Dalgård Christine, Möller Soren, Kyvik Kirsten O
Department of Public Health, Environmental Medicine and The Danish Twin Registry, University of Southern Denmark, Odense C, Denmark.
Odense Patient Data Explorative Network (OPEN), Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense C, Denmark.
Twin Res Hum Genet. 2020 Feb;23(1):39-44. doi: 10.1017/thg.2020.3. Epub 2020 Feb 21.
Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable.
2型糖尿病由遗传和环境因素共同引起,可通过口服葡萄糖耐量试验(OGTT)进行诊断。最近的研究表明,OGTT期间血糖曲线存在与心脏代谢风险特征相关的特定模式。由于遗传和环境对血糖曲线模式的相对影响尚不清楚,我们旨在研究这些模式的遗传力。我们研究了丹麦GEMINAKAR队列中年龄在18 - 67岁之间、基线时无糖尿病的双胞胎;在2小时的OGTT期间测量了三次血糖浓度。使用潜在类别混合效应模型检查OGTT期间血糖反应的异质性,并通过贝叶斯信息准则评估拟合优度。基于线性结构方程,使用定量遗传模型估计对曲线模式的遗传影响。总体而言,1455对双胞胎(41%为同卵双胞胎)有来自OGTT的有效血糖浓度测量值,并识别出四种具有不同血糖反应模式的潜在类别。统计建模表明,属于特定类别的遗传影响存在,遗传力估计在45%至67%之间。在约12年的随访期间,这四类与2型糖尿病的不同发病率相关。因此,与2型糖尿病风险相关的血糖反应曲线模式似乎具有中度至高度遗传性。