Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skeletal muscle insulin resistance is considered to be the primary defect involved in type 2 diabetes mellitus (T2DM). Despite transcriptome studies in limited T2DM human subjects suggesting an association of T2DM with impaired oxidative phosphorylation in muscle, its molecular pathogenesis remains largely unknown. To identify dysregulated genes and gene networks that are associated with T2DM in human skeletal muscle, we examined expression patterns of 56,318 transcribed genes on 92 T2DM cases and 184 gender-, age- and race-matched non-diabetic controls from the Genotype-Tissue Expression (GTEx) database. RNA-Sequencing data suggest that diabetic skeletal muscle is characterized by decreased expression of genes that are related to insulin resistance (IRS2, MTOR, SLC2A4, and PPARA), carbohydrate, energy, and amino acid metabolism pathways (NDUFS1, NDUFA10, NDUFB4, NDUFB5, NDUFA5, NDUFB10, SDHB, SDHC, ATP5H, ATP5A, and ATP5J). Up-regulated genes in T2DM are mainly enriched in apoptosis pathways (TP53, GADD45A, TNFRSF10B, TP53AIP1, and PMAIP1), and notably include immune-related pathways suggestive of a response to various infectious diseases (C2, CFB, C4A, C4B, C1S, C1R, C3, HLA-DRA, HLA-DMA, HLA-DOA, and HLA-DPB1). These results confirm the essential regulation of impaired insulin signaling and oxidative phosphorylation in the muscle of T2DM patients, and provide novel molecular insights into the pathophysiological mechanisms of T2DM.
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PMID:Transcriptional profiles of type 2 diabetes in human skeletal muscle reveal insulin resistance, metabolic defects, apoptosis, and molecular signatures of immune activation in response to infections. 2784 19

This study evaluated whether metformin might reduce esophageal cancer risk. Patients with type 2 diabetes mellitus diagnosed during 1999-2005 were recruited from the reimbursement database of Taiwan's National Health Insurance. Those newly treated with metformin (n = 288013, "ever users of metformin") or other antidiabetic drugs (n = 16216, "never users of metformin") were followed until December 31, 2011. Sensitivity analyses were conducted in a matched-pair sample of 16216 never users and 16216 ever users. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. The risk associated with infection of Helicobacter pylori, Epstein-Barr virus, hepatitis B virus and hepatitis C virus was also evaluated. Results showed that the incidence of esophageal cancer in ever and never users was 25.03 and 50.87 per 100,000 person-years, respectively. The overall hazard ratio (95% confidence intervals) of 0.487 (0.347-0.684) suggested a significantly lower risk among metformin users. Hazard ratios comparing the first (< 21.47 months), second (21.47-46.00 months) and third (> 46.00 months) tertile of cumulative duration of metformin use to never users was 1.184 (0.834-1.680), 0.403 (0.276-0.588) and 0.113 (0.071-0.179), respectively. Infection of Helicobacter pylori (but not the other viral infections) significantly increased the risk, which could be ameliorated by metformin. Analyses in the matched sample consistently supported a protective role of metformin. In conclusion, metformin reduces esophageal cancer risk when the cumulative duration is more than approximately 2 years.
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PMID:Metformin and esophageal cancer risk in Taiwanese patients with type 2 diabetes mellitus. 2786 Nov 46

The incidence of both type 1 (T1D) and type 2 diabetes (T2D) is drastically increasing, and it is predicted that the global prevalence of diabetes will reach almost 600 million cases by 2035. Even though the pathogenesis of both types of diabetes is distinct, the immune system is actively involved in both forms of the disease. Genetic and environmental factors determine the risk to develop T1D. On the other hand, sedentary life style, surplus of food intake and other lifestyle changes contribute to the increase of T2D incidence. Improved sanitation with high-quality medical treatment is such an environmental factor that has led to a continuous reduction of infectious diseases including helminth infections over the past decades. Recently, a growing body of evidence has implicated a negative association between helminth infections and diabetes in humans as well as animal models. In this review, we discuss studies that have provided evidence for the beneficial impact of helminth infections on T1D and T2D. Possible mechanisms are presented by which helminths prevent T1D onset by mitigating pancreatic inflammation and confer protection against T2D by improving insulin sensitivity, alleviating inflammation, augmenting browning of adipose tissue and improving lipid metabolism and insulin signalling.
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PMID:Immunomodulation by helminths: Similar impact on type 1 and type 2 diabetes? 2786

