UMLS:C0011849 - FACTA Search

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Query: UMLS:C0011849 (diabetes)
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The diagnosis of mitochondrial myopathy depends upon a constellation of findings, family history, type of muscle involvement, specific laboratory abnormalities, and the results of histological, pathobiochemical and genetic analysis. In the present paper, the authors describe the diagnostic approach to mitochondrial myopathies manifesting as extraocular muscle disease. The most common ocular manifestation of mitochondrial myopathy is progressive external ophthalmoplegia (PEO). To exclude myasthenia gravis, ocular myositis, thyroid associated orbitopathy, oculopharyngeal muscular dystrophy, and congenital fibrosis of the extraocular muscles in patients with an early onset or long-lasting very slowly progressive ptosis and external ophthalmoplegia, almost without any diplopia, and normal to mildly elevated serum creatine kinase and lactate, electromyography, nerve conduction studies and MRI of the orbits should be performed. A PEO phenotype forces one to look comprehensively for other multisystemic mitochondrial features (e.g., exercise induced weakness, encephalopathy, polyneuropathy, diabetes, heart disease). Thereafter, and presently even in familiar PEO, a diagnostic muscle biopsy should be taken. Histological and ultrastructural hallmarks are mitochondrial proliferations and structural abnormalities, lipid storage, ragged-red fibers, or cytochrome-C negative myofibers. In addition, Southern blotting may reveal the common deletion, or molecular analysis may verify specific mutations of distinct mitochondrial or nuclear genes.
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PMID:Extraocular mitochondrial myopathies and their differential diagnoses. 1676 Jan 17

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1-2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease.
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PMID:Who should receive a statin these days? Lessons from recent clinical trials. 1696 68

Interleukin-6 (IL-6) is associated with many disease states in humans. We prospectively sought to determine whether IL-6 levels increased following percutaneous coronary intervention (PCI) in the absence of myonecrosis. Additionally, we systematically assessed other clinical and anatomic factors associated with IL-6 levels in a population of patients with coronary atherosclerosis undergoing PCI. Blood samples were collected from 117 patients at baseline, 8 and 16 h following PCI. Samples were assayed for IL-6, creatine kinase-myocardial band (CK-MB), troponin-I (Tn-I), high sensitivity C-reactive protein, glucose, haemoglobin A1c, and a lipid profile. Genotyping of the -174G-->C polymorphism of the IL-6 gene was performed. IL-6 levels increased following PCI among the study group (slope = 0.4 pg/mL/h, P = 0.001). IL-6 levels increased to a similar degree in the absence of myonecrosis. Patients with the XC genotype (either having the GC or the CC allele) had higher IL-6-values at baseline compared to GG genotype patients (4.9 +/- 6.4 vs. 2.6 +/- 1.8 pg/mL, P = 0.02). Multivariable predictors of detectable baseline IL-6 levels included XC genotype (odds ratio [OR]: 4.14, 95% CI 1.58-10.82, P = 0.004), ACC/AHA type C lesion classification (OR: 4.08, 95% CI 1.54-10.84, P = 0.005), elevated baseline Tn-I (OR: 3.31, 95% CI 1.16-9.43, P = 0.025), diabetes (OR: 3.00, 95% CI 1.11-8.09, P = 0.030), and waist circumference (OR: 1.49, 95% CI 1.08-2.06, P = 0.015). Predictors of peak IL-6 following PCI included the XC genotype (estimate 1.4, 95% CI 1.06-1.87, P = 0.019), homeostasis model assessment (estimate 0.99, 95% 0.982-0.999, P = 0.042) and baseline Tn-I > upper limit of normal (estimate 0.7, 95% CI 0.50-0.96, P = 0.039). Lastly, IL-6 increased following PCI even in the absence of myonecrosis as measured by Tn-I elevation. IL-6 levels are also related to the -174G-->C polymorphism, arterial injury, lesion complexity, and insulin resistance.
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PMID:Increase in interleukin-6 following arterial injury is related to insulin resistance, the -174G-->C polymorphism and complex plaque morphology. 1698 79

Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus) is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion) varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.
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PMID:Creatine kinase activity in patients with diabetes mellitus type I and type II. 1699 40

An analysis is made of the effect of alternateday dosing of atorvastatin and standard once-daily dosing, based on mean low-density lipoprotein (LDL) reduction from baseline in type 2 diabetics. Forty-four type 2 diabetics were enrolled in the study. In compliance with American Diabetes Association (ADA) and National Cholesterol Education Program Expert Panel (NCEP-III) guidelines, LDL-C<100 mg/dl was chosen as the treatment target. Patients were assigned to 10 mg atorvastatin as an initial dose every day. The atorvastatin dose was doubled every 6 weeks if the patients failed to reach the treatment target. After achieving LDL<100 mg/dl, the patients were assigned to the corresponding atorvastatin dose every other day for 12 weeks. Thirty-three patients correctly completed the study. LDL-C decreased 39% after the every-day period and 23% after the alternate-day atorvastatin dosing period (p<0.05). The target LDL-C concentration of <100 mg/dl was maintained in 19 patients (57.6%) in the alternate-day period. None of the 33 patients showed elevations in liver enzymes or creatine kinase during the alternate-day dosing period. Alternate-day dosing of atorvastatin could be an effective and safe alternative to daily-dosing in some type 2 diabetic patients.
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PMID:Alternate-day dosing of atorvastatin: effects in treating type 2 diabetic patients with dyslipidaemia. 1714 84

