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)

It has been generally accepted that acidosis results in hyperkalemia because of shifts of potassium from the intracellular to the extracellular compartment. There is ample clinical and experimental evidence, however, to support the conclusion that uncomplicated organic acidemias do not produce hyperkalemia. In acidosis associated with mineral acids (respiratory acidosis, end-stage uremic acidosis, NH4Cl-or CaCl2-induced acidosis), acidemia per se, results in predictable increases in serum potassium concentration. In acidosis associated with nonmineral organic acids (diabetic and alcoholic acidosis, lactic acidosis, methanol and the less common forms of organic acidemias secondary to methylmalonic and isovaleric acids, and ethylene glycol, paraldehyde and salicylate intoxications), serum potassium concentration usually remains within the normal range in uncomplicated cases. A number of factors, however, may be responsible for hyperkalemia in some of these patients other than the acidemia per se. These include dehydration and renal hypoperfusion, preexisting renal disease, hypercatabolism, diabetes mellitus, hypoaldosteronism, the status of potassium balance, and therapy. The mechanism(s) of this differing effect of mineral and organic acidemias on transmembrane movement of potassium remains undefined. The prevalent hypothesis, however, favors the free penetrance of the organic anion into cells without creating a gradient for the hydrogen ions and, thus, obviating the efflux of intracellular potassium. The importance of the presence of hyperkalemia in clinical states of organic acidemias is obvious. A search for the complicating factors reviewed above should be undertaken since organic acidemias per se, should not be expected to be accompanied by elevations of serum potassium concentration. Moreover, the classical teaching that the absence of hyperkalemia during severe acidosis is indicative of severe potassium deficiency, may not be universally valid in patients with uncomplicated organic acidemias.
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PMID:Serum potassium concentration in acidemic states. 679 Oct 40

The combined glucose and lactate values in vitreous humour were examined in 52 autopsy cases without diabetes and 10 cases with diabetes, and the significance thresholds for the distribution of the combined values were calculated. The use of these values in the diagnosis of antemortem hyperglycaemia, lactic acidosis or hypoglycaemia is discussed.
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PMID:Combined glucose and lactate values in vitreous humour for postmortem diagnosis of diabetes mellitus. 707 64

Four patients with severe lactic acidosis associated with septic shock were treated with sodium dichloroacetate (DCA) (50 mg/kg body wt), an activator of pyruvate dehydrogenase. All patients were in a group with an expected mortality rate of 90-100%, based on previous studies. In one patient, treatment with DCA was associated with a decrease in blood lactate levels from 11.2 mM before treatment to 0.8 mM 16 h later. Markedly elevated blood pyruvate and alanine levels also decreased to normal. After treatment, the arterial blood pH rose to 7.53, and vasopressor agents were no longer needed to support blood pressure. Some degree of biochemical improvement was also noted in the other cases in whom the blood lactate levels before treatment were 15, 17, and 31 mM. However, all three patients eventually died of refractory acidosis.
Diabetes Care
PMID:Treatment of severe lactic acidosis with dichloroacetate. 715 55

In this review the actual stage of knowledge is mediated concerning the oral therapy of diabetes mellitus by biguanides. After a historical review the pharmacological data obtained by animal experiments as well as by clinical application are summarized and the effects and side-effects are derived. The problem of lactic acidosis and the controversial discussion due to the UGDP-study concerning the relation of the biguanides to the cardiovascular system are largely discussed. Concrete recommendations are given concerning the clinical practice by means of the communication of the revised indications and contraindications of the therapy with biguanides.
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PMID:[Indications and contraindications of biguanide therapy in diabetes mellitus]. 722 45

After a brief survey of the mechanism of biquanides treatment and their indications and contraindications with the peroral treatment of diabetes mellitus, the adverse effects of that treatment are stressed upon, manifested mainly in lactacidosis. The latter is indicated to be most frequently found during the treatment with tenformin, rarely -- with buformin and most rarely and in a lighter form -- with metformin. That uneven effect of biquanide preparations is associated with a certain difference in their pharmacodynamics and pharmacokinetics. On the other hand -- those adverse effects result most frequently from unproper treatment carried outnot observing the indications and particularly the contraindications and surpassing the therapeutic doses. Very good results are reported, that were obtained by the authors, in the treatment with metform of 70 diabetic patients with insulin-independent type of diabetes and body overweight, that failed to respond to the treatment with a reducing diet or a diet and sulfurea preparations and resistant to insulin. Indications for that treatment are presented as well as the necessity of strict observation of the contraindications for its administration.
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PMID:[Treatment of diabetics with metformin]. 741 55

