Abstract:
PURPOSE OF REVIEW:Soon after the first genome-wide association study (GWAS) for type 2 diabetes (T2D) was published, it was hypothesized that rare and low-frequency variants might explain a substantial proportion of disease risk. Rare coding variants in particular were emphasized given their large expected role in disease. This review summarizes the extent to which recent T2D genetic studies provide evidence for or against this hypothesis. RECENT FINDINGS:Following a comprehensive study of T2D genetic architecture using three sequencing and genotyping technologies, four even larger studies have provided a yet higher resolution view of the role of rare and low-frequency coding variation in T2D susceptibility. Empirical evidence strongly suggests that common regulatory variants are the dominant contributor to T2D heritability. However, rare coding variants may nonetheless be pervasive across T2D-relevant genes. A strategy using common variants to map disease genes, and rare coding variants to link molecular gene perturbations to cellular and phenotypic effects, may be an effective means to investigate T2D pathogenesis and potential new therapies.
journal_name
Curr Diab Repjournal_title
Current diabetes reportsauthors
Flannick Jdoi
10.1007/s11892-019-1142-5subject
Has Abstractpub_date
2019-04-08 00:00:00pages
25issue
5eissn
1534-4827issn
1539-0829pii
10.1007/s11892-019-1142-5journal_volume
19pub_type
杂志文章,评审abstract:PURPOSE OF REVIEW:A growing body of epidemiological and experimental data indicate that nutritional or environmental stressors during early development can induce long-term adaptations that increase risk of obesity, diabetes, cardiovascular disease, and other chronic conditions-a phenomenon termed "developmental progra...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-019-1170-1
更新日期:2019-07-20 00:00:00
abstract::Only 21 % of adolescents with type 1 diabetes (T1D) meet glycemic goals set forth by the American Diabetes Association. Adherence to therapy is a particular concern in this population, and the association between poor adherence and worsening glycemic control indicates that there is a critical need to improve adherence...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-015-0621-6
更新日期:2015-08-01 00:00:00
abstract::Cardiovascular disease is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). DM is now recognized as a risk equivalent for coronary heart disease. The lipid profile in patients with type 2 DM is characterized by elevated triglycerides, low levels of high-density lipoprotein cholest...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-007-0036-0
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-014-0555-4
更新日期:2014-12-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-005-0057-5
更新日期:2005-12-01 00:00:00
abstract:PURPOSE OF REVIEW:Gestational diabetes (GDM) is associated with adverse pregnancy and neonatal outcomes and increased maternal risk for subsequent type 2 diabetes. The best diagnostic strategy for GDM is debated and the role of oral antidiabetic medications (OAD) for treatment is unclear. In this paper, we review metho...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-019-1147-0
更新日期:2019-05-09 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-020-01327-7
更新日期:2020-07-30 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-018-0995-3
更新日期:2018-03-21 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-012-0287-2
更新日期:2012-08-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
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更新日期:2014-04-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
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更新日期:2019-12-06 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-017-0878-z
更新日期:2017-07-01 00:00:00
abstract::The Fat mass and obesity associated (FTO) gene is a newly identified genetic factor for obesity. However, the exact molecular mechanisms responsible for the effect of FTO on obesity remain largely unknown. Recent studies from genome-wide associated studies reveal that genetic variants in the FTO gene are associated no...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-014-0486-0
更新日期:2014-01-01 00:00:00
abstract:PURPOSE OF REVIEW:Appetitive behaviors are mediated through homeostatic and reward signaling of brain circuits. There has been increasing interest in the use of neuromodulation techniques aimed at targeting brain regions such as the lateral prefrontal and subcortical regions associated with dysregulation of eating beha...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-019-1250-2
更新日期:2019-12-02 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-013-0398-4
更新日期:2013-10-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-013-0471-z
更新日期:2014-03-01 00:00:00
abstract:PURPOSE OF REVIEW:Evidence-based treatments for prediabetes can prevent and delay the development of type 2 diabetes in adults. In this review, we propose a framework for population-based diabetes prevention that links screening and prevention activities across key stakeholders. We also discuss gaps in current practice...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-018-1090-5
更新日期:2018-09-19 00:00:00
abstract:PURPOSE OF REVIEW:In this brief review, we highlight studies that have contributed to our current understanding of glucose homeostasis by the central nervous system (CNS) leptin-melanocortin system, particularly proopiomelanocortin neurons and melanocortin-4 receptors (MC4R). RECENT FINDINGS:Leptin deficiency is assoc...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-020-01311-1
更新日期:2020-05-26 00:00:00
abstract::Hyperglycemia and dyslipidemia are significant and independent risk factors for the vascular complications in patients with diabetes. They have been suggested to cause cardiovascular pathologic changes in diabetic states through the following molecular mechanisms: formation and accumulation of advanced glycation end p...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-005-0034-z
更新日期:2005-04-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-015-0671-9
更新日期:2015-11-01 00:00:00
abstract::Type 1 diabetes (T1D) is a complex chronic disease that has many facets for successful management. The burden of this management falls largely on the individual and their family members. Self-management has a major influence on T1D health outcomes, and with successful management, children and adolescents with T1D can ...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-014-0544-7
更新日期:2014-01-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-014-0510-4
更新日期:2014-08-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-005-0013-4
更新日期:2005-06-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-004-0055-z
更新日期:2004-12-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章
doi:10.1007/s11892-008-0077-z
更新日期:2008-12-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-007-0060-0
更新日期:2007-10-01 00:00:00
abstract::Cardiovascular disease (CVD) remains the leading cause of death among adults with diabetes, and CVD prevention remains a major challenge. Coronary artery calcium (CAC) score measured by electron beam tomography (EBT) or multi-slice detector computed tomography correlates closely with plaque burden and coronary angiogr...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-013-0379-7
更新日期:2013-06-01 00:00:00
abstract::The common form of hereditary hemochromatosis is an autosomal recessive disorder most prevalent in Caucasians that results in excessive iron storage. The clinical manifestations of hemochromatosis are protean. HFE genotype, which determines the degree of iron overload and duration of disease have profound effects on d...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
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更新日期:2014-01-01 00:00:00
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journal_title:Current diabetes reports
pub_type: 杂志文章,评审
doi:10.1007/s11892-019-1249-8
更新日期:2019-11-04 00:00:00
abstract::The incidence of both type 1 and type 2 diabetes is increasing globally, most likely explained by environmental changes, such as changing exposures to foods, viruses, and toxins, and by increasing obesity. While cardiovascular disease (CVD) mortality has been declining recently, this global epidemic of diabetes threat...
journal_title:Current diabetes reports
pub_type: 杂志文章,评审
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更新日期:2013-06-01 00:00:00