Protein glycation has been implicated in the aging process as well as the complications of diabetes (retinopathy, neuropathy, nephropathy, and atherosclerosis). The nitrogen substituents of Lys, Arg, and His residues and the N-terminus of proteins are known to be readily glycated. As the thiol group of Cys is a powerful nucleophile, we hypothesized that Cys residues should also be targets of glycation and that low molecular mass thiols may act as protective agents. In this study the role of thiol glycation, induced by dicarbonyls, in protein cross-link formation and damage prevention is examined. It is shown that incubation of creatine kinase with glyoxal results in protein cross-link formation, with this occurring concurrently with loss of thiol groups, enzyme inactivation, and formation of S-carboxymethylcysteine, a product of glyoxal adduction to Cys residues. Cross-links have also been detected between N-acetylcysteine and the Lys-rich protein histone H1, demonstrating the formation of thiol-glyoxal-amine cross-links. Mass spectrometry has been used to characterize some of these cross-links as 2-(alkylthio)acetamides. A range of low molecular mass thiols have been shown to inhibit dicarbonyl adduction to, and cross-linking of, the thiol-free protein lysozyme, consistent with these thiols being alternative (sacrificial) targets of glycation. Some of these thiols are more efficient modulators of glycation than established glycation inhibitors such as aminoguanidine. These data demonstrate that thiols are facile targets of glycation and that low molecular mass thiols are potent glycation inhibitors. These data may aid the design of therapeutic agents for the treatment of the complications of diabetes.
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PMID:Protein and low molecular mass thiols as targets and inhibitors of glycation reactions. 1717 81

Left ventricular apical ballooning syndrome (LVABS) is a clinical condition that may mimic ST-elevation acute myocardial infarction (AMI). To assess incidence, clinical findings, and outcome of white women with LVABS, we reviewed 305 consecutive women with chest pain and anterior ST-elevation AMI referred for potential mechanical revascularization; 36 (12%) patients met the diagnostic criteria for LVABS and were compared with the remaining 269 women with angiographic evidence of coronary artery disease (CAD). Patients with LVABS showed a lower incidence of diabetes mellitus (5% vs 21%, p = 0.023), a higher rate of antecedent stressful events (26% vs 3%, p <0.0001), and a higher heart rate at admission (91 +/- 20 vs 82 +/- 19, p = 0.018) than women with CAD. Urgent angiography showed no significant CAD in patients with LVABS and an average of 1.6 +/- 0.7 diseased coronary arteries (>50% stenosis) in the 269 control women (p = 0.0001). Peak creatine kinase-MB value was lower in patients with LVABS (21 +/- 26 mU/ml) than in women with CAD (307 +/- 302 mU/ml, p = 0.0001). The only independent predictors of LVABS among women with anterior AMI were peak creatine kinase-MB value (p = 0.0001) and the presence of an antecedent stressful event (p = 0.001). LV systolic function at admission was similar between women with LVABS and those with CAD (echocardiographic ejection fraction 35.6 +/- 8.4% vs 35.5 +/- 8.0%, p = 0.944) but was significantly different at discharge (ejection fraction 50.1 +/- 9.6% vs 45.2 +/- 13.5%, p = 0.021). Moreover, at 6-month follow-up, women with LVABS showed a better survival rate (97% vs 86%, p = 0.055) and freedom from major cardiac events (death, reinfarction, or rehospitalization 92% vs 69%, p = 0.001) than women with CAD. In conclusion, few women presenting with clinical features of anterior AMI have LVABS. Despite a favorable outcome, LVABS should be considered in the differential diagnosis of women with chest pain and ST-segment elevation in the precordial leads. Peak creatine kinase-MB value and the presence of an antecedent stressful event are strong predictors of LVABS in women with anterior AMI.
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PMID:Incidence, clinical findings, and outcome of women with left ventricular apical ballooning syndrome. 1722 15

