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)

Friedreich's ataxia is an autosomal recessive neuro-degenerative disorder involving both central and peripheral nervous system. Patients also show a systemic clinical picture presenting heart disease and diabetes mellitus or glucose intolerance. The disease is caused by mutations in the FRDA gene mapped on chromosome 9q13. The product of the gene is frataxin, an 18 kDa soluble mitochondrial protein with 210 amino acids. Crystal structure suggests a new, not previously reported, protein fold. The most frequent mutation is the expansion of a GAA trinucleotide repeat located within the first intron of the gene, and represents 98% of the mutations. Point mutations are described in compound heterozygous subjects with one expanded allele. A two-step model of GAA normal alleles towards premutation alleles, which might generate further full expanded mutations in the population with Indo-European ancestry, has been postulated. Clinical phenotype is variable and an inverse correlation with the GAA expansion size has been observed. Analysis of the GAA triplet is a strong molecular tool for clinical diagnosis, genetic counselling and prenatal diagnosis. Friedreich's ataxia patho-genesis is not solved yet. Substantial data from organism models, such the S. cerevisae yeast and more recently conditioned knock-outs in mouse, and studies in heart biopsies and fibroblast cultures from patients suggest an important role of mitochondrial iron in the development of the disease. Iron is accumulated in the mitochondrial matrix of both the yeast frataxin deficient mutant and the patient fibroblasts. It has been postulated that iron-induced oxygen radical affects the oxidative phosphorylation in frataxin deficiency states favouring the disease pathology. A second hypothesis postulates a direct role of frataxin in the mitochondrial energy activation and oxidative phosphorylation. Iron chelator drugs and antioxidant drugs have been postulated for Friedreich's treatment. No results from clinical trials are available yet, but idebenone, a short-chain quinone, seems to reduce the size of hypertrophic cardiomyopathy and levels of oxidative stress molecules in patients.
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PMID:Friedreich's ataxia and frataxin: molecular genetics, evolution and pathogenesis (Review). 1135 Dec 69

Mitral annulus calcification (MAC) is best diagnosed by transthoracic echocardiography. MAC is associated with known atherosclerotic risk factors such as diabetes mellitus, hypertension and hypercholesterolemia. It is also known from the literature that patients with MAC have higher prevalence of left atrial and left ventricular enlargement, hypertrophic cardiomyopathy, atrial fibrillation, aortic valve calcification and stenosis, various cardiac conduction defects, bacterial endocarditis, cardiovascular events and stroke, though the etiological basis is unknown. Pathological studies from the 80's present a theory that MAC is a form of atherosclerosis. During the past few years we conducted a few clinical studies in order to test this theory and to examine the association between MAC and known atherosclerotic phenomena. We found higher prevalence of aortic atheroma in patients with MAC, especially complex atheroma, and we also found a continuous correlation between the MAC and atheroma thickness. We also noted that MAC patients have a higher prevalence of carotid artery stenosis, coronary artery stenosis, peripheral artery stenosis and higher levels of anti beta 2-Glycoprotein I antibodies in patients with MAC thickness equal or greater than 5 mm. These studies support the theory that MAC is a form of atherosclerosis and define a group of patients with higher prevalence of atherosclerotic disease in multiple blood vessels.
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PMID:[Association between mitral annulus calcification and atherosclerosis]. 1157 35

Friedreich's ataxia, the most common autosomal recessive inherited ataxia, is characterized by progressive gait and limb ataxia. Friedreich's ataxia is known for its occurrence within the first or second decade of life and is associated with hypertrophic cardiomyopathy, and in some cases with diabetes. Genetically, it is identified by the expression of an unstable trinucleotide GAA repeat expansion located in the first intron of the X25 gene on chromosome 9. Two brothers with very late adult-onset ataxia, and their unaffected sister, were examined for the clinical presentation of FA and for the presence of the mutated FA gene. The relationship of the expanded gene sequence to the severity of disease and age of onset were evaluated. Clinical examination revealed that the two brothers had mild ataxia and proprioceptive loss, with age of onset between 60 and 70 years of age. DNA from peripheral blood nucleated cells demonstrated a small homozygous expansion, with approximately 120-130 GAA repeats in the X25 gene in both patients. The expanded repeats were interrupted either with GAAGAG, GAAGGA, or GAAGAAAA sequences. The unaffected sister carried a normal FA genotype with 8-uninterrupted GAA repeat, observed by sequence analysis. In addition, the levels of FA gene transcript in both brothers were relatively lower than that in the unaffected sister. No detectable cardiomyopathy or diabetes was observed. Phenotypic diversity of FA is increasingly expanding. The age of onset and the structure of GAA repeat expansion plays an important role in determining the clinical features and the differential diagnosis of FA. The confirmation of the FA gene mutation in the atypical case, broadens the clinical spectrum of FA, and supports the idea that patients with even a mild form of ataxia of late adult onset should be considered for molecular testing.
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PMID:Sequence variation in GAA repeat expansions may cause differential phenotype display in Friedreich's ataxia. 1174 52

