Claussen Anetta, Møller Jonas B, Kristensen Niels R, Klim Søren, Kjellsson Maria C, Ingwersen Steen H, Karlsson Mats O
Current address: Certara Strategic Consulting, Basel, Switzerland; Quantitative Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
New Product Planning, Novo Nordisk A/S, Søborg, Denmark.
Eur J Pharm Sci. 2017 Jun 15;104:417-423. doi: 10.1016/j.ejps.2017.04.006. Epub 2017 Apr 13.
Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012).
To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model.
Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, BMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component.
Participants included 47% females and 20% above 65years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races.
Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model.
The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship.
Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials.
多项研究表明，平均血浆葡萄糖（MPG）与糖化血红蛋白（HbA1c）之间的关系可能因人群而异。尤其是种族因素此前被认为会使稳态下将MPG与HbA1c联系起来的回归线发生偏移（赫尔曼和科恩，2012年）。
在纵向模型中评估人口统计学和疾病进展相关协变量对估计的线性MPG-HbA1c关系截距的影响。
来自16项2型糖尿病晚期试验的纵向患者水平数据，共8927名受试者，用于研究MPG与HbA1c关系的协变量。分析的协变量包括年龄组、体重指数、性别、种族、糖尿病病程和试验前治疗。通过估计试验间变异性成分来考虑试验之间的差异。
参与者中47%为女性，20%年龄在65岁以上。77%为白种人，9%为亚洲人，5%为黑人，其余9%作为其他种族一起分析。
使用纵向模型确定由于上述协变量导致的MPG-HbA1c关系截距变化的估计值。
分析表明，试验前使用胰岛素治疗的影响最为显著，在给定的MPG水平下，HbA1c升高0.34%。然而，种族、糖尿病病程和年龄组也对MPG-HbA1c关系有影响。
我们的分析表明，MPG与HbA1c之间的关系对协变量相对不敏感，但在不同人群中存在微小差异，在临床试验中基于MPG测量预测HbA1c反应时，可能需要考虑这些差异。
