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)

Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and epsilon2/epsilon3/epsilon4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (epsilon2, epsilon3 and epsilon4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of epsilon2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/107 (6.5%); P < 0.05]. Therefore, our results suggest that the epsilon2 allele/APOE might be a risk factor for diabetes in the Brazilian population.
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PMID:Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients. 1686 78

Wolfram syndrome (WFS1, OMIM 222300) is a rare genetic disorder associated with multiple organ abnormalities, most prominently optic nerve atrophy and diabetes. Mutations in the WFS1 gene coding for wolframin have been identified. The pathogenesis for optic nerve atrophy remains elusive. We here tested the hypothesis that wolframin is expressed in glial cells of the optic nerve and in retinal ganglion cells in the cynomolgus monkey. Paraffin sections through the retina and optic nerve were examined with immunohistochemistry using affinity-purified antibodies to wolframin. Retinal ganglion cells and optic nerve glial cells were found to be strongly labeled. Dual dysfunction of wolframin in optic nerve glial cells and retinal ganglion cells may explain the progressive optic nerve atrophy in Wolfram syndrome.
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PMID:Wolfram syndrome 1 (WFS1) protein expression in retinal ganglion cells and optic nerve glia of the cynomolgus monkey. 1692 72

Type 1A diabetes (T1D) is an autoimmune disorder the risk of which is increased by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)]. The genotype associated with the highest risk for T1D is the DR3/4-DQ8 (DQ8 is DQA1*0301, DQB1*0302) heterozygous genotype. We determined HLA-DR and -DQ genotypes at birth and analyzed DR3/4-DQ8 siblings of patients with T1D for identical-by-descent HLA haplotype sharing (the number of haplotypes inherited in common between siblings). The children were clinically followed with prospective measurement of anti-islet autoimmunity and for progression to T1D. Risk for islet autoimmunity dramatically increased in DR3/4-DQ8 siblings who shared both HLA haplotypes with their diabetic proband sibling (63% by age 7, and 85% by age 15) compared with siblings who did not share both HLA haplotypes with their diabetic proband sibling (20% by age 15, P < 0.01). 55% sharing both HLA haplotypes developed diabetes by age 12 versus 5% sharing zero or one haplotype (P = 0.03). Despite sharing both HLA haplotypes with their proband, siblings without the HLA DR3/4-DQ8 genotype had only a 25% risk for T1D by age 12. The risk for T1D in the DR3/4-DQ8 siblings sharing both HLA haplotypes with their proband is remarkable for a complex genetic disorder and provides evidence that T1D is inherited with HLA-DR/DQ alleles and additional MHC-linked genes both determining major risk. A subset of siblings at extremely high risk for T1D can now be identified at birth for trials to prevent islet autoimmunity.
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PMID:Extreme genetic risk for type 1A diabetes. 1696

Most children who are normal weight for height and otherwise healthy have risk factor levels associated with the absence of heart disease (ie, they do not smoke, do not have diabetes, are physically active, have low-density lipoprotein levels < 110 mg/dL, and have blood pressure < 120/80 mm Hg). However, by adolescence, the earliest lesions in the atherosclerotic process, fatty streaks and raised lesions, are present in the coronary arteries and the abdominal aorta. The severity of early atherogenesis is related to the coexistence of the major cardiovascular risk factors. Most commonly, the associated risk disturbances are mild: borderline hypertension, mild dyslipidemia, insulin resistance, overweight, physical inactivity, and initiation of tobacco use. Rarely, more severe risk factors are present: familial hypercholesterolemia (a genetic disorder of lipid metabolism), diabetes mellitus, secondary hypertension of long standing, or risk factors associated with chronic conditions such as end-stage renal disease. Thus, cardiovascular risk management in this age group has two components: primordial prevention (the prevention of the development of cardiovascular risk in the first place) and primary prevention (more aggressive treatment of identified risk factors in high-risk individuals either through behavioral or pharmacologic means). Trials beginning in adolescence of the primary prevention of atherosclerosis-related diseases have not been undertaken; thus, the decision to initiate pharmacologic management in high-risk adolescents requires careful thought.
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PMID:Cardiovascular risk factors in adolescents. 1703 66

