In:
British Journal of Clinical Pharmacology, Wiley, Vol. 74, No. 3 ( 2012-09), p. 501-509
Abstract:
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Repaglinide is an insulin secretagogue agent widely used in the treatment of type 2 diabetes mellitus (T2DM). Obvious interindividual differences in the therapeutic efficacy of and adverse reactions to repaglinide were observed in Chinese T2DM patients. • There are no reports showing the influence of genetic variations of NeuroD1/BETA2 A45T and PAX4 R121W on repaglinide response in Chinese T2DM patients. WHAT THIS STUDY ADDS • This study aimed to investigate the association of genetic polymorphisms of NeuroD1/BETA2 A45T and PAX4 R121W with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients. • The NeuroD1/BETA2 A45T and PAX4 R121W polymorphisms were correlated with repaglinide therapeutic efficacy in Chinese T2DM patients. AIMS We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS Three hundred and sixty‐eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty‐three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day −1 ). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol and high‐density lipoprotein‐cholesterol were determined before and after repaglinide treatment. RESULTS The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P 〈 0.01, odds ratios = 2.342 (1.365, 4.019), P = 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l −1 , P 〈 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l −1 , P 〈 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l −1 , P 〈 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (−2.79 ± 2.14 vs. −0.99 ± 1.80 mmol l −1 , P 〈 0.01) (−3.53, −1.84 vs. −1.99, −0.13) and postprandial plasma glucose (−6.71 ± 5.90 vs. −2.54 ± 3.39 mmol l −1 , P 〈 0.01) (−9.28, −4.62 vs. −4.34, −0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (−6.53 ± 6.52 vs. −2.95 ± 1.17 mmol l −1 , P 〈 0.05) (−8.20, −4.89 vs. −3.92, −1.20). CONCLUSIONS The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
DOI:
10.1111/bcp.2012.74.issue-3
DOI:
10.1111/j.1365-2125.2012.04202.x
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
1498142-7
detail.hit.zdb_id:
188974-6
SSG:
15,3
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