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Joint effects of diabetic-related genomic loci on the therapeutic efficacy of oral anti-diabetic drugs in Chinese type 2 diabetes patients.
- Source :
-
Scientific reports [Sci Rep] 2016 Mar 17; Vol. 6, pp. 23266. Date of Electronic Publication: 2016 Mar 17. - Publication Year :
- 2016
-
Abstract
- Previous pharmacogenomic studies of oral anti-diabetic drugs have primarily focused on the effect of a single site. This study aimed to examine the joint effects of multiple loci on repaglinide or rosiglitazone efficacy in newly diagnosed type 2 diabetes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks. The reductions in fasting glucose (ΔFPG), 2h glucose (Δ2hPG) and glycated hemoglobin (ΔHbA1c) levels were significantly associated with genetic score that was constructed using the sum of the effect alleles both in the repaglinide (P = 0.0011, 0.0002 and 0.0067, respectively) and rosiglitazone cohorts (P = 0.0002, 0.0014 and 0.0164, respectively) after adjusting for age, gender, body mass index and dosage. Survival analyses showed a trend towards a greater attainment rate of target HbA1c level in individuals with a high genetic score in the repaglinide cohort and rosiglitazone cohort (Plog-rank = 0.0815 and 0.0867, respectively) when the attainment of treatment targets were defined as more than 20% decrease of FPG, 2hPG, and HbA1c levels after treatment. In conclusion, we identified the joint effects of several T2DM-related loci on the efficacy of oral anti-diabetic drugs; moreover, we built a model to predict the drug efficacy.
- Subjects :
- Administration, Oral
Adult
Alleles
Blood Glucose analysis
Body Mass Index
Carbamates therapeutic use
China
Diabetes Mellitus, Type 2 genetics
Drug Administration Schedule
Female
Genetic Loci
Genotype
Glucose Tolerance Test
Glycated Hemoglobin analysis
Humans
Linear Models
Male
Middle Aged
Piperidines therapeutic use
Polymorphism, Single Nucleotide
Rosiglitazone
Thiazolidinediones therapeutic use
Asian People genetics
Diabetes Mellitus, Type 2 drug therapy
Hypoglycemic Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26983698
- Full Text :
- https://doi.org/10.1038/srep23266