scholarly journals Evaluation of the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating type 2 diabetes among Chinese Han patients

2019 ◽  
Author(s):  
jinfang song ◽  
Mingzhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
Yi-Qing Zhao

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 newly diagnosed T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Result: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). A total of 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a less reduction in fasting plasma glucose (FPG) levels with a less increase in homeostasis model assessment for β cell HOMA-β in the carriers of G allele at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.

2019 ◽  
Author(s):  
Jinfang Song ◽  
Mingzhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
Yi-Qing Zhao

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Results: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a reduction in fasting plasma glucose (FPG) levels with an increase in homeostasis model assessment for β cell HOMA-β in the carriers of genotype CG + GG at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers. Trial registration: This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536).


2021 ◽  
Author(s):  
Jin-Fang Song ◽  
Jie Zhang ◽  
Ming-Zhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
...  

Abstract Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P < 0.05). Post 8-week of treatment, newly diagnosed T2DM patients showed a less reduction in fasting plasma glucose levels and less increase in the carriers of genotype CG + GG at rs10830963 when compared with the CC genotype (P < 0.05). MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers. Trial registration: Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jin-Fang Song ◽  
Jie Zhang ◽  
Ming-Zhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
...  

AbstractGenetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case–control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P < 0.05). Post 8-week of treatment, newly diagnosed T2DM patients showed a less reduction in fasting plasma glucose levels and less increase in the carriers of genotype CG + GG at rs10830963 when compared with the CC genotype (P < 0.05). MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.Trial registration Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Di Xiao ◽  
Yu Guo ◽  
Xi Li ◽  
Ji-Ye Yin ◽  
Wei Zheng ◽  
...  

Background. We aimed to investigate the distributive characteristics ofSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients.Methods. The distributions ofSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy.Results. No significant difference was found between T2DM patients and healthy subjects inSLC22A1rs594709 andSLC47A1rs2289669 allele frequencies and genotype frequencies. After metformin treatment,SLC22A1rs594709 GG genotype patients showed a higher increase in FINS (p=0.015) and decrease in HOMA-IS (p=0.001) and QUICKI (p=0.002) than A allele carriers.SLC47A1rs2289669 GG genotype patients had a higher decrease in TChol (p=0.030) and LDL-C (p=0.049) than A allele carriers. AmongSLC22A1rs594709 AA genotype, patients withSLC47A1rs2289669 AA genotype showed a higher decrease in FBG (p=0.015), PINS (p=0.041), and HOMA-IR (p=0.014) than G allele carriers. However, amongSLC22A1rs594709 G allele carriers,SLC47A1rs2289669 AA genotype patients showed a higher decrease in TChol (p=0.013) than G allele carriers.Conclusion. Our data suggest thatSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tao Wang ◽  
Jin-Fang Song ◽  
Xue-Yan Zhou ◽  
Cheng-Lin Li ◽  
Xiao-Xing Yin ◽  
...  

Abstract Background Genetic 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). Methods Sixty 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. Results After 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). Conclusions The PPARD rs2016520 and NOS1AP rs12742393 polymorphisms were associated with nateglinide monotherapy efficacy in Chinese patients with newly diagnosed T2DM. Trial registration Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.


2020 ◽  
Author(s):  
Xingxing He ◽  
Jiaorong Su ◽  
Xiaojing Ma ◽  
Jingyi Lu ◽  
Yufei Wang ◽  
...  

Abstract Background: Recent studies noted that circulating growth differentiation factor 15 (GDF15) were closely related to metabolic states. The study aimed to explore the changes of GDF15 levels and their influencing factors after 4 weeks of lifestyle intervention (LI) or LI combined with breakfast meal replacement (LI+MR) in newly diagnosed type 2 diabetes patients. Methods: A total of 84 patients with available serum samples at both baseline and Week 4 were enrolled in this biomarker substudy. All subjects underwent a 2-hour 75g oral glucose tolerance test at baseline and Week 4. Serum GDF15 levels were determined by a sandwich enzyme-linked immunosorbent assay. Results: After 4-weeks of LI, GDF15 levels overall significantly decreased compared with baseline (P<0.05). ∆GDF15 levels were significantly and negatively associated with baseline GDF15 levels (r=–0.450, P<0.001). The optimal cut-off point of baseline GDF15 levels for predicting a GDF15 decrease after 4-weeks of LI was 904.57 pg/ml, with an area under curve of 0.699. Based on the cut-off point of 900 pg/ml, patients with baseline GDF15 ≥900 pg/ml had significantly decreased GDF15 levels after LI, while those <900 pg/ml had no significant changes. Regression models showed that baseline GDF15 level was an independent positive factor for the improvement of fasting plasma glucose and homeostasis model assessment for insulin resistance only in patients with baseline GDF15 levels ≥900 pg/ml. Conclusions: LI led to significantly decreased GDF15 levels among patients with newly diagnosed type 2 diabetes and its effect was more significant among patients with baseline GDF15 levels ≥900 pg/ml.Trial registration: ClinicalTrials.gov, NCT02248714. Registered 25 September 2014 - Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02248714?term=NCT02248714&draw=2&rank=1