The search for genes involved in the pathogenesis of stroke has been highlighted as a field of needs. We followed the concept, that stroke represents a complex genetic disorder, and analyzed the contribution of 106 informative single nucleotide polymorphisms (SNPs) from 63 candidate genes for cardiovascular diseases for the risk of stroke. We conducted two independent case-control studies in two different German regions and recruited a total of 1,901 hospitalized stroke cases and 1,747 regional population controls. The smaller of both studies was used as the replication study. Multiplex PCR in combination with allele-specific hybridization was used for genotype determination. Descriptive statistics, permutations and multivariable logistic regression were used in the analyses. After permutation testing 5 SNPs, located in the nitric oxide synthase 3, the alpha 2 integrin, the interleukin 13, the selectin P and the chemokine receptor 2 genes, had a significant allele difference between cases and controls in the larger study. For one of these SNPs, the glu298asp polymorphism in the nitric oxide synthase 3 gene, an association with ischemic stroke was replicated in the second study and also in a combined analysis of both studies. This association was independent of age, gender, hypertension, diabetes and hypercholesterolemia in both studies. Using large sample sizes and a replication study approach, we found evidence for a role of a polymorphism in the nitric oxide synthase 3 gene in stroke onset.
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PMID:The glu298asp polymorphism in the nitric oxide synthase 3 gene is associated with the risk of ischemic stroke in two large independent case-control studies. 1716 44

Werner's syndrome (WS) is a rare hereditary disorder which is characterized by clinical signs of premature aging. A 31-year-old man presented with a 12-year history of hoarseness. Also noted were diabetes mellitus, cataracts, scleroderma-like skin atrophy, osteoporosis, and hypogonadism. A clinical diagnosis of WS was made. Laryngoscopy revealed bowed vocal folds resulting in a spindle-shaped closure with glottal incompetence during phonation. We used Gortex for medialization of the middle part of vocal fold to correct the glottal gap in this patient. Despite correction of glottal incompetence in patients with WS, quality of voice could not be improved to that of age-matched normal individuals.
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PMID:Werner's syndrome: a rare cause of hoarseness. 1724 70

Endothelial dysfunction, insulin resistance, and elevated levels of circulating proinflammatory markers are among the earliest detectable abnormalities in people at risk for atherosclerosis. Accelerated atherosclerosis is a leading contributor to morbidity and mortality in type 2 diabetes mellitus, a complex genetic disorder. Therefore, we hypothesized that normoglycemic offspring of patients with type 2 diabetes mellitus (NOPD) may have impaired vascular and metabolic function related to an enhanced proinflammatory state. We compared NOPD (n = 51) with matched healthy control subjects without family history of diabetes (n = 35). Flow- and nitroglycerin-mediated brachial artery vasodilation were assessed by ultrasound to evaluate endothelium-dependent and -independent vascular function. Each subject also underwent an oral glucose tolerance test to evaluate metabolic function. Fasting levels of plasma adiponectin and circulating markers of inflammation (high-sensitivity C-reactive protein, CD40 ligand, interleukin 1beta, tumor necrosis factor alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule) were measured. Both NOPD and the control group had fasting glucose and insulin levels well within the reference range. However, results from oral glucose tolerance test and quantitative insulin sensitivity check index revealed that NOPD were insulin resistant with significantly impaired flow- and nitroglycerin-mediated dilation compared with the control group. Adiponectin levels were lower, whereas many circulating markers of inflammation were higher, in NOPD compared with the control group. Normoglycemic offspring of patients with type 2 diabetes mellitus have impaired vascular and metabolic function accompanied by an enhanced proinflammatory state that may contribute to their increased risk of diabetes and its vascular complications.
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PMID:Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus. 1729 32

