JCEM：T2DM胰岛素治疗增加糖尿病相关并发症

胰岛素在2型糖尿病（T2DM）治疗中的安全性最近遭受质疑。为了描述2型糖尿病患者降血糖治疗相关不良事件的风险。来自英国加的夫药物研究中心Craig J Currie教授及其团队进行了一项研究，该研究发现，在2型糖尿病患者，外源性胰岛素治疗与糖尿病相关并发症、癌症和全因死亡率风险增加有关。该研究结果在线发表在2013年2月的《临床内分泌代谢杂志》（The journal of clinical endocrinology & metabolism）上。

该研究是一项回顾性队列研究，使用的数据来自2000–2010年英国综合实践研究数据库。患者包括84622例初级治疗的2型糖尿病患者，使用下面五种降糖方案中的一种：二甲双胍单药治疗、磺脲类药物弹药治疗、胰岛素单药治疗、二甲双胍加磺脲类药物联合治疗、以及胰岛素加二甲双胍联合治疗。测量首次主要不良心脏事件、首次癌症、或者死亡率。次要结局指标包括那些个体成分和心血管并发症。

该研究结果表明，在同一模型中，使用二甲双胍单药治疗作为对照，磺脲类药物单药治疗（1.436,95%可信区间[CI]1.354–1.523）、胰岛素单药治疗（1.808,95%CI 1.630–2.005）、以及胰岛素加二甲双胍联合治疗（1.309,95%CI 1.150–1.491）主要终点的校正风险比（aHR）显著增加。在糖化血红蛋白/发病率亚组，胰岛素单药治疗患者主要结局指标的aHRs从1.469（95%CI 0.978–2.206）到2.644（95%CI 1.896–3.687）。胰岛素单药治疗的所有次要结局指标的aHRs增加：心肌梗死（1.954,95%CI 1.479–2.583）、主要不良心脏事件（1.736,95%CI 1.441–2.092）、中风（1.432,95%CI 1.159–1.771）、肾脏并发症（3.504