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)

Carnitine metabolism and the therapeutic use of carnitine has been a major area of interest in dialysis patients. The purpose of this study was to determine whether any correlations exist between carnitine status and selected clinical parameters in hemodialysis (HD) patients. This study was an observational study of data from patients receiving HD at a Midwest dialysis center. The subjects (n=49) were 60+/-16 (mean+/-SD) years of age and 48% male. Fifteen percent of the subjects had type 1 diabetes mellitus (DM), 29% had type 2 DM, and 25% had left ventricular hypertrophy (LVH). The serum-free and total carnitine, and acylcarnitine concentrations were: 40.3+11.8 microm/l, 22.8+/-7.3, and 17.5+/-5.9 microm/l, respectively. The serum acylcarnitine to free carnitine ratio (A/F) was 0.80+/-0.27. Blood urea nitrogen (BUN), parathyroid hormone and ejection fraction were positively correlated and age and left atrial dilation (cm) were negatively correlated with serum total carnitine (P<0.05). BUN and hematocrit were positively correlated (P<0.05) and age was negatively correlated with free carnitine. Subjects who used mannitol or were male had significantly higher concentrations of both free and total carnitine, respectively (P<0.05). Subjects using aspirin had lower concentrations of serum total carnitine (P<0.10). These results suggest certain subgroups of patients may need to be targeted for further studies with carnitine replacement therapy, i.e. long-term patients, older patients, patients with left verticular hypertrophy and left atrial enlargement, females and patients on aspirin therapy.
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PMID:Serum carnitine concentrations correlated to clinical outcome parameters in chronic hemodialysis patients. 1475 90

Carnitine is essential for the lipid and carbohydrate metabolism, and proper metabolic control in type 1 diabetes has potential impact on long-term complications. The plasma total, free, and acylcarnitine levels in 47 children and adolescents with type 1 diabetes were determined by a radioisotopic assay and compared to the values of a series of anthropometric measurements and metabolic parameters, including blood glycosylated hemoglobin Alc, serum cholesterol and triglycerides, and urine microalbumin levels. Plasma values for total, free, and acylcarnitine were 30.1+/-7.26, 20.0+/-4.50, and 10.2+/-6.47 micromol/l, respectively. Acyl/free carnitine ratio was 0.544+/-0.369. Individuals with type 1 diabetes had significantly lower total and free carnitine levels and significantly higher acyl/free carnitine ratios than controls (P<.001). Plasma total and free carnitine levels were inversely correlated to the duration of diabetes (P=.036 and P=.071, respectively). No statistical relationship was documented between carnitine levels and the remaining anthropometric and metabolic variables. In conclusion, total and free carnitine levels are decreased in children and adolescents with type 1 diabetes. This reduction is time related and may have potential interactions with the long-term complications of type 1 diabetes. Larger studies are required for final conclusions to be drawn on the precise role of carnitine and the possible benefit, if any, of carnitine supplementation in diabetic patients.
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PMID:Carnitine deficiency in children and adolescents with type 1 diabetes. 1533

Diabetic polyneuropathy (DPN) is the most common late complication of diabetes mellitus. The underlying pathogenesis is multifaceted, with partly interrelated mechanisms that display a dynamic course. The mechanisms underlying DPN in type 1 and type 2 diabetes mellitus show overlaps or may differ. The differences are mainly due to insulin deficiency in type 1 diabetes which exacerbates the abnormalities caused by hyperglycaemia. Experimental DPN in rat models have identified early metabolic abnormalities with consequences for nerve conduction velocities and endoneurial blood flow. When corrected, the early functional deficits are usually normalised. On the other hand, if not corrected, they lead to abnormalities in lipid peroxidation and expression of neurotrophic factors which in turn result in axonal, nodal and paranodal degenerative changes with worsening of nerve function. As the structural changes progress, they become increasingly less amendable to metabolic interventions. In the past several years, experimental drugs--such as aldose reductase inhibitors, antioxidants and protein kinase C inhibitors--have undergone clinical trials, with disappointing outcomes. These drugs, targeting a single underlying pathogenetic factor, have in most cases been initiated at the advanced stage of DPN. In contrast, substitution of acetyl-L-carnitine (ALC) or C-peptide in type 1 DPN target a multitude of underlying mechanisms and are therefore more likely to be effective on a broader spectrum of the underlying pathogenesis. Clinical trials utilising ALC have shown beneficial effects on nerve conduction slowing, neuropathic pain, axonal degenerative changes and nerve fibre regeneration, despite relatively late initiation in the natural history of DPN. Owing to the good safety profile of ALC, early initiation of ALC therapy would be justified, with potentially greater benefits.
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PMID:Acetyl-L-carnitine in diabetic polyneuropathy: experimental and clinical data. 1769 89

Diabetic neuropathy and its underlying pathogenesis are reviewed. It has been documented for some time that diabetic neuropathy differs in both human and experimental type 1 versus type 2 diabetes. Such differences are accounted for by impaired insulin action and signal transduction in type 1 diabetes, whereas hyperglycemia per se contributes equally to neuropathy in the two types of diabetes. Such differences in basic initiating factors and pathogenesis translate into differences in the functional and structural expressions of neuropathy in type 1 and type 2 diabetes. Type 1 neuropathy shows a more rapid progression with more severe functional and structural changes. Several experimental mono-therapies have been tested over the last decades which unfortunately have not been efficacious. Therefore discrepancies in underlying pathogenetic mechanisms in the two types of diabetic neuropathy will have to be taken into account in the design of future therapies, which should target several key pathogenetic mechanisms. Therapies that meet these criteria include replacement of acetyl-L-carnitine and replenishment of C-peptide in type 1 diabetic neuropathy.
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PMID:The heterogeneity of diabetic neuropathy. 1850 46

Carnitine (2-hydroxy-4-trimethylammonium butyrate, vitamin BT) is a small hydrophilic molecule derived from protein-bound lysine, not degraded in the body but excreted via urine, bile and breast milk. Carnitine stimulates the catabolism of long-chain fatty acids (FAs), by transporting them to mitochondria for oxidation, and the intracellular decomposition of branched-chain ketoacids. It also helps to excrete toxic exogenous and nontoxic endogenous organic acids via urine. It further participates in the production of pulmonary surfactant, inhibits free radicals production and demonstrates other antioxidant properties. After delivery, infants dramatically increase energy demands for movement, growth, differentiation and maintenance of the body temperature that strongly depend on FAs oxidation which is facilitated by carnitine. At early stages of life, carnitine biosynthesis is less efficient than in adults and immature infants have less carnitine tissue reserves than term infants. Carnitine supplementation is recommended in newborns with aciduria, childhood epilepsy associated with valproate-induced hepatotoxicity, in kidney-associated syndromes, and premature infants receiving total parenteral nutrition. Concentrations of carnitine and acylcarnitines in neonatal blood have been postulated a useful tool for the diagnosis of type 1 diabetes, as well as the detection and monitoring of many inherited and acquired metabolic disorders. Taking into account the complex metabolic role of cellular FAs transporters, further studies are needed on indications and contraindications for carnitine supplementation in different clinical settings during early developmental period.
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PMID:The role of carnitine in the perinatal period. 2587 78