Department of Diabetes and Endocrinology, Scripps Clinic Torrey Pines, San Diego, California 92037, USA.
Clin Ther. 2011 Jun;33(6):665-78. doi: 10.1016/j.clinthera.2011.04.025.
Type 2 diabetes mellitus (T2DM) results in significant morbidity and mortality. Results of recent randomized controlled trials demonstrated the ability of early and intensive therapy to reduce the risk of microvascular complications. However, controversy surrounds the ability of such therapy to reduce the risk for macrovascular complications.
This article reviews results from recent clinical trials in patients with T2DM as well as extended follow-up of earlier trials to determine if early, intensive, and individualized therapy aimed at the underlying pathogenesis of the disease could decrease the risk for long-term complications, including cardiovascular disease (CVD).
Information was obtained by a search of the PUBMED and EMBASE databases using the search terms type 2 diabetes mellitus, glycosylated hemoglobin, pathophysiology of type 2 diabetes, glycemic control, early intervention, multifactorial intervention, cardiovascular disease, β-cell function, and antidiabetes therapy for the period between 1995 and 2010. Articles dealing with outcomes trials, impact of therapy on microvascular and macrovascular complications, effects of therapeutic agents on the pathophysiology of T2DM, and the impact of agents on CV risk factors were then preferentially selected for in-depth review.
Large-scale clinical trials in patients with T2DM, although largely negative at 5 years for macrovascular end points, suggested benefit for patients with a shorter duration of T2DM (ie, <10 years) and still supported a treatment strategy of early, intensive, and individualized therapy to prevent long-term complications of the disease. In Steno-2, after 13 years of follow-up, early, intensive, multifactorial therapy was associated with a 56% lower risk of all-cause death (P = 0.02) and a 57% lower risk of death from CVD (P = 0.04). In the 10-year follow-up to the United Kingdom Prospective Diabetes Study, intensive therapy was associated with a significant 15% reduction in the risk of myocardial infarction (P = 0.01) and a significant 13% reduction in the risk of death from any cause (P = 0.007). Therapy should be aimed at correcting underlying pathophysiologic defects, including β-cell failure and insulin resistance, and should also correct underlying risk factors for CVD whenever possible.
Early and intensive antidiabetes treatment was recommended in patients with T2DM, particularly those with a shorter duration of disease and without a history of CVD. The goal was to safely lower glycosylated hemoglobin to <7%, therefore providing beneficial effects on the risk for complications. Hypoglycemia should be avoided. In addition, less aggressive treatment might be suitable for older patients with longstanding diabetes and a history of CVD events. Clinical trial results also provided support for a second important aspect of individualized treatment for patients with T2DM-multifactorial intervention aimed at controlling CVD risk factors.
2 型糖尿病（T2DM）导致严重的发病率和死亡率。最近的随机对照试验结果表明，早期和强化治疗能够降低微血管并发症的风险。然而，这种治疗是否能够降低大血管并发症的风险仍存在争议。
本文综述了 T2DM 患者最近的临床试验结果以及早期试验的延长随访结果，以确定针对疾病潜在发病机制的早期、强化和个体化治疗是否能够降低长期并发症（包括心血管疾病[CVD]）的风险。
通过在 PUBMED 和 EMBASE 数据库中使用“type 2 diabetes mellitus”、“glycosylated hemoglobin”、“pathophysiology of type 2 diabetes”、“glycemic control”、“early intervention”、“multifactorial intervention”、“cardiovascular disease”、“β-cell function”和“antidiabetes therapy”等关键词进行检索，获取信息。然后优先选择涉及结局试验、治疗对微血管和大血管并发症的影响、治疗药物对 T2DM 病理生理学的影响以及药物对心血管危险因素的影响的文章进行深入综述。
尽管在 5 年时大型 T2DM 临床试验在大血管终点方面大多为阴性，但对于病程较短（<10 年）的患者仍提示治疗获益，并仍支持早期、强化和个体化治疗策略，以预防疾病的长期并发症。在 Steno-2 中，经过 13 年的随访，早期、强化、多因素治疗可使全因死亡风险降低 56%（P=0.02），CVD 死亡风险降低 57%（P=0.04）。在英国前瞻性糖尿病研究的 10 年随访中，强化治疗可使心肌梗死风险降低 15%（P=0.01），任何原因导致的死亡风险降低 13%（P=0.007）。治疗应旨在纠正潜在的病理生理缺陷，包括β细胞衰竭和胰岛素抵抗，并尽可能纠正潜在的 CVD 危险因素。
建议 T2DM 患者（特别是病程较短且无 CVD 病史的患者）进行早期和强化抗糖尿病治疗。目标是安全地将糖化血红蛋白降低至<7%，从而对并发症风险产生有益影响。应避免低血糖。此外，对于长期患有糖尿病和 CVD 事件史的老年患者，可能需要采用不那么激进的治疗方法。临床试验结果也为 T2DM 患者个体化治疗的另一个重要方面提供了支持，即针对 CVD 危险因素的多因素干预。
