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)

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

Primary lipodystrophies represent a heterogeneous group of very rare diseases with a prevalence of less than 1 case for 100.000, inherited or acquired, caracterized by a loss of body fat either generalized or localized (lipoatrophy). In some forms, lipoatrophy is associated with a selective hypertrophy of other fat depots. Clinical signs of insulin resistance are often present: acanthosis nigricans, signs of hyperandrogenism. All lipodystrophies are associated with dysmetabolic alterations with insulin resistance, altered glucose tolerance or diabetes and hypertriglyceridemia leading to a risk of acute pancreatitis. Chronic complications are those resulting from diabetes involving the retina, kidney and nerves, cardiovascular complications and steatotic liver lesions that could result in cirrhosis. Genetic forms of generalized lipodystrophy (or Berardinelli-Seip syndrome) result, in most cases, from recessive mutations in one of two genes: either BSCL2 coding seipin or BSCL1 coding AGPAT2, an acyl-transferase involved in triglyceride synthesis. Acquired generalized lipodystrophy (Lawrence syndrome) is of unknown origin but is sometimes associated with signs of autoimmunity. Partial lipodystrophies can be familial with dominant transmission. Heterozygous mutations have been identified in the LMNA gene encoding nuclear lamin A/C belonging to the nuclear lamina, or in PPARG encoding the adipogenic transcription factor PPARgamma. Some less typical lipodystrophies, associated with signs of premature aging, have been linked to mutations in LMNA or in the ZMPSTE24 gene encoding the protease responsible for the maturation of prelamin A into lamin A. Acquired partial lipodystrophy (Barraquer-Simons syndrome) is characterized by cephalothoracic fat loss. Its aetiology is unknown but mutations in LMNB2, encoding the lamina protein lamin B2, could represent susceptibility factors. Highly active antiretroviral treatments for HIV infection are currently the most frequent cause of acquired secondary lipodystrophic syndromes. The genetic diagnosis is performed in specialized laboratories and, in the most severe forms, antenatal diagnosis could be proposed. Treatment of diabetes, dyslipidemia and complications involves the classical intervention strategies. Insulino-sensitizing drugs are useful. Therapeutic trials with recombinant human leptin in patients with very low leptin levels reported good results with respect to the metabolic and liver alterations. The prognosis is linked to the precocity and severity of the diabetic, cardiovascular and liver complications.
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PMID:[Primary lipodystrophies]. 1732 32

Telomeres serve as a mitotic clock and biological marker of senescence. Diabetes mellitus (DM) is associated with damage to target organs and premature aging. We assessed the effect of glycemic control on telomere dynamics in arterial cells of 58 patients undergoing coronary artery bypass and in mononuclear blood cells of other diabetic (32 type I and 47 type II) patients comparing well controlled to uncontrolled patients. All were compared to age-dependent curve of healthy controls. Telomeres were significantly shorter in the arteries of diabetic versus non-diabetic patients (p=0.049) and in mononuclear cells of both type I and type II diabetes. In all study groups good glycemic control attenuated shortening of the telomeres. In arterial cells good glycemic control attenuated, but not abolished, the telomere shortening. In type II DM the mononuclear telomere attrition was completely prevented by adequate glycemic control. Telomere shortening in mononuclear cells of type I diabetic patients was attenuated but not prevented by good glycemic control. Results of this study suggest that diabetes is associated with premature cellular senescence which can be prevented by good glycemic control in type II DM and reduced in type I DM.
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PMID:Telomere dynamics in arteries and mononuclear cells of diabetic patients: effect of diabetes and of glycemic control. 1770 20

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in Japan and other Westernized countries. Over 50% of the ESRD patients die from cardiovascular events. Cardiovascular disease (CVD) in ESRD patients with diabetes mellitus (DM) are implicated in the endothelial dysfunction caused by hyperglycemia, hyperlipidemia, and hypertension, and in the vascular calcification of intimal and medial arterial blood vessels caused by hyperphosphatemia. Therefore, dietary control of hyperglycemia and hyperphosphatemia should play an important role in the management of ESRD patients with DM. Furthermore, recent findings suggest that high concentrations of serum phosphate, even if within the normal range, may be a risk factor for CVD and mortality. An in vivo study using klotho knockout mice and fibroblast growth factor 23 (FGF-23) knockout mice has revealed that correction of hyperphosphatemia and hypervitaminosis D could ameliorate the premature aging-like phenotype. A low glycemic index and low phosphate diet may provide an advantage in the prevention of aging-related diseases in healthy individuals as well as in those with chronic kidney disease.
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PMID:Advantage of a low glycemic index and low phosphate diet on diabetic nephropathy and aging-related diseases. 1787 88

