A Combined Analysis of 48 Type 2 Diabetes Genetic Risk Variants Shows No Discriminative Value to Predict Time to First Prescription of a Glucose Lowering Drug in Danish Patients with Screen Detected Type 2 Diabetes
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Le résumé fourni par la source
OBJECTIVE: To investigate the genetic influence of 48 type 2 diabetes susceptibility variants on disease progression measured as risk of early prescription redemption of glucose lowering drugs in screen-detected patients with type 2 diabetes. METHODS: We studied type 2 diabetes progression in 1,480 patients with screen-detected type 2 diabetes from the ADDITION-Denmark study using information of redeemed prescriptions from the Register of Medicinal Products Statistics from 2001-2009 in Denmark. Patients were cluster randomized by general practitioners, who were randomized to treat type 2 diabetes according to either a conventional or a multifactorial intensive treatment algorithm. We investigated the genetic influence on diabetes progression by constructing a genetic risk score (GRS) of all 48 validated type 2 diabetes susceptibility variants, a GRS of 11 variants linked to β-cell function and a GRS of 3 variants linked to insulin sensitivity and assessed the association between number of risk alleles and time from diagnosis until first redeemed prescription of either any glucose lowering drug or an insulin drug. RESULTS: The GRS linked to insulin sensitivity only nominally increased the risk of an early prescription redemption with an insulin drug by 39% (HR [95% C.I.] = 1.39 [1.09-1.77], p = 0.009] in patients randomized to the intensive treatment group. Furthermore, the strongest univariate predictors of diabetes progression for the intensive treatment group (measured as time to first insulin) were younger age (HR [95% C.I.] = 0.96 [0.93-0.99]), increased BMI (1.05 [1.01-1.09]), increased HbA1c (1.50 [1.36-.66]), increased TG (1.24 [1.11-1.39]) and reduced fasting serum HDL (0.37 [0.17-0.80]) at baseline. Similar results were obtained for the conventional treatment group. CONCLUSION: Higher levels of HbA1c, fasting circulating levels of triglyceride, lower HDL, larger BMI and younger age are significant determinants of early pharmacological intervention in type 2 diabetes. However, known common type 2 diabetes-associated gene variants do not appear to significantly affect disease progression.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A Combined Analysis of 48 Type 2 Diabetes Genetic Risk Variants Shows No Discriminative Value to Predict Time to First Prescription of a Glucose Lowering Drug in Danish Patients with Screen Detected Type 2 Diabetes
- Date Crossref
- 26/08/2014
- Éditeur
- Public Library of Science (PLoS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Copenhagen pays non établi dans la noticeUniversité ou école supérieure
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Novo Nordisk Foundation pays non établi dans la noticeStructure de recherche
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Steno Diabetes Centers pays non établi dans la noticeÉtablissement de santé
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Glostrup Hospital pays non établi dans la noticeÉtablissement de santé
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Capital Region of Denmark pays non établi dans la noticeOrganisme public
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Aarhus University Department of Public Health pays non établi dans la noticeUniversité ou école supérieure
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University of Southern Denmark pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Health and Medical Sciences The Novo Nordisk Foundation Center for Basic Metabolic Research pays non établi dans la noticeUniversité ou école supérieure
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School of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Steno Diabetes Center A/S pays non établi dans la noticeInstitution
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Research Centre for Prevention and Health pays non établi dans la noticeStructure de recherche
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Public Research Centre for Health pays non établi dans la noticeStructure de recherche
University of Copenhagen, Novo Nordisk Foundation et Steno Diabetes Centers, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.