The A 3243 G mutation of the mitochondrial tRNA(Leu) gene was found to segregate with maternally inherited diabetes mellitus, sensorineural deafness, hypertrophic cardiomyopathy, or renal failure in a large pedigree of 35 affected members in four generations. Presenting symptoms almost consistently involved deafness and recurrent attacks of migraine-like headaches, but the clinical course of the disease varied within and across generations. The A 3243 G mutation has been previously reported in association with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome (MELAS) and with diabetes mellitus and deafness. To our knowledge, however, hypertrophic cardiomyopathy is not a common feature in people with the A 3243 G mutation and renal failure has not been hitherto reported in association with this mutation. The present observation gives additional support to the variable clinical expression of mtDNA mutations in humans.
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PMID:Point mutation of the mitochondrial tRNA(Leu) gene (A 3243 G) in maternally inherited hypertrophic cardiomyopathy, diabetes mellitus, renal failure, and sensorineural deafness. 747 62

MELAS syndrome is a form of mitochondrial myopathy with manifestations of seizure, stroke-like syndrome, lactic acidosis, ragged red muscle fibres and mitochondrial encephalopathy. The syndrome has been reported in association with a variety of endocrine and metabolic disorders including diabetes mellitus (DM), hypothalamo-pituitary hypofunction, hypothalamic growth hormone deficiency and delayed puberty. Mitochondrial DNA (mtDNA) point mutation may be the major pathological defect. However, association of MELAS syndrome with hyperthyroidism has not previously been reported. A case is reported from Taiwan of a 32-year-old woman suffering from MELAS syndrome with associated DM and hyperthyroidism. When the latter was diagnosed in April 1988, the patient underwent subtotal thyroidectomy. There was no family history of thyroid disease. Because of repeated seizures, she had computed tomography (CT) and magnetic resonance imaging (MRI) of the brain which showed focal, low-density lesions over the cerebral hemispheres. Both serum and cerebral spinal fluid lactic acid levels were elevated. Mild elevations of serum T4 and T3 and a high titre of TSH receptor antibody were still present. Hyperglycaemia was noted during hospitalization and DM confirmed by oral glucose tolerance test. Muscle biopsy showed ragged red fibres. DNA analysis showed an A-to-G transition at the 3243rd nucleotide position of the tRNA(Leu(UUR)) gene of the mtDNA from the patient. Quantitative polymerase chain reaction (PCR) and restriction analysis revealed that about 60% of the blood mtDNA was of mutant type. The patient received antithyroid drugs for hyperthyroidism, diet control for DM and anti-epileptic drugs for seizure.
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PMID:MELAS syndrome associated with diabetes mellitus and hyperthyroidism: a case report from Taiwan. 755 21

An A to G transition at nucleotide 3,243 in the tRNA(Leu(UUR)) gene of mitochondrial DNA (mtDNA) has been suggested to be the disease-related mutation for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Recently, the same mutation has also been found in several pedigrees with maternally inherited diabetes mellitus and sensorineural deafness. We report here a family showing the association of deafness and diabetes mellitus, as the predominant clinical features, with this mutation. The mutation was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA, in two generations. In this family, it is noteworthy that two members with the mutation had some symptoms of MELAS such as short stature, seizures and mental retardation and that one had no clinical symptoms though the mtDNA mutation was identified in his blood. The findings in this family demonstrate the diversity of clinical expression of the mtDNA mutation and suggest that a combination of sensorineural deafness and diabetes mellitus is only one typical presentation of the various phenotypic features caused by the 3,243 mutation.
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PMID:[Detection of a mutation in mitochondrial DNA in a family with sensorineural deafness and diabetes mellitus as the predominant clinical features]. 756 31