Werner syndrome (WS) is a rare autosomal recessive genetic instability/cancer predisposition disorder that displays many symptoms of premature aging. The mimicry of agerelated phenotypes in WS, as well as its dependence on a single defective gene product, has provided the impetus for studying this fascinating disease as a model system for normative aging and its related pathologies such as atherosclerosis, neoplasia, diabetes mellitus, and osteoporosis. The gene product defective in WS, WRN, is a member of the RecQ DNA helicase family that is widely distributed in all kingdoms of life, and is believed to play a central role in genomic stability by preferentially operating on non-canonical DNA structures. Although there have been considerable advances in our understanding of the biochemistry of WRN and its interacting protein partners, the in vivo molecular function(s) of WRN remain(s) elusive. In addition to summarizing the features and clinical progression of WS, the following chapter details our current understanding of the WRN protein with respect to its biochemistry and its interacting protein partners, and considers its putative in vivo roles in various DNA transactions.
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PMID:Werner Syndrome, aging and cancer. 1872 62

Recent studies using genetically modified mice, such as FGF23-/- and Klotho-/- mice that exhibit altered mineral homeostasis due to a high vitamin D activity showed features of premature aging that include retarded growth, osteoporosis, atherosclerosis, ectopic calcification, immunological deficiency, skin and general organ atrophy, hypogonadism and short lifespan. The phenotype reversed by normalizing vitamin D and/or mineral homeostasis. Thus, hypervitaminosis D due to an increased 1alpha-hydroxylase activity seems to be a cause of the premature aging. In several studies, we have described that a complete or partial lack of vitamin D action (VDR-/- mice and CYP27B1-/-) show almost similar phenotype as FGF23-/- or Klotho-/- mice. VDR mutant mice have growth retardation, osteoporosis, kyphosis, skin thickening and wrinkling, alopecia, ectopic calcification, progressive loss of hearing and balance as well as short lifespan. CYP27B1-/- mice do not show alopecia nor balance deficit, which might be apoVDR-dependent or calcidiol-dependent. The features are typical to premature aging. The phenotype is resistant to a normalization of the mineral homeostasis by a rescue diet containing high calcium and phosphate. Taken together, aging shows a U-shaped dependency on hormonal forms of vitamin D suggesting that there is an optimal concentration of vitamin D in delaying aging phenomena. Our recent study shows that calcidiol is an active hormone. Since serum calcidiol but not calcitriol is fluctuating in physiological situations, calcidiol might determine the biological output of vitamin D action. Due to its high serum concentration and better uptake of calcidiol-DBP by the target cells through the cubilin-megalin system, calcidiol seems to be an important circulating hormone. Therefore, serum calcidiol might be associated with an increased risk of aging-related chronic diseases more directly than calcitriol. Aging and cancer seem to be tightly associated phenomena. Accumulation of damage on DNA and telomeres cause both aging and cancer, moreover the signalling pathways seem to converge on tumour suppressor protein, p53, which seems to be regulated by vitamin D. Also, the insulin-like growth factor signalling pathway (IGF-1, IGFBPs, IGFR) and fibroblast growth factor-23 (FGF-23) regulate growth, aging and cancer. Vitamin D can regulate these signalling pathways, too. Also NF-kappaB and telomerase reverse transcriptase (TERT) might be molecular mechanisms mediating vitamin D action in aging and cancer. Calcidiol serum concentrations show a U-shaped risk of prostate cancer suggesting an optimal serum concentration of 40-60 nmol/L for the lowest cancer risk. Therefore, it is necessary to study several common aging-associated diseases such as osteoporosis, hypertension and diabetes known to be vitamin D-dependent before any recommendations of an optimal serum concentration of calcidiol are given.
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PMID:Vitamin D and aging. 1944 37