Insulin resistance and hyperinsulinemia have been observed in over 70% of the nonobese, nondiabetic subjects with essential hypertension (HT). Alpha-1 blockers, ACE-antagonists, long-acting Ca blockers including nifedipine CR, some form of beta-blockers, tilisolor, which is reported to increase blood flow, improve insulin sensitivity when blood pressure is better controlled. Decrease of serum potassium during insulin sensitivity test and intraplatelet free Ca2+ concentration is positively and negatively correlated with insulin sensitivity, respectively. Blood pressure is correlated with insulin resistance, which is also observed in secondary HT. The resistance is correlated with salt sensitivity as well as impaired nocturnal fall of blood pressure. These suggest the possible association of insulin resistance with altered intracellular cation metabolism. Insulin resistance and associated hyperinsulinemia have been observed in effort as well as vasospastic angina pectoris (VSAP), atherothrombotic cerebral infarction, and in ASO without obesity, HT, or diabetes, suggesting the resistance resulting from endothelial dysfunction. Insulin resistance has been observed in heart failure and is correlated with angiotensin II. Resistance is also observed in hypertrophic cardiomyopathy and is partially correlated with TNF-alpha. These results indicate that insulin resistance seem to be multifactorial. An effort to normalize insulin sensitivity is crucial to eliminate multiple risk factors as well as to prevent the progression of atherosclerotic vascular lesions.
J Diabetes Complications
PMID:Multifactorial insulin resistance and clinical impact in hypertension and cardiovascular diseases. 1187 61

This year the prevalence, prognosis and the cost of left ventricular function have been clarified. The significance of B natiuretic peptide has been confirmed. The influence of race on the sensitivity to different therapeutic measures has been brought up. Tobacco and diabetes appear as risk factors in cardiac insufficiency. The importance of parietal thickening regarding hypertrophic cardiomyopathy is beginning to be debated, and the risk associated with a new pregnancy in women affected by dilated cardiomyopathy of the peripartum period has been demonstrated. The significance of betablockers is confirmed, although that of angiotensin II receptor antagonists remains a source of questions, despite several advances. Endothelin receptor antagonists present divergent results. Ventricular resynchronisation advances, but its beneficial role regarding the reduction of morbidity and mortality remains to be proved.
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PMID:[The best of 2001. Heart failure]. 1190 93

Traditional health evaluations are performed while the patient is at rest. Stress echocardiography extends these examinations by providing data in a physiologic setting more closely mimicking the typically active state of children. The test represents a fusion of the fields of two-dimensional echocardiography and cardiovascular stress testing and can be used to assess myocardial perfusion in patients with suspected coronary artery pathology or to evaluate cardiac gradients or functional reserve in patients with noncoronary artery pathology. Testing should be performed with a trained sonographer and attending physician and in collaboration with adult cardiology colleagues. Stress can be administered to the patient through either exercise or pharmacologic agents. Echocardiography is used to assess regional wall motion abnormalities when evaluating myocardial perfusion or gradients and/or function when assessing the patient without coronary artery issues. Conditions with potential coronary artery pathology for which stress echocardiography is appropriate include Kawasaki disease, transplant graft vasculopathy, arterial switch operation for transposition of the great arteries, anomalous coronary artery origins or courses, pulmonary atresia with intact ventricular septum, hyperlipidemia, insulin-dependent diabetes mellitus, and supravalvar aortic stenosis. Stress echocardiography can also be helpful in determining the behavior during activity of gradients in conditions such as hypertrophic cardiomyopathy or aortic and pulmonic stenosis, of cardiac pressures in pulmonary hypertension and of ventricular function in conditions such as dilated cardiomyopathy or mitral and aortic regurgitation.
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PMID:Pediatric stress echocardiography. 1197 81

