Longitudinal profiling and tracking stability in the Singapore study of macro-angiopathy and microvascular reactivity in type 2 diabetes cohort.

Serena Low, Huili Zheng, Jian-Jun Liu, Angela Moh, Keven Ang, Wern Ee Tang, Ziliang Lim, Tavintharan Subramaniam, Chee Fang Sum, Su Chi Lim
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Abstract

Introduction: The Singapore Study of Macro-Angiopathy and microvascular Reactivity in Type 2 Diabetes (SMART2D) is a prospective cohort study which was started in 2011 to investigate the effect of risk factors on vascular function and diabetes-related complications in Asians. We aimed to compare the longitudinal change in risk factors by accounting for batch effect and assess the tracking stability of risk factors over time in patients recruited for SMART2D. In this study, we (1) described batch effect and its extent across a heterogenous range of longitudinal data parameters; (2) mitigated batch effect through statistical approach; and (3) assessed the tracking stability of the risk factors over time.

Methods: A total of 2258 patients with type 2 diabetes mellitus (T2DM) were recruited at baseline. The study adopted a three-wave longitudinal design with intervals of 3 years between consecutive waves. The changes in a few selected risk factors were assessed after calibration, assuming patients with similar demographic and anthropometry profile had similar physiology. The tracking pattern of the risk factors was determined with stability coefficients derived from generalised estimating equations.

Results: The medians of the longitudinal differences in risk factors between the waves were mostly modest at <10%. Larger increases in augmentation index (AI), aortic systolic blood pressure (BP) and aortic mean BP were consistently observed after calibration. The medians of the longitudinal differences in AI, aortic systolic BP and aortic mean BP between the waves were <2% before calibration, but increased slightly to <5% after calibration. Most of the risk factors had moderate to high tracking stability. Muscle mass and serum creatinine were among those with relatively high tracking stability.

Conclusions: The longitudinal differences in parameters between the waves were overall modest after calibration, suggesting that calibration may attenuate longitudinal differences inflated by non-biological factors such as systematic drift due to batch effect. Changes of the hemodynamic parameters are robust over time and not entirely attributable to age. Our study also demonstrated moderate to high tracking stability for most of the parameters.

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2型糖尿病队列大血管病变和微血管反应性新加坡研究的纵向分析和跟踪稳定性。
新加坡2型糖尿病大血管病变和微血管反应性研究(SMART2D)是一项于2011年启动的前瞻性队列研究,旨在研究亚洲人血管功能和糖尿病相关并发症的危险因素的影响。我们的目的是通过考虑批量效应来比较风险因素的纵向变化,并评估SMART2D招募的患者中风险因素随时间的跟踪稳定性。在本研究中,我们(1)描述了批效应及其在纵向数据参数异质范围内的程度;(2)通过统计方法缓解批量效应;(3)评估风险因素随时间的跟踪稳定性。方法:在基线时共招募2258例2型糖尿病(T2DM)患者。本研究采用三波纵向设计,连续波之间间隔3年。在校准后,假设具有相似人口统计学和人体测量特征的患者具有相似的生理特征,对一些选定的危险因素的变化进行评估。利用广义估计方程导出的稳定性系数确定了危险因素的跟踪模式。结果:各波间危险因素纵向差异的中位值在校正后大体适中,说明校正可能会减弱因批效应引起的系统漂移等非生物因素而放大的纵向差异。随着时间的推移,血流动力学参数的变化是稳健的,并不完全归因于年龄。我们的研究还证明了大多数参数的中等到高跟踪稳定性。
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