Werner's syndrome (WS) is an autosomal recessive disorder characterized by premature aging. The main features of the disease are scleroderma-like skin appearance, premature atherosclerosis, short stature, diabetes mellitus, early osteoporosis and early aging. Herein, we describe a patient with WS, who has scleroderma-like skin changes and discuss the literature about WS as a disease in the differential diagnosis of systemic sclerosis.
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PMID:Werner's syndrome: a quite rare disease for differential diagnosis of scleroderma. 1949 68

This is a mini-review of vitamin D(3), its active metabolites and their functioning in the central nervous system (CNS), especially in relation to nervous system pathologies and aging. The vitamin D(3) endocrine system consists of 3 active calcipherol hormones: calcidiol (25OHD(3)), 1alpha-calcitriol (1alpha,25(OH)2D(3)) and 24-calcitriol (24,25(OH)2D(3)). The impact of the calcipherol hormone system on aging, health and disease is discussed. Low serum calcidiol concentrations are associated with an increased risk of several chronic diseases including osteoporosis, cancer, diabetes, autoimmune disorders, hypertension, atherosclerosis and muscle weakness all of which can be considered aging-related diseases. The relationship of many of these diseases and aging-related changes in physiology show a U-shaped response curve to serum calcidiol concentrations. Clinical data suggest that vitamin D(3) insufficiency is associated with an increased risk of several CNS diseases, including multiple sclerosis, Alzheimer's and Parkinson's disease, seasonal affective disorder and schizophrenia. In line with this, recent animal and human studies suggest that vitamin D insufficiency is associated with abnormal development and functioning of the CNS. Overall, imbalances in the calcipherol system appear to cause abnormal function, including premature aging, of the CNS.
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PMID:Vitamin D, nervous system and aging. 1966 Aug 71

Mitochondria are major compartments in cells responsible for generating reactive oxygen species, which can cause the development of diabetes, Parkinson's disease and premature aging. Antioxidant systems in mitochondria are important for the prevention of diseases and reduction in the speed of aging. We investigated whether the reactive oxygen species generated in mitochondria induced the expression of metallothionein as an antioxidant. We compared the expression level of metallothionein mRNA in mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx)-overexpressed (PHGPx-ov) cells with that in control cells. These cells were treated with respiratory inhibitors, including rotenone and 2, 4-dinitrophenol; under these conditions, the PHGPx-ov cells were more resistant to cell death than the control cells. In addition, the intracellular reactive oxygen species level that was induced by these inhibitors was lower in PHGPx-ov cells than in control cells. This indicates that PHGPx degrades the membrane phospholipid hydroperoxide that is formed via the reactive oxygen species generated in mitochondria. The enhanced expression of metallothionein-I and metallothionein-II mRNA in rotenone-treated control cells was significantly decreased in rotenone-treated PHGPx-ov cells, suggesting that the hydrogen peroxide that is formed by superoxide anions generated in mitochondria diffuse into the cytosol and induce metallothionein mRNA expression. Conversely, the expression of manganese-superoxide dismutase (Mn-SOD) mRNA, which is localized in mitochondria, was not correlated with the intracellular reactive oxygen species level that was induced by rotenone treatment. These results suggest that metallothionein expression is sensitively and strictly regulated by the oxidative state that is induced by mitochondrial respiration.
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PMID:Enhanced metallothionein gene expression induced by mitochondrial oxidative stress is reduced in phospholipid hydroperoxide glutathione peroxidase-overexpressed cells. 1981 60

Worldwide epidemic scale of Diabetes mellitus (DM) has been underestimated for a long time. Currently every 10 seconds one patient dies of diabetes-related pathologies. Given the high risk and prevalence of secondary complications as well as individual predisposition to target organ injury, DM is one of the best examples for the application of predictive diagnostics aimed at preventive measures and personalized treatment approaches. Generally there are three levels in desirable pre- and Diabetes care: 1st level: prediction of the predisposition early in childhood. 2nd level: prediction of early/premature aging and prestages of Diabetes. 3rd level: prediction of Diabetes-related complications - cardiovascular, neurodegenerative and cancer diseases frequently developed in Diabetics. Predictive diagnosis is considered as the basis for targeted preventive measures and consequent creation of individualized treatment approaches. Communication among the professionals - healthcare providers, policy-makers, educators, etc., obligatory involved in the overall process to improving (pre)Diabetes care is of paramount importance.
Curr Diabetes Rev 2010 Jan
PMID:Advanced Diabetes care: three levels of prediction, prevention & personalized treatment. 2003 68


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