Ischemic heart disease in diabetic patients might be linked to the accumulation of advanced-glycation end products (AGEs). In ischemic rat hearts, expression of receptor for AGEs and its ligands is significantly enhanced and involved in cardiac ischemia/reperfusion (I/R) injury even in the absence of diabetes. It has recently been reported that diabetic human myocardium cannot be protected by preconditioning. In this context, our hypothesis was that beta1-adrenergic preconditioning might be altered in the presence of AGEs. Using an isolated non-working rat heart model, this study investigated the effect of AGEs on cardioprotection induced by transient beta1-adrenoceptor (beta1-AR) stimulation with xamoterol (Xa). After 6-hydroxydopamine (6-OHDA) pre-treatment and a 20-min stabilization period, hearts were perfused at constant pressure for 20 min, then subjected to 40 min of global ischemia and 30 min of reperfusion (I/R, Ctrl); and exposed to 0.01 microm Xa for 5 min framed with or without 15.2 microm albumin (Alb) or glycated albumin (Gly Alb). The main endpoints were the mean coronary flow (MCF), the left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and creatine kinase (CK) release and necrosis area. XA induced an increase in the MCF after I/R (t = 85 min), a protective effect on the LVEDP, an improvement in RPP, a decrease of CK release during reperfusion and a reduction of necrotic area. The beneficial effects induced by Xa during reperfusion were suppressed by the administration of Gly Alb during Xa infusion, whereas Alb did not hamper Xa-induced protection. These results suggest that AGEs suppress the cardioprotection resulting from the activation of beta1-ARs and thus might contribute to cardiovascular damages seen in diabetic patients.
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PMID:Advanced-glycation end products (AGEs) derived from glycated albumin suppress early beta1-adrenergic preconditioning. 1722 43

The authors report a case with life-threatening hyperglycemia and acidosis in a patient with no previous diabetic history following treatment with olanzapine. A 35-year-old woman with a history of bipolar affective disorder treated with olanzapine presented with severe diabetic ketoacidosis. She had no prior history of diabetes or risk factors for diabetes. Glycosylated hemoglobin (HbA1c) on admission blood sample suggested that long-term glycemic control had been poor. The authors postulate that treatment with olanzapine precipitated hyperglycemia, an elevated creatine kinase level, and a high amylase level. A concurrent urinary tract infection precipitated an episode of sepsis, which combined to precipitate life-threatening diabetic ketoacidosis. During her stay in the intensive treatment unit and subsequently in the medical ward, her blood glucose concentration was intensively monitored. She remains on insulin therapy, and her antipsychotic medication was changed to risperidone. Newer atypical antipsychotic drugs such as olanzapine have been introduced with the benefit of fewer extrapyramidal side effects. A number of these have reported metabolic side effects of uncertain etiology such as diabetic ketoacidosis and elevated creatine kinase. The authors believe that the diabetic ketoacidosis occurred in this patient, who had no previous history of diabetes mellitus. Blood glucose should be monitored in patients taking olanzapine, especially in those patients with risk factors for diabetes mellitus.
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PMID:Life-threatening hyperglycemia and acidosis related to olanzapine: a case report and review of the literature. 1725 69

Myocyte necrosis has been considered to play a fundamental role in the pathophysiology of congestive heart failure (CHF), which has usually evolved as a consequence of depletion of compensatory mechanisms and contractile reserve of myocardium. Elevated levels of creatine kinase MB (CK-MB) and troponin I (Tn-I) have been regarded as biochemical markers of myocyte necrosis. This study was planned to investigate the specificity and sensitivity of Tn-I and CK-MB in CHF and to examine the correlation of these markers with disease severity. A total of 104 patients (38 female, 66 male; mean age, 66 y [range, 36-89]) with symptoms and signs of heart failure on admission and with a reduced left ventricular ejection fraction (EF; by transthoracic echocardiography) were labeled "the patient group," and 58 patients (40 female,18 male; mean age, 61 y [range, 34-77]) with no signs or symptoms of CHF and with a normal EF detected by transthoracic echocardiography were included in the study as "the control group." Left ventricular EFs, end-diastolic diameters, and end-systolic diameters of patients in both groups were measured. Blood samples were drawn from all patients in both groups on admission, so that levels of CK-MB and Tn-I could be measured. All patients in both groups also underwent coronary angiography. Conditions leading to elevation of CK-MB or Tn-I were considered exclusion criteria. The 2 groups failed to show any significant differences in terms of mean age and the presence of coronary artery disease, hypertension, or diabetes mellitus (P>.05). Mean EF in the patient group was lower than that in the control group (P<.05). Mean CK-MB and Tn-I in the patient group were significantly higher than in the control group (P<.05). In the patient group, hypertensive patients were found to have significantly higher mean values of CK-MB than were seen in normotensive patients in the same group (P<.05). In the patient group, 52 cases were considered to be class I-II (New York Heart Association [NYHA]) (group 1), and 52 were considered to be class III-IV (group 2). Group 1, group 2, and the control group did not differ significantly from one another with regard to the presence of coronary artery disease, hypertension, and diabetes mellitus (P>.05). The mean EF in group 2 was significantly lower than that in group 1 and in the control group (P<.05); the mean EF in group 1 was significantly lower than that in the control group (P<.05). Group 1 values did not differ significantly from those of group 2 or the control group in terms of enzymatic markers (P>.05), but group 2 had significantly higher mean values of CK-MB and Tn-I than were noted in the control group (P<.05). The uphill course of CK-MB and Tn-I values from the control group to group 2 (NYHA class III-IV) was statistically significant (P<.05). Serum concentrations of CK-MB and Tn-I may become elevated in severely symptomatic patients with CHF (particularly NYHA class III-IV), demonstrating a relationship between clinical severity of the disease and elevation of myocardial enzymes (CK-MB and Tn-I).
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PMID:Clinical importance of elevated CK-MB and troponin I levels in congestive heart failure. 1727 73

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