Abstract
BackgroundGenetic polymorphisms in the PPARD and NOS1AP is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This study was designed to investigate a potential association of PPARD rs2016520 (T/C) and NOS1AP rs12742393 (A/C) polymorphisms with efficacy of nateglinide in newly diagnosed Chinese patients with type 2 diabetes mellitus (T2DM).MethodsSixty patients with newly diagnosed T2DM were enrolled to identify PPARD rs2016520 and NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay (PCR–RFLP). All subjects were treated with nateglinide (360 mg/day) for 8 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 8 weeks of nateglinide treatment.ResultsAfter nateglinide treatment for 8 consecutive weeks, patients with at least one C allele of PPARD rs2016520 showed a smaller decrease in post plasma glucose (PPG), homeostasis model assessment for beta cell function (HOMA-B) than those with the TT genotype did (P < 0.05). In patients with the AA genotype of NOS1AP rs12742393, the drug showed better efficacy with respect to levels of fasting plasma glucose (FPG), fasting serum insulin (FINS), HOMA-B and homeostasis model assessment for insulin resistance (HOMA-IR) than in patients with the AC + CC genotype (P < 0.05). NOS1AP rs12742393 genotype distribution and allele frequency were associated with responsiveness of nateglinide treatment (P < 0.05).ConclusionsThe PPARD rs2016520 and NOS1AP rs12742393 polymorphisms were associated with nateglinide monotherapy efficacy in Chinese patients with newly diagnosed T2DM.Trial registrationChinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.
Highlights
Nateglinide is an important non-sulfonylurea oral hypoglycemic agent that promotes insulin secretion from pancreatic islet beta cells by inhibiting ATP-sensitive K + channels and activating C a2+ channels [1, 2]
Clinical efficacy evaluation of nateglinide To evaluate the effects of PPARD and NOS1AP variations on the efficacy of nateglinide, 60 newly diagnosed type 2 diabetes mellitus (T2DM) patients with various PPARD rs2016520 (C/T) and NOS1AP rs12742393 (A/C) genotypes but with the same SLCO1B1 T521C and CYP2C9*1 genotype were enrolled
Nateglinide significantly decreased the levels of fasting plasma glucose (FPG), post plasma glucose (PPG), hemoglobin A1c (HbA1c), TG, and Total cholesterol (TC), and increased the levels of fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for beta cell function (HOMA-B) and high-density lipoprotein-cholesterol (HDL-C) levels in patients with T2DM after 8 weeks of nateglinide treatment (Table 1)
Summary
Nateglinide is an important non-sulfonylurea oral hypoglycemic agent that promotes insulin secretion from pancreatic islet beta cells by inhibiting ATP-sensitive K + channels and activating C a2+ channels [1, 2]. Considerable interindividual differences in the therapeutic efficacy of nateglinide have been reported in patients with T2DM [1, 2]. The interindividual differences may be attributed to genetic polymorphism of CYP2C9 and SLCO1B1, but not the CYP3A4 polymorphisms [3] This could not elucidate all the causes of various nateglinide responses [4, 5]. Genetic polymorphisms in the PPARD and NOS1AP is associated with type 2 diabetes mellitus (T2DM); there is no evidence about its impact on the therapeutic efficacy of nateglinide. This study was designed to investigate a potential association of PPARD rs2016520 (T/C) and NOS1AP rs12742393 (A/C) polymorphisms with efficacy of nateglinide in newly diagnosed Chinese patients with type 2 diabetes mellitus (T2DM)
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