance. Although the etiology of these disorders still remains an enigma, MELAS was caused by an A-to-G mutation at nucleotide position 3243 of the mitochondria genome. An association of "diabetic neuropathy" with IGT appears to be negative. Peripheral nerve function did not differ between IGT and control subjects, whereas autonomic nerve function deviated; an abnormal expiration to inspiration ratio of R-R interval was significantly more common in IGT than in control subjects. In conclusion, diabetes, but not IGT, is associated with peripheral nerve dysfunction.
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PMID:[Neurological disorders associated with impaired glucose tolerance]. 891 31

Outbred CD-1 mice carry a spectrum of genetic susceptibilities for obesity and type 2 diabetes. ALS is an inbred strain with low antioxidant defenses produced by inbreeding CD-1 mice, with selection for susceptibility to alloxan, a generator of highly reactive oxygen free radicals and a potent beta-cell toxin. The objective of this study was to determine if the low ability to diffuse free radical stress would contribute to spontaneous type 2 diabetes development in alloxan-untreated males. Indeed, both hyperinsulinemia and impaired glucose tolerance developed spontaneously between 6 and 8 weeks of age in alloxan-untreated males. Further aging was accompanied by increases in body mass, progressively more severe hyperinsulinemia, and development of overt hyperglycemia. Transition from impaired glucose tolerance to overt hyperglycemia correlated with a decreased ratio of reduced to oxidized glutathione. Evidence that the increased oxidative burden elicited the type 2 diabetes syndrome was obtained by the systemic elevation of the antioxidative capacity through daily administration of R-lipoic acid. R-lipoic acid (30 mg/kg) prevented hyperglycemia, reduced insulin levels, and increased free radical scavenging potential. This mouse model with reduced ability to diffuse free radical stress is of obvious interest because free radical-mediated damage is implicated in the pathogenesis and complications of both type 1 and type 2 diabetes.
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PMID:ALS/Lt: a new type 2 diabetes mouse model associated with low free radical scavenging potential. 1474 77

Both epidemiological and experimental studies have shown that impaired growth in utero due to maternal malnutrition, resulting in low birth weight, is associated with a high incidence of glucose intolerance, insulin resistance, and type 2 diabetes in adult life. Maternal malnutrition is a worldwide problem and unavoidable; therefore, prevention of type 2 diabetes in low birth weight infants who reach adulthood is difficult to achieve. Administration of human umbilical cord blood (HUCB) mononuclear cells into type 1 and type 2 diabetic mice has been shown to improve both their blood glucose levels and survival. It has also been shown that the progenitor cells derived from HUCB improve not only glycemia but also other disease conditions, including systemic lupus erythematosis, amyotrophic lateral sclerosis, Alzheimer's disease, stroke, brain damage in animals and certain malignancies in humans. Transfusion of unrelated HUCB, although abundantly available, is underutilized as a therapeutic agent. Therefore, we propose the hypothesis that transfusion of HUCB to low birth weight infants be considered a therapeutic modality to prevent the development of type 2 diabetes in their adulthood.
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PMID:Administration of human umbilical cord blood to low birth weight infants may prevent the subsequent development of type 2 diabetes. 1648 Nov 20

Our objectives were to analyse carbohydrate metabolism in a series of ALS patients and to examine potential association with parameters of lipid metabolism and clinical features. Glucose tolerance was assessed by the oral glucose tolerance test in 21 non-diabetic ALS patients and compared with 21 age- and sex-matched normal subjects. Lipids and lactate/pyruvate ratio, levels of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-6) and adipocytokines (leptin and adiponectin) were also measured in ALS patients. Mann-Whitney U-tests analysed continuous data and Fisher's exact tests assessed categorical data. Blood glucose determined 120 min after the glucose bolus was significantly higher in patients with ALS (7.41 mmol/l+/-1.68) compared to controls (6.05+/-1.44, p=0.006). ALS patients with impaired glucose tolerance (IGT) according to WHO criteria (n=7, 33%) were more likely to have elevated free fatty acids (FFA) levels compared to patients with normal glucose tolerance (0.77 nmol/l+/-0.30 vs. 0.57+/-0.19, p=0.04). IGT was not associated with disease duration or severity. In conclusion, patients with ALS show abnormal glucose tolerance that could be associated with increased FFA levels, a key determinant of insulin resistance. The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation.
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PMID:Impaired glucose tolerance in patients with amyotrophic lateral sclerosis. 2018 18

Malnutrition and dehydration are common and result from swallowing disorders secondary to degeneration of brainstem motor neurons. Recent knowledge argues in favor of the associated primary metabolism abnormalities. Though muscle atrophy, a paradoxical hypermetabolism at rest has often been observed. Hyperlipidemia and glucose intolerance are more frequent than in general population. The heterogeneity of the nutritional assessment of patients in published series is due, partially at least, to the use of disparate criteria and evaluating procedures. Weight lost is an independent negative survival prognostic factor. Overweight may be beneficial for the survival of ALS patients. A specific nutritional management for ALS is an essential point in the multidisciplinary support. The criteria leading to artificial nutrition indication are medical, mainly based on percentage of weight loss, but also psychological and ethical.
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PMID:[Nutritional management in amyotrophic lateral sclerosis: A medical and ethical stake]. 2213 88


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