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)

Evidence exists that some clinical, metabolic and genetic risk factors are associated with the development of diabetic retinopathy (DR). The aim of the study was: (1) to define the prevalence of DR in the examined group of 267 patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to identify in cross-sectional analysis, the clinical features associated with DR in the study group; and (3) to search for the association of 4 markers of vitamin D receptor (VDR), a candidate gene for vascular complications in diabetes, with DR. The examined group consisted of 146 female and 121 male T2DM patients (mean age at examination: 61.3+/-9.4 years; age at T2DM diagnosis: 50.0+/-9.2; T2DM duration: 11.3+/-7.8 years; body mass index (BMI): 30.5+/-5.5 kg/m(2); HbA1c: 7.8+/-1.5%). In all patients, the clinical and metabolic profile was determined. Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy after pupillary dilatation. Colour photographic documentation was made. The examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR polymorphisms based on the restriction fragment length polymorphism method. The statistical analysis was performed using univariate and multivariate logistic regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85 (31.8%) patients with T2DM. The multivariate analysis revealed that significant predictors of this complication were: never-smoking status (odds ratio 2.2, 95% confidence interval 1.2-4), urea serum level (1.3, 1.1-1.5), HbA1c level (1.4, 1.1-1.8) and insulin treatment (2.7, 1.4-5.1). Other features such as age of T2DM diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum creatinine level, albumin/creatinine ratio and arterial hypertension were univariate predictors of DR, however they lost significance as independent predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype and haplotype combination of VDR were not associated with the examined complication. However, there was a suggestion of a possible slight association between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that DR in T2DM patients remains a frequent complication in Polish T2DM patients. We were able to confirm the role of some clinical risk factors, surprisingly including not-smoking status, as was previously shown in the UK Prospective Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor for this size of study group.
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PMID:Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients. 1721 61

Type 1 diabetes is considered to be T-helper 1 (Th1) type autoimmune disease. Because the vitamin D receptor is expressed on CD4+T cells and is known to affect cytokine responses, several groups have investigated the association between the vitamin D receptor gene BsmI polymorphism and type 1 diabetes. However, this issue is still controversial; therefore, we examined this gene polymorphism in a large number of type 1 diabetic patients as a multi-center collaborative study in Japan. A total of 1,373 subjects, including 774 cases and 599 control subjects of Japanese origin, were studied. The frequency of carriers of the BB genotype in type 1 diabetic patients was significantly higher than that in controls (p<0.01, odds ratio 3.65). Moreover, IFN-gamma production upon anti-CD3 stimulation in the BB genotype group was significantly higher than that in the Bb and bb genotype groups (p<0.05), suggesting that the polyclonal T cell response in BB genotype patients is Th1 dominant. Based upon these results, we propose that it may be worthwhile to focus on subjects with the BB genotype of this gene polymorphism as having high risk for type 1 diabetes.
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PMID:Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese. 1795 56

Vitamin D has important immuno-modulatory properties and it influences insulin secretion. It acts through a vitamin D receptor (VDR), for which several gene polymorphisms have been described. The Uruguayan population presents several epidemiological characteristics that make it different from that of other counties, including other Latin-American countries. It went through miscegenation processes, with a tri-hybrid European, Amerindian and African origin, with no contribution from isolated Amerindian communities. Such differences have important consequences for the relationship between frequencies of several genes in the general population and their association with the diabetes mellitus. We examined the prevalence of VDR gene polymorphisms in the general population and their relation to type 1 diabetes in a parent-case design. One hundred unrelated individuals from the general population and 45 parent-patient triads with a child affected with type 1 diabetes were genotyped for FokI, BsmI and TaqI VDR gene polymorphisms by RFLP-PCR. We used a transmission disequilibrium test to assess preferential transmission of parents to affected offspring. The prevalence of the three VDR polymorphisms was: allele F = 48%, B = 35%, T = 64%. The f, b, T alleles and heterozygous genotypes were found at a high frequency in this population. Among 36 informative heterozygous parental genotypes, 30 transmitted the F allele (probability of transmission = 83%). The other two polymorphisms did not show significant transmission. We suggest that FokI polymorphism indicates susceptibility to type 1 diabetes mellitus in the Uruguayan population.
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PMID:Prevalence of vitamin D receptor gene polymorphism in a Uruguayan population and its relation to type 1 diabetes mellitus. 1798 6

