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- Kufe, Nyuyki Clement, et al.
(författare)
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Protocol for systematic review and meta-analysis of sex hormones and diabetes risk in ageing men and women of African ancestry
- 2019
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:1
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Forskningsöversikt (refereegranskat)abstract
- Aim: To present the protocol of a systematic review and meta-analysis of the available evidence examining the association between sex hormones and type 2 diabetes risk in ageing men and women of African descent.Methods: We shall conduct a comprehensive search of published studies that examined the association between sex hormones and type 2 diabetes risk in men and women aged ≥40 years from 01/01/1980 to 31/03/2018 with no language restriction. Databases to be searched include: PubMed, Scopus, Cochrane Library, Cumulative Index to Nursing and Allied Health, ISI Web of Science, Clinical Trial registries, Google Scholar and institutional websites such as the WHO, American Diabetes Association, International Diabetes Federation, World Diabetes Foundation, European Association for the Study of Diabetes, African Journal Online and ProQuest databases. This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Independent screening for eligible studies using defined criteria and data extraction, will be completed in duplicate. Discrepancies will be resolved by consensus or consultation with a third researcher. Risk of bias of included studies will be assessed by the appropriate Cochrane risk of bias tool. The overall association estimates will be pooled using appropriate meta-analytic techniques. Heterogeneity will be assessed using Cochrane Q statistic and the inconsistency index (I2). The random effects model will be used to calculate a pooled estimate.Ethics and dissemination: No ethics clearance is required as no primary data will be collected. The systematic review and meta-analysis are part of a PhD project at WITS University (Johannesburg, South Africa) and results will be presented at conferences and published in a peer-review journal. The results will guide future population specific interventions.
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| 2. |
- Stomby, Andreas, et al.
(författare)
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Tissue-specific dysregulation of cortisol regeneration by 11 beta HSD1 in obesity : has it promised too much?
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:6, s. 1100-1110
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Forskningsöversikt (refereegranskat)abstract
- Cushing's syndrome, caused by increased production of cortisol, leads to metabolic dysfunction including visceral adiposity, hypertension, hyperlipidaemia and type 2 diabetes. The similarities with the metabolic syndrome are striking and major efforts have been made to find obesity-associated changes in the regulation of glucocorticoid action and synthesis, both at a systemic level and tissue level. Obesity is associated with tissue-specific alterations in glucocorticoid metabolism, with increased activity of the glucocorticoid-regenerating enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) in subcutaneous adipose tissue and decreased conversion of cortisone to cortisol, interpreted as decreased 11 beta HSD1 activity, in the liver. In addition, genetic manipulation of 11 beta HSD1 activity in rodents can either induce (by overexpression of Hsd11b1, the gene encoding 11 beta HSD1) or prevent (by knocking out Hsd11b1) obesity and metabolic dysfunction. Taken together with earlier evidence that non-selective inhibitors of 11 beta HSD1 enhance insulin sensitivity, these results led to the hypothesis that inhibition of 11 beta HSD1 might be a promising target for treatment of the metabolic syndrome. Several selective 11 beta HSD1 inhibitors have now been developed and shown to improve metabolic dysfunction in patients with type 2 diabetes, but the small magnitude of the glucose-lowering effect has precluded their further commercial development. This review focuses on the role of 11 beta HSD1 as a tissue-specific regulator of cortisol exposure in obesity and type 2 diabetes in humans. We consider the potential of inhibition of 11 beta HSD1 as a therapeutic strategy that might address multiple complications in patients with type 2 diabetes, and provide our thoughts on future directions in this field.
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