2011 ◽  
Vol 165 (4) ◽  
pp. 597-601 ◽  
Author(s):  
Dandong Wu ◽  
Ling Li ◽  
Mengliu Yang ◽  
Hua Liu ◽  
Gangyi Yang

ObjectiveSecreted protein acidic and rich in cysteine (SPARC) also known as BM-40 which has been studied in various pathological conditions, has recently been suggested as a key player in the pathology of obesity and type 2 diabetes mellitus (T2DM). However, there are few studies on putative pathophysiologic roles of SPARC in glucose metabolism. The aim of this study was to determine whether plasma SPARC concentrations were altered in subjects with different glucose metabolic conditions and to investigate the affecting factors.Design and methodsIn this study, 54 newly diagnosed T2DM subjects, 53 subjects with impaired glucose regulation (IGR), and 53 normal subjects (body mass index (BMI): 24.98±3.75 vs 24.70±2.78 and 24.53±3.66 kg/m2, P>0.05) were enrolled. Plasma SPARC levels were measured with an ELISA under overnight fasting conditions. The relationships between plasma SPARC and several metabolic factors, such as BMI, blood lipids, blood glucose, plasma insulin levels, and other factors were also assessed.ResultsSPARC levels were higher in subjects with T2DM compared with IGR and control subjects (16.74±6.99 vs 14.04±8.03 μg/l, P<0.05 and 16.74±6.99 vs 11.72±4.47 μg/l, P<0.01). However, there was no difference in plasma SPARC levels between IGR subjects and the controls. Plasma SPARC levels correlated positively with BMI, the percentage of fat, triglyceride, fasting plasma insulin, 2 h plasma insulin after a glucose load, and the homeostasis model assessment of insulin resistance in simple regression analysis.ConclusionThe present work indicates a potential link between SPARC and the pathogenesis of T2DM.


2017 ◽  
Vol 14 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Wen-Jia Chen ◽  
Yue Liu ◽  
Yu-Bin Sui ◽  
Bo Zhang ◽  
Xiao-Hui Zhang ◽  
...  

Background: Musclin is a newly identified skeletal muscle–derived secretory factor, which has been recently characterized as a stimulator that induces insulin resistance in mice. However, the pathophysiological role of musclin in humans remains poorly understood. The aim of this study was to explore the potential correlations between musclin plasma levels and various metabolic parameters in patients with type 2 diabetes mellitus. Materials and methods: In this hospital-based study, plasma samples were collected from the enrolled individuals, including 38 newly diagnosed, treatment-naive type 2 diabetes mellitus patients and 41 age- and gender-matched control subjects. Plasma musclin levels were examined by radioimmunoassay. Results: Compared with the control group, musclin plasma levels were significantly higher in untreated type 2 diabetes mellitus patients. Musclin levels in the plasma of newly diagnosed type 2 diabetes mellitus patients were positively correlated with fasting plasma glucose, haemoglobin A1c, serum insulin, triglycerides and homeostasis model assessment of insulin resistance. Furthermore, multivariate logistic regression analysis showed that the level of musclin was associated with the presence of type 2 diabetes mellitus. Receiver operating characteristic curve analysis yielded an area under the curve for musclin of 0.718 in type 2 diabetes mellitus. Conclusion: The circulating concentration of musclin was significantly increased in type 2 diabetes mellitus patients. Our results suggest that musclin has a strong relationship with insulin resistance in type 2 diabetes mellitus.


2020 ◽  
Author(s):  
Rebiya Nuli ◽  
Jiaoyu Shan ◽  
Bing Zhang ◽  
Rui Li ◽  
Yaqun Guan

Abstract Background: Type 2 diabetes (T2DM) is a top risk factor for health in China. Gut microbiota, genetic factors and lipids metabolism play important role in development of T2DM. In this study, we investigated the relationship between the gut microbiota and omentin-1 gene polymorphism to explore the interaction between host gene and gut microbiota in Uyghur T2DM. Methods: A total of 98 newly diagnosed Uyghur T2DM patients and 99 healthy normal controls (NC) enrolled into this study according to inclusion criteria. The total DNAs was extracted from the fecal microbiota. Abundance of the Lactobacillus genus, Bacteroides thetaiotaomicron and Clostridium in the gut microbiota was determined with 16S rDNA gene Real-time fluorescence quantitative PCR amplification. PCR-PFLP was applied to determine the genotypes of Val109Asp variant (rs2274907) in the Omentin-1 gene. And the relationship between rs2274907 and gut microbiota was assessed. Results: There were no significant differences of the Val109Asp variant (rs2274907) between T2DM and NC group. The abundance of Lactobacillus genus and Clostridium genus was lower in newly diagnosed T2DM group than in the NC group (P<0.05). Serum insulin, LDL-C, the abundances of Lactobacillus genus and Clostridium genus were the risk factors of T2DM. (OR=1.094 95%CI 1.014-1.180), (OR=3.868 95%CI 1.250-11.971), (OR=0.288 95%CI 0.145-0.571), (OR=0.044 95%CI 0.012-0.154). Conclusions: The abundance of Lactobacillus and Clostridium genus may be related to the pathogenesis of new-onset T2DM in Uyghur population, the mechanism of which needs to be further studied. The interactive relationship between the gut microbiota and omentin-1 gene polymorphism in newly diagnosed T2DM was not observed in this study.


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