无糖尿病个体中TCF7L2基因rs7903146多态性与连续血糖监测得出的参数之间的关联
Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes.
作者信息
van der Kroef Sabrina, Noordam Raymond, Deelen Joris, Akintola Abimbola A, Jansen Steffy W M, Postmus Iris, Wijsman Carolien A, Beekman Marian, Mooijaart Simon P, Slagboom P Eline, van Heemst Diana
机构信息
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
出版信息
PLoS One. 2016 Feb 25;11(2):e0149992. doi: 10.1371/journal.pone.0149992. eCollection 2016.
BACKGROUND
The rs7903146-T allele in the transcription factor 7-like 2 (TCF7L2) gene has been associated with impaired pancreatic insulin secretion, enhanced liver glucose production, and an increased risk of type 2 diabetes. Nevertheless, the impact of rs7903146 on daily glucose trajectories remains unclear. Continuous glucose monitoring (CGM) can estimate glycemia and glycemic variability based on consecutive glucose measurements collected over several days. The purpose of the present study was to investigate the associations of rs7903146 with glycemia and glycemic variability in middle-aged participants without diabetes.
METHODS
Complete data from 235 participants without diabetes from the Leiden Longevity Study were available. Participants were divided into two groups based on rs7903146 genotype; rs7903146-CC genotype carriers (N = 123) and rs7903146-CT/TT genotype carriers (N = 112). Validated parameters of glycemia (e.g., mean 24h glucose level) and glycemic variability (e.g., 24h standard deviation) were derived from data collected with a CGM system for a 72-hour period.
RESULTS
The study population was on average 64.7 years old (standard deviation = 5.9) and composed of 49.8% of women. Compared with rs7903146-CC carriers, rs7903146-CT/TT carriers exhibited a trend towards a higher mean 24-hour glucose level (5.21 versus 5.32 mmol/L; p-value = 0.15) and a significantly higher mean nocturnal glucose (3:00am- 6:00am; 4.48 versus 4.67 mmol/L; p-value = 0.03) that was explained for 34.6% by body weight and percentage body fat. No differences in measures of glycemic variability between the genotype groups were observed.
CONCLUSION
Despite limited sample size, our study indicates that the rs7903146-T allele in TCF7L2 was associated with a higher mean nocturnal glucose dependent on body composition, which might suggest that rs7902146 affects liver-specific aspects of glucose metabolism.
背景
转录因子7样2（TCF7L2）基因中的rs7903146 - T等位基因与胰腺胰岛素分泌受损、肝脏葡萄糖生成增强以及2型糖尿病风险增加有关。然而，rs7903146对每日血糖轨迹的影响仍不清楚。连续血糖监测（CGM）可以根据数天内收集的连续血糖测量值来估计血糖水平和血糖变异性。本研究的目的是调查rs7903146与无糖尿病中年参与者的血糖水平及血糖变异性之间的关联。
方法
从莱顿长寿研究中获取了235名无糖尿病参与者的完整数据。根据rs7903146基因型将参与者分为两组；rs7903146 - CC基因型携带者（N = 123）和rs7903146 - CT/TT基因型携带者（N = 112）。血糖水平（如24小时平均血糖水平）和血糖变异性（如24小时标准差）的有效参数来自于用CGM系统收集的72小时数据。
结果
研究人群平均年龄为64.7岁（标准差 = 5.9），女性占49.8%。与rs7903146 - CC携带者相比，rs7903146 - CT/TT携带者的24小时平均血糖水平有升高趋势（5.21对5.32 mmol/L；p值 = 0.15），夜间平均血糖（凌晨3:00 - 6:00；4.48对4.67 mmol/L；p值 = 0.03）显著更高，体重和体脂百分比可解释其中34.6%的差异。未观察到基因型组之间血糖变异性指标的差异。
结论
尽管样本量有限，但我们的研究表明，TCF7L2基因中的rs7903146 - T等位基因与依赖于身体组成的较高夜间平均血糖有关，这可能表明rs7902146影响肝脏特异性的葡萄糖代谢方面。
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