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.

中文翻译：

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口服葡萄糖耐量试验曲线模式的遗传力

由遗传和环境因素引起的 2 型糖尿病可以使用口服葡萄糖耐量试验 (OGTT) 进行诊断。最近的研究表明，OGTT 期间葡萄糖曲线的特定模式与心脏代谢风险概况相关。由于遗传和环境影响对葡萄糖曲线模式的相对贡献是未知的，我们旨在研究这些模式的遗传力。我们研究了来自丹麦 GEMINAKAR 队列的双胞胎，年龄在 18-67 岁，并且在 1997-2000 年基线时没有糖尿病；在 2 小时 OGTT 期间测量了 3 次葡萄糖浓度。OGTT 期间葡萄糖反应的异质性用潜类混合效应模型进行检查，通过贝叶斯信息标准评估拟合优度。使用基于线性结构方程的定量遗传模型估计遗传对曲线模式的影响。总体而言，1455 对双胞胎（41% 为同卵双胞胎）具有从 OGTT 测量的有效葡萄糖浓度，并确定了具有不同葡萄糖反应模式的四个潜在类别。统计模型表明遗传影响是否属于特定类别，遗传率估计在 45% 到 67% 之间。在 12 年的随访中，这四个类别分别与不同的 2 型糖尿病发病率相关。因此，与 2 型糖尿病风险相关的葡萄糖反应曲线模式似乎具有中度至高度遗传性。并确定了四个具有不同葡萄糖反应模式的潜在类别。统计模型表明遗传影响是否属于特定类别，遗传率估计在 45% 到 67% 之间。在 12 年的随访中，这四个类别分别与不同的 2 型糖尿病发病率相关。因此，与 2 型糖尿病风险相关的葡萄糖反应曲线模式似乎具有中度至高度遗传性。并确定了四个具有不同葡萄糖反应模式的潜在类别。统计模型表明遗传影响是否属于特定类别，遗传率估计在 45% 到 67% 之间。在 12 年的随访中，这四个类别分别与不同的 2 型糖尿病发病率相关。因此，与 2 型糖尿病风险相关的葡萄糖反应曲线模式似乎具有中度至高度遗传性。