Vitamin D maintains calcium homeostasis and is required for bone development and maintenance. Recent evidence has indicated an interrelationship between vitamin D and health beyond bone, including effects on cell proliferation and on the immune system. New developments in our lab related to the function and regulation of target proteins have provided novel insights into the mechanisms of vitamin D action. Studies in our lab have shown that the calcium-binding protein, calbindin, which has been reported to be a facilitator of calcium diffusion, also has an important role in protecting against apoptotic cell death in different tissues including protection against cytokine destruction of osteoblastic and pancreatic beta cells. These findings have important implications for the therapeutic intervention of many disorders including diabetes and osteoporosis. Recent studies in our laboratory of intestinal calcium absorption using calbindin-D(9k) null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inducible epithelial calcium channel, TRPV6, provide evidence for the first time of calbindin-D(9k) and TRPV6 independent regulation of active calcium absorption. Besides calbindin, the other major target of 1,25(OH)(2)D(3) in intestine and kidney is 25(OH)D(3) 24 hydroxylase (24(OH)ase), which is involved in the catabolism of 1,25(OH)(2)D(3). In our laboratory we have identified various factors that cooperate with the vitamin D receptor in regulating 24(OH)ase expression including C/EBP beta, SWI/SNF (complexes that remodel chromatin using the energy of ATP hydrolysis) and the methyltransferases, CARM1 and G9a. Evidence is also presented for C/EBP beta as a nuclear coupling factor that coordinates regulation of osteopontin by 1,25(OH)(2)D(3) and PTH. Our findings define novel mechanisms that may be of fundamental importance in understanding how 1,25(OH)(2)D(3) mediates its multiple biological effects.
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PMID:Vitamin D: molecular mechanism of action. 1808 36

We analyzed the genes expressed (transcriptomes) and the proteins translated (pro- teomes) in muscle tissues and activated CD4(+) and CD8(+) T-lymphocytes (T-cells) of five Type 2 diabetes (T2DM) subjects using Affymetrix microarrays and mass spectrometry, and compared them with matched non-diabetic controls. Gene expressions of insulin receptor (INSR), vitamin D receptor, insulin degrading enzyme, Akt, insulin receptor substrate-1 (IRS-1), IRS-2, glucose transporter 4 (GLUT4), and enzymes of the glycolytic pathway were decreased at least 50% in T2DM than in controls. However, there was greater than two-fold gene upregulation of plasma cell glycoprotein-1, tumor necrosis factor alpha (TNFalpha, and gluconeogenic enzymes in T2DM than in controls. The gene silencing for INSR or TNFalpha resulted in the inhibition or stimulation of GLUT4, respectively. Proteome profiles corresponding to molecular weights of the above translated transcriptomes showed different patterns of changes between T2DM and controls. Meanwhile, changes in transcriptomes and proteomes between muscle and activated T-cells of T2DM were comparable. Activated T-cells, analogous to muscle cells, expressed insulin signaling and glucose metabolism genes and gene products. In conclusion, T-cells and muscle in T2DM exhibited differences in expression of certain genes and gene products relative to non-diabetic controls. These alterations in transcriptomes and proteomes in T2DM may be involved in insulin resistance.
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PMID:Transcriptome and proteome expressions involved in insulin resistance in muscle and activated T-lymphocytes of patients with type 2 diabetes. 1826 3

Adynamic bone in patients with chronic kidney disease (CKD) is a clinical concern because of its potential increased risk for fracture and cardiovascular disease (CVD). Prevalence rates for adynamic bone are reportedly increased, although the variance for its prevalence and incidence is large. Differences in its prevalence are largely attributed to classification and population differences, the latter of which constitutes divergent groups of elderly patients having diabetes and other comorbidities that are prone to low bone formation. Most patients have vitamin D deficiency and the active form, 1,25-dihydroxyvitamin D, invariably decreases to very low levels during CKD progression. Fortunately, therapy with vitamin D receptor activators (VDRAs) appears to be useful in preventing bone loss, in part, by its effect to stimulate bone formation and in decreasing CVD morbidity, and should be considered as essential therapy regardless of bone turnover status. Future studies will depend on assessing cardiovascular outcomes to determine whether the risk/reward profile for complications related to VDRA and CKD is tolerable.
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PMID:Adynamic bone in patients with chronic kidney disease. 1833 16