A novel pigmented dermatosis was observed in four unrelated boys, three of whom had insulin-dependent diabetes. Three patients were the offspring of consanguineous parents. All four boys had pigmented hypertrichotic patches or induration on the upper inner thighs, with variable involvement of the genitalia, trunk, and limbs. Two boys had episcleritis and orbital proptosis with similar facies and musculoskeletal abnormalities including clinodactyly, flat feet, and short stature. One child had paraaortic and inguinal lymphadenopathy and three patients had an enlarged liver and spleen. A large, swollen pancreas was observed on ultrasound imaging in one patient with insulin dependent diabetes who also had echocardiographic evidence of pericardial inflammation. Three boys had elevated laboratory markers of inflammation. Biopsy specimens from the skin and orbit showed a chronic inflammatory cell infiltrate composed of polyclonal lymphocytes, histiocytes, and plasma cells; fibrosis was observed in two patients, one of whom had previously received radiation therapy to the orbit. Two boys responded to treatment with subcutaneous interferon-alpha, combined with a short course of oral prednisone in the child without diabetes. We believe these inflammatory pigmented skin lesions represent a unique dermatosis associated with diabetes mellitus and systemic disease. The pathogenesis is unknown. The presence of consanguinity in three of four families, and similar dysmorphic features in two boys, suggest a genetic disorder, possibly with autosomal recessive inheritance.
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PMID:Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder? 1746 1

Prader-Willi syndrome (PWS) is a rare, multifaceted genetic disorder resulting from the absence of normally active paternally expressed genes from the 15q11-q13 chromosome region. Due to a lack of anthropometric and intellectual data in Taiwan, we attempted these evaluations. Twenty patients (14 males/6 females) aged 7-23 years with molecularly confirmed PWS were enrolled with parental consent. Their mean height standard deviation score (SDS) was -1.26 +/- 1.89 (from -4.3 to +2.16); mean weight SDS was +1.77 +/- 2.00 (from -0.44 to +5.89); mean body mass index SDS was +3.84 +/- 10.54 (from -0.08 to +10.48); and mean body fat tissue SDS was 39.4 +/- 10.54% (14.7-57.8%) by an InBody 3.0 analyzer. All were hypogonadal. Nine of them had once been given growth hormone therapy, and were taller and slimmer than the rest. Their intelligence tests showed full intelligence quotient = 52.0 +/- 7.6; verbal intelligence quotient = 55.9 +/- 8.77; performance intelligence quotient = 53.2 +/- 9.0. Chronic health status revealed that diabetes was prevalent among the older population. Their IQ was in the range of those with moderate retardation.
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PMID:Anthropometric and intellectual evaluation of individuals with Prader-Willi syndrome. 1758 47

Anesthesia for patients with Steinert's syndrome (myotonic dystrophy, MD) is a challenge for the anaesthetist. MD is a multisystemic disease and the neuromuscular symptoms can be associated with sleep apnea, endocrine disorders (diabetes, hypogonadism, hypothyroidism), cardiac, gastroenteric or cognitive disorders (mental deficiency, attention disorders). The diagnosis is facilitated when one or more of these symptoms are associated with the neuromuscular symptoms; however, the latter are not always present at the onset, which makes the diagnosis of MD a difficult and often late one. The choice of drugs and the choice of anesthesia in these patients can be very challenging for many reasons. A myotonic crisis can be triggered by several factors including hypothermia, shivering and mechanical or electrical stimulation. These patients are very sensitive to the usual anesthetics such as hypnotics and paralyzing agents (both depolarizing and nondepolarizing). The following case report describes pathophysiological considerations and a technique for anaesthesia during thoracic surgery that has been able to assure hemodynamic peroperative stability, early extubation and prolonged respiratory autonomy in a patient affected by this genetic disorder.
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PMID:Anesthesia and myotonic dystrophy (Steinert's syndrome). The role of total intravenous anesthesia with propofol, cisatracurium and remifentanyl. Case report. 1766 Jul 41


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