寻找在治疗相关严重低血糖事件罕见发生的2型糖尿病患者中将死亡率降至最低的糖化血红蛋白目标——J-DOIT3随机对照试验的流行病学分析。
完整摘要 · 中文译文
目的：近年来，随着糖尿病治疗手段的重大变化，糖尿病患者药物治疗相关的低血糖事件，尤其是严重低血糖事件的发生率已显著下降。我们因此受到启发，评估在此背景下，与糖尿病大血管并发症风险最小化相关的各项干预目标阈值，尤其是血糖控制目标。 方法：在我们此前开展的日本糖尿病优化综合治疗研究（针对心血管疾病的3个主要危险因素，J-DOIT3）中，我们招募了2542名受试者，并将其分配至常规治疗组（n = 1271）和强化治疗组（n = 1271；此后有2名不符合条件的受试者被从所有分析中剔除），两组的严重低血糖事件发生率均较低（中位随访8.5年期间，强化治疗组7例，常规治疗组4例）。为实现本研究的目的，我们以J-DOIT3研究基线后1年作为标志性时间点，进行了一项标志性分析。随后，使用糖化血红蛋白（HbA1c）、收缩压、LDL-胆固醇和HDL-胆固醇水平的更新平均值，我们确定了与各结局（包括主要结局和心血管结局）最低风险比相关的各项变量的最佳水平。 结果：在血糖控制方面，我们的结果显示，与最低风险相关的糖化血红蛋白不存在明确的下限阈值。 心肌梗死或全因死亡风险的k值；对于其他危险因素，将低密度脂蛋白胆固醇水平维持在80 mg/dL以下以尽可能降低卒中风险可能是一个重要的治疗目标。 结论：本分析提示，对于严重低血糖事件发生率较低的糖尿病参与者，为尽可能降低全因死亡风险，HbA1c的治疗目标可能应低于6.5%（临床试验注册号：NCT00300976）。
完整摘要 · 英文原文
OBJECTIVES: In recent years, with the considerable changes in the therapeutic armamentarium for diabetes, the incidence of hypoglycemia events, especially severe hypoglycemia events, associated with drug treatment in people with diabetes has markedly decreased. We were prompted to evaluate the threshold for each intervention target, especially glycemic control, associated with a minimized risk of the macrovascular complications of diabetes in this setting. METHODS: In the Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3) conducted by us previously, we recruited 2542 participants and assigned them to a conventional therapy group (n = 1271) and an intensive therapy group (n = 1271; two ineligible participants were removed from all analyses afterwards), and the incidence of severe hypoglycemia events was low in both groups (7 in the intensive therapy group and 4 in the conventional therapy group during a median 8.5 years' follow-up). Towards the objective of this study, we undertook a landmark analysis with a landmark time-point of 1 year after the baseline of the J-DOIT3 study. Then, using the updated mean values of the glycated hemoglobin (HbA1c), systolic blood pressure, and LDL-cholesterol and HDL-cholesterol levels, we determined the optimal levels of each of these variables associated with the lowest hazard ratios for outcomes, including the primary and cardiovascular outcomes. RESULTS: For glycemic control, our results revealed no clear lower threshold of the glycated hemoglobin associated with the lowest risk of myocardial infarction or all-cause mortality; for other risk factors, it might be an important treatment target to maintain the LDL-cholesterol levels at below 80 mg/dL to minimize the risk of stroke. CONCLUSIONS: The present analysis suggested that the treatment target for HbA1c to minimize the risk of all-cause mortality in participants with diabetes with a low incidence of severe hypoglycemia episodes could be < 6.5% (ClinicalTrials.gov, number NCT00300976).