Diastolic heart failure is defined clinically when signs and symptoms of heart failure are present in the presence of preserved left ventricular systolic function (ejection fraction >45%). The incidence and prevalence of primary diastolic heart failure increases with age and it may be as high as 50% in the elderly. Age, female gender, hypertension, coronary artery disease, diabetes, and increased body mass index are risk factors for diastolic heart failure. Hemodynamic consequences such as increased pulmonary venous pressure, post-capillary pulmonary hypertension, and secondary right heart failure as well as decreased cardiac output are similar to those of systolic left ventricular failure, although the nature of primary left ventricular dysfunction is different. Diagnosis of primary diastolic heart failure depends on the presence of preserved left ventricular ejection fraction. Assessment of diastolic dysfunction is preferable but not mandatory. It is to be noted that increased levels of B-type natriuretic peptide does not distinguish between diastolic and systolic heart failure. Echocardiographic studies are recommended to exclude hypertrophic cardiomyopathy, infiltrative heart disease, primary valvular heart disease, and constrictive pericarditis. Myocardial stress imaging is frequently required to exclude ischemic heart disease. The prognosis of diastolic heart failure is variable; it is related to age, severity of heart failure, and associated comorbid diseases such as coronary artery disease. The prognosis of severe diastolic heart failure is similar to that of systolic heart failure. However, cautious use of diuretics and/or nitrates may cause hypotension and low output state. Heart rate control is essential to improving ventricular filling. Pharmacologic agents such as angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers are used in selected patients to decrease left ventricular hypertrophy. To decrease myocardial fibrosis, aldosterone antagonists have a potential therapeutic role. However, prospective controlled studies will be required to establish their efficacy in primary diastolic heart failure.
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PMID:Primary diastolic heart failure. 1198 32

Atrial fibrillation (AF) is a common clinical problem, particularly in the elderly, and in patients with organic heart disease. A small percentage of patients, have a potentially reversible cause. Atrial fibrillation is in most patients (approximately 70%) associated with chronic organic heart disease including valvular heart disease, coronary artery disease, hypertension, particularly if left ventricular hypertrophy is present, hypertrophic cardiomyopathy, dilated cardiomyopathy and congenital heart disease and most commonly in adults, atrial septal defect. As in many chronic conditions, determining whether AF is the result or is unrelated to the underlying heart disease, remains unclear. The list of possible etiologies also include cardiac amyloidosis, hemochromatosis and endomyocardial fibrosis. Other heart diseases, such as mitral valve prolapse (with or without mitral regurgitation), calcification of the mitral annulus, atrial myxoma, pheochomocytoma and idiopathic dilated right atrium, present a higher incidence of AF. The relationship between these findings and the arrhythmia are still unclear. Atrial fibrillation may occur in the absence of detectable organic heart disease, the so-called "lone AF", in about 30% of cases. The term "lone AF" or "idiopathic AF" implies the absence of any detectable etiology including hyperthyroidism, chronic obstructive lung disease, overt sinus node dysfunction, and overt or concealed preexcitation (Wolf-Parkinson-White syndrome), only to mention a few of other rare causes of AF. In every instance of recently discovered AF, thyrotoxicosis should be ruled out. The autonomous nervous system may contribute to the occurrence of AF in some patients. Atrial fibrillation occurs commonly in patients with valvular heart disease, particularly when it involves the mitral valve. The occurrence of AF is unrelated to the severity of mitral stenosis but is more common in patients with enlarged left atrium and congestive heart failure. In patients with coronary artery disease, Af occurs predominantly in older patients, males and patients with left ventricular dysfunction. Important predictive factors of AF include hypertension, left ventricular hypertrophy and diabetes. However, the relation between AF and hypertension remains unclear. The risk of the development of AF, in an individual patient, is often difficult to assess but increasing age, presence of valvular heart disease and congestive heart failure, increase the risk of AF.
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PMID:Atrial fibrillation, the arrhythmia of the elderly, causes and associated conditions. 1210 96

In the United States alone 300,000-400,000 people die of sudden cardiac death every year. Much of this mortality is assumed to be caused by ventricular tachyarrhythmias. Prolonged QTc reflect cardiac repolarization prolongation and/or increased repolarization inhomogenity known to be associated with increased risk of arrhythmias. The paper gives a review of the possibilities to assess the risk of ventricular arrhythmia and/or cardiac death from QTc. Prolonged QTc may hold independent prognostic importance for mortality in common diseases as ischemic heart disease and diabetes mellitus where as the prognostic importance in heart failure and arterial hypertension is more uncertain. In more rare diseases as the inborn long QT syndrome the QT interval gives not only important hint to the diagnosis but the magnitude also provides information on prognosis. QTc has probably no independent prognostic importance in hypertrophic cardiomyopathy or in the arrhythmogenic right ventricular disease. The degree of QTc prolonging during treatment with QTc prolonging drugs is prognostic for the risk of ventricular arrhythmia in form of torsade de pointes and QTc prolonging drugs should probably not be prescribed for patients with a QTc greater than 460 ms and withdrawn if QTc exceeds 500 ms during treatment. Data from the DIAMOND study suggest that QTc can be used to point out those heart failure patients who will benefit from antiarrhythmic therapy.
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PMID:QTc interval in the assessment of cardiac risk. 1211 54

Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.
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PMID:Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. 1236 29


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