Healthy lifestyles are integral in preventing and treating common cardiovascular and metabolic diseases. The aim of this study was to observe smoking habits, alcohol intake, physical activity and body mass index over a 10-year period in a population-based cohort, particularly focusing on participants with hypertension and type 2 diabetes mellitus. Included were 4155 participants from the first (2001-2003) and second (2010-2011) follow-ups of the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA). Information was collected via health questionnaire; height and weight were measured. In a healthy lifestyle score one point was attributed per criterion; non-smoking, low risk alcohol consumption, BMI<25kg/m2, and regular physical activity. Overall in 2010-2011, 16.4% were smokers, 7.7% had at risk alcohol consumption, 25.5% were physically inactive and 57.8% were overweight or obese. Both those with hypertension and diabetes had lower mean healthy lifestyle scores than those without disease. Women with incident hypertension from 2001 to 2011 had lower odds of improving their healthy lifestyle score during this time period compared to those without this disease. In contrast, women with incident diabetes had higher odds of lifestyle score improvement. In men, neither hypertension nor diabetes was associated with change in lifestyle score. Our findings suggest that, irrespective of disease status, preventative attention is needed, particularly in regards to physical activity and bodyweight. These needs could be met by population-based interventions, a necessary and suitable option in both preventing and treating the non-communicable disease epidemic which currently faces countries worldwide.
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PMID:Hypertension, diabetes and lifestyle in the long-term - Results from a Swiss population-based cohort. 2801 Nov 35

Lactic acidosis is the most severe adverse effect associated with metformin therapy of type 2 diabetes mellitus. The risk increases in patients with impaired renal function, most commonly due to diabetic nephropathy, and may be augmented when concurrent medication with a negative impact on renal function is used. The authors present a series of three patients who were admitted to a department of infectious diseases for acute gastroenteritis and within a few hours developed shock syndrome caused by severe lactic acidosis due to accumulation of metformin.
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PMID:[Lactic acidosis due to metformin accumulation complicating acute gastroenteritis]. 2814 28

Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important.
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PMID:Can LDL cholesterol be too low? Possible risks of extremely low levels. 2829 77

Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database. RNA-Sequencing data indicates that diabetic skin is characterized by increased expression of genes that are related to immune responses (CCL20, CXCL9, CXCL10, CXCL11, CXCL13, and CCL18), JAK/STAT signaling pathway (JAK3, STAT1, and STAT2), tumor necrosis factor superfamily (TNFSF10 and TNFSF15), and infectious disease pathways (OAS1, OAS2, OAS3, and IFIH1). Genes in cell adhesion molecules pathway (NCAM1 and L1CAM) and collagen family (PCOLCE2 and COL9A3) are downregulated, suggesting structural changes in the skin of T2DM. For the first time, to the best of our knowledge, this pioneer analytic study reports comprehensive unbiased gene expression changes and dysregulated pathways in the non-diseased skin of T2DM patients. This comprehensive understanding derived from whole-genome expression profiles could advance our knowledge in determining molecular targets for the prevention and treatment of T2DM-associated skin disorders.
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PMID:Whole-genome expression analyses of type 2 diabetes in human skin reveal altered immune function and burden of infection. 2842 44

Vitamin D deficiency is a serious public health problem worldwide that affects not only skeletal health, but also a wide range of acute and chronic diseases. However, there is still skepticism because of the lack of randomized, controlled trials to support association studies on the benefits of vitamin D for non-skeletal health. This review was based on articles published during the 1980-2015 obtained from the Cochrane Central Register of controlled trials, MEDLINE and PubMed, and focuses on recent challenges with regard to the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D levels from dietary sources, supplements, and sun exposure. The effect of vitamin D on epigenetic fetal programming and regulation of genes that may potentially explain why vitamin D could have such lifelong comprehensive health benefits is reviewed. Optimization of vitamin D levels in children and adults around the world has potential benefits to improve skeletal health and to reduce the risk of chronic diseases, including some types of cancer, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, and severe cardiovascular disorders such as atherothrombosis, neurocognitive disorders, and mortality.
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PMID:Dysfunctional immunometabolic effects of vitamin D deficiency, increased cardiometabolic risk. Potential epidemiological alert in America? 2844 Jul 55

Genome-wide scans for positive selection have become important for genomic medicine, and many studies aim to find genomic regions affected by positive selection that are associated with risk allele variations among populations. Most such studies are designed to detect recent positive selection. However, we hypothesize that ancient positive selection is also important for adaptation to pathogens, and has affected current immune-mediated common diseases. Based on this hypothesis, we developed a novel linkage disequilibrium-based pipeline, which aims to detect regions associated with ancient positive selection across populations from single nucleotide polymorphism (SNP) data. By applying this pipeline to the genotypes in the International HapMap project database, we show that genes in the detected regions are enriched in pathways related to the immune system and infectious diseases. The detected regions also contain SNPs reported to be associated with cancers and metabolic diseases, obesity-related traits, type 2 diabetes, and allergic sensitization. These SNPs were further mapped to biological pathways to determine the associations between phenotypes and molecular functions. Assessments of candidate regions to identify functions associated with variations in incidence rates of these diseases are needed in the future.
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PMID:Revealing phenotype-associated functional differences by genome-wide scan of ancient haplotype blocks. 2844 22

Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders. This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.
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PMID:The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. 2851 65


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