The mitochondrial tRNALeu(UUR) A-->G(3243) mutation was identified in 22 unrelated patients. The probands and their relatives were assessed clinically and by quantitative mitochondrial DNA (mtDNA) analysis. While 10 probands had clinical features consistent with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), usually associated with this mutation, 12 probands had other phenotypes including other encephalopathies, chronic progressive external ophthalmoplegia (CPEO), myoclonic epilepsy and ragged red fibres (MERRF), myopathy alone and diabetes and deafness. Histochemical analyses of muscle biopsies showed a higher proportion of cytochrome oxidase (COX) negative fibres, but fewer strongly COX reactive fibres, in patients with CPEO compared with those with MELAS. The proportion of mutant mtDNA present in blood was significantly greater in symptomatic than asymptomatic subjects, and was correlated with age in both. This correlation was not observed in patients with the tRNALys A-->G(8344) mutation. The proportion of mutant mtDNA A-->G(3243) in muscle was always greater than that in blood. Significant correlations between proportion of mutant mtDNA in blood and both age of onset of disease and a clinical severity score were observed. However, the proportion of mutant mtDNA in blood in affected and unaffected cases overlapped, preventing use of the genetic-clinical correlation for prognostic or predictive purposes. The presence of intrafamilial clustering of phenotypes and the imperfect relationship between proportion of mutant mtDNA and the presence or absence of disease suggests that other factors may determine the phenotype. To investigate this possibility further, the tRNALeu(UUR) gene was sequenced in 23 probands and six relatives. In 28 patients the sequence was normal apart from the 3243 mutation, but in members of one family there was a homoplasmic T-->C transition at position 3290 which was not found in 140 controls or 50 other patients with mitochondrial myopathy. The family with this transition had high levels of mutant mtDNA A-->G(3243), with a unique phenotype of predominant skeletal myopathy, suggesting that this second base change in tRNALeu(UUR) may influence the clinical phenotype.
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PMID:The mitochondrial DNA transfer RNALeu(UUR) A-->G(3243) mutation. A clinical and genetic study. 760 89

The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent used in the management of non-insulin-dependent diabetes mellitus (NIDDM). It reduces blood glucose levels, predominantly by improving hepatic and peripheral tissue sensitivity to insulin without affecting the secretion of this hormone. Metformin also appears to have potentially beneficial effects on serum lipid levels and fibrinolytic activity, although the long term clinical implications of these effects are unclear. Metformin possesses similar antihyperglycaemic efficacy to sulphonylureas in obese and nonobese patients with NIDDM. Additionally, interim data from the large multicentre United Kingdom Prospective Diabetes Study (UKPDS) indicated similar antihyperglycaemic efficacy for metformin and insulin in newly diagnosed patients with NIDDM. Unlike the sulphonylureas and insulin, however, metformin treatment is not associated with increased bodyweight. Addition of metformin to existing antidiabetic therapy confers enhanced antihyperglycaemic efficacy. This may be of particular use in improving glycaemic control in patients with NIDDM not adequately controlled with sulphonylurea monotherapy, and may serve to reduce or eliminate the need for daily insulin injections in patients with NIDDM who require this therapy. The acute, reversible gastrointestinal adverse effects seen with metformin may be minimised by administration with or after food, and by using lower dosages, increased slowly where necessary. Lactic acidosis due to metformin is rare, and the risk of this complication may be minimised by observance of prescribing precautions and contraindications intended to avoid accumulation of the drug or lactate in the body. Unlike the sulphonylureas, metformin does not cause hypoglycaemia. Thus, metformin is an effective antihyperglycaemic agent which appears to improve aberrant plasma lipid and fibrinolytic profiles associated with NIDDM. Possible long term clinical benefits of this drug with regard to cardiovascular mortality and morbidity are not yet established but are being assessed in a major ongoing study. Since metformin does not promote weight gain or hypoglycaemia it should be considered first-line pharmacotherapy in obese patients with NIDDM inadequately controlled by nonpharmacological measures. Metformin appears similarly effective for the pharmacological management of NIDDM in nonobese patients.
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PMID:Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. 760 Oct 13


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