The nontuberculous mycobacteria (NTM) exhibit heterogeneous pathogenicity in humans. Articles on known and potential human factors capable of producing susceptibility to NTM lung disease (NTMLD) were identified by a systematic search of the medical literature, and are reviewed in the present study. Patients with pre-existing structural lung disease are known to be at risk of NTMLD. Other susceptible groups have become recognised since the 1980s, in particular middle-aged nonsmokers without previous lung disease (a group including those with Lady Windermere syndrome) and patients with genetically determined defects of cell-mediated immunity, including abnormalities of the interleukin-12/interferon-gamma axis, certain human leukocyte antigen alleles, cystic fibrosis transmembrane conductance regulator mutations, and polymorphisms of solute carrier 11A1 (or natural resistance-associated macrophage protein 1) and the vitamin D receptor. Information is also accruing about acquired systemic causes of susceptibility to NTMLD, including inhibitory antibodies directed against interferon-gamma, post-menopausal waning of endogenous oestrogen levels, coeliac disease and exposure to use of dietary phyto-oestrogens. It is not known whether immunosuppressive factors, such as oral corticosteroid treatment, chronic renal failure, diabetes mellitus and other known risk factors for pulmonary tuberculosis, are also risk factors for the development of NTMLD. Caution is appropriate in managing such patients.
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PMID:Susceptibility to nontuberculous mycobacterial lung disease. 1851 57

A preponderance of evidence supports a role for vitamin D beyond the classical function in mineral homeostasis. Epidemiologic investigations have revealed a beneficial role of vitamin D in muscle function, cardiovascular health, diabetes, and cancer prevention. More recently, studies have suggested a potential beneficial role of vitamin D in cognitive function. Vitamin D exhibits functional attributes that may prove neuroprotective through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction and detoxification mechanisms. Compelling evidence supports a beneficial role for the active form of vitamin D in the developing brain as well as in adult brain function. The vitamin D receptor and biosynthetic and degradative pathways for the hydroxylation of vitamin D have been found in the rodent brain; more recently these findings have been confirmed in humans. The vitamin D receptor and catalytic enzymes are colocalized in the areas of the brain involved in complex planning, processing, and the formation of new memories. These findings potentially implicate vitamin D in neurocognitive function.
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PMID:Vitamin D and neurocognitive dysfunction: preventing "D"ecline? 1857 97

Endothelial cells detect physical and chemical changes in the blood vessels, and release various factors to counter these changes to maintain homeostasis. Traditional cardiovascular disease risk factors, such as hypertension, dyslipidemia and diabetes, cause endothelial dysfunction characterized by off-balanced vasodilation/vasoconstriction, increased oxidative stress and inflammation, deregulation of thrombosis and fibrinolysis, abnormal smooth muscle cell proliferation, and a deficient repair mechanism. Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular disease and mortality than the general population. Endothelial dysfunction is commonly observed in CKD, likely preceding other cardiovascular complications. Lipid-lowering agents, such as statins, improve endothelial functions and are effective in reducing cardiovascular disease risk in the general population, but have not demonstrated comparable efficacy in the CKD patient population. Similarly, antidiabetic agents, such as thiazolidinediones, that improve endothelial function in the general population are less efficacious than expected in slowing disease progression and reducing cardiovascular disease risk in CKD patients. Interestingly, agents that activate the vitamin D receptor (VDR) for the treatment of hyperparathyroidism secondary to CKD are associated with a survival benefit in CKD patients that is likely mediated through the effects of the VDR on modulating key components involved in endothelial dysfunction. However, a randomized, clinical study is required to confirm the survival benefit of VDR activation therapy for CKD patients. Results from clinical studies suggest that managing hypertension alone may not be adequate in slowing CKD progression and its related cardiovascular complications. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers that target the renin-angiotensin system slow CKD progression, possibly due to their effects on improving endothelial function, independent of controlling blood pressure.
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PMID:Endothelial dysfunction and chronic kidney disease: treatment options. 1872 4

Vitamin D, the sunshine vitamin, is important for childhood bone health. Over the past two decades, it is now recognized that vitamin D not only is important for calcium metabolism and maintenance of bone health throughout life, but also plays an important role in reducing risk of many chronic diseases including type I diabetes, multiple sclerosis, rheumatoid arthritis, deadly cancers, heart disease and infectious diseases. How vitamin D is able to play such an important role in health is based on observation that all tissues and cells in the body have a vitamin D receptor, and, thus, respond to its active form 1,25-dihydroxyvitamin D. However, this did not explain how living at higher latitudes and being at risk of vitamin D deficiency increased risk of these deadly diseases since it was also known that the 1,25-dihydroxyvitamin D levels are normal or even elevated when a person is vitamin D insufficient. Moreover, increased intake of vitamin D or exposure to more sunlight will not induce the kidneys to produce more 1,25-dihydroxyvitamin D. The revelation that the colon, breast, prostate, macrophages and skin among other organs have the enzymatic machinery to produce 1,25-dihydroxyvitamin D provides further insight as to how vitamin D plays such an essential role for overall health and well being. This review will put into perspective many of the new biologic actions of vitamin D and on how 1,25-dihydroxyvitamin D is able to regulate directly or indirectly more than 200 different genes that are responsible for a wide variety of biologic processes.
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PMID:The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. 1880 84


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