OBJECTIVE Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. RESEARCH DESIGN AND METHODS Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol. RESULTS While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82–1.32) or with (0.84, 0.63–1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29–0.76, Pinteraction = 0.01). CONCLUSIONS Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype.

中文翻译：

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结合珠蛋白表型和强化血糖控制可降低 2 型糖尿病患者的冠状动脉疾病风险：ADVANCE 研究

目的 强化血糖控制可减少糖尿病心血管风险控制行动 (ACCORD) 研究中具有触珠蛋白 (Hp)2-2 表型的参与者的冠状动脉疾病 (CAD) 事件，但不减少不具有 Hp2-2 表型的参与者的冠状动脉疾病 (CAD) 事件。目前尚不清楚这些结果是否以及如何在不同的人口/临床特征和治疗策略中转化。研究设计和方法 在糖尿病和血管疾病的作用：Preterax 和 Diamicron MR 对照评估 (ADVANCE) 生物标志物病例队列研究的可用样本中测量了触珠蛋白表型。使用加权多变量调整 Cox 回归模型来评估强化血糖控制（HbA1c 目标 ≤6.5%）与标准治疗（基于当地指南）与患有 (n = 1,327) 和不患有 (n = 2,077) Hp2-2 表型分别按性别、种族、既往心血管疾病 (CVD)、糖尿病病程和 HDL-胆固醇进行预先指定的分层。结果 虽然风险比 (HR) 处于假设的不同方向，但与标准治疗相比，强化血糖控制与没有（1.04，95% CI 0.82-1.32）或（0.84， 0.63–1.14，Pinteraction = 0.27) Hp2-2 整体表型。对于既往没有 CVD 的 Hp2-2 表型参与者，强化治疗与较低的 CAD 风险相关（0.47、0.29–0.76，Pinteraction = 0.01）。结论 我们的研究结果表明，强化血糖控制有助于预防具有 Hp2-2 表型且既往无 CVD 的 ADVANCE 参与者发生重大 CAD 事件，并且与我们的假设一致，即强化血糖控制可能对一部分患有 Hp2-2 表型的患者有益。 Hp2-2 表型。