The Biostatistics Center, The George Washington University, 6110 Executive Boulevard, Rockville, MD, 20852, USA.
Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
Diabetologia. 2017 Oct;60(10):2084-2091. doi: 10.1007/s00125-017-4374-4. Epub 2017 Jul 16.
AIMS/HYPOTHESIS: Chronic hyperglycaemia, as measured by HbA levels, is a major risk factor for atherosclerosis and cardiovascular disease (CVD) in type 1 diabetes. Our aim was to describe the degree to which the effect of HbA on the risk of CVD is mediated by its effect on traditional risk factors over time, and how these mediation pathways change over time.
The DCCT and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), followed 1441 participants for a mean of 27 years, with periodic measurement of HbA and risk factors over time. We assessed the proportion of the HbA effect on risk of CVD that was mediated through its effects on systolic BP (SBP), pulse rate, triacylglycerols and LDL-cholesterol (LDLc) levels, and how the proportion mediated changed over time.
The association of HbA with CVD outcomes was stable over time, while that of traditional risk factors (SBP, pulse rate, triacylglycerols and LDLc) increased. At 10 years of follow-up, the effect of HbA on 10 year CVD risk was minimally mediated by SBP (2.7%), increasing to 26% at 20 years. Likewise, from 10 year follow-up to 20 year follow-up, the proportion of HbA effect mediated through pulse rate increased from 6.3% to 29.3%, through triacylglycerols from 2.2% to 22.4%, and through LDLc from 9.2% to 30.7%.
CONCLUSIONS/INTERPRETATION: As participants age, the predictive association of mean HbA on subsequent CVD events is increasingly mediated by its effect on standard risk factors. Thus, management of traditional non-glycaemic CVD risk factors may have increasing benefits in an ageing type 1 diabetes population with longstanding hyperglycaemia.
ClinicalTrials.gov NCT00360893 and NCT00360815.
目的/假设：慢性高血糖（通过 HbA 水平测量）是 1 型糖尿病患者发生动脉粥样硬化和心血管疾病（CVD）的主要危险因素。我们的目的是描述 HbA 对 CVD 风险的影响在多大程度上通过其对传统危险因素的影响随时间而变化，以及这些中介途径如何随时间而变化。
糖尿病控制与并发症试验（DCCT）及其观察性随访研究——糖尿病并发症流行病学（EDIC），对 1441 名参与者进行了平均 27 年的随访，定期测量 HbA 和随时间变化的危险因素。我们评估了 HbA 对 CVD 风险的影响通过其对收缩压（SBP）、脉搏率、三酰甘油和 LDL 胆固醇（LDLc）水平的影响而发生的中介比例，以及这种中介比例随时间的变化。
HbA 与 CVD 结局的关联在整个随访期间保持稳定，而传统危险因素（SBP、脉搏率、三酰甘油和 LDLc）的关联则增加。在 10 年随访时，HbA 对 10 年 CVD 风险的影响仅通过 SBP 进行中介（2.7%），在 20 年随访时增加到 26%。同样，从 10 年随访到 20 年随访，HbA 效应通过脉搏率进行中介的比例从 6.3%增加到 29.3%，通过三酰甘油从 2.2%增加到 22.4%，通过 LDLc 从 9.2%增加到 30.7%。
结论/解释：随着参与者年龄的增长，平均 HbA 对随后 CVD 事件的预测关联越来越受到其对标准危险因素的影响。因此，在长期高血糖的 1 型糖尿病人群中，管理传统的非血糖性 CVD 危险因素可能会带来越来越多的益处。
ClinicalTrials.gov NCT00360893 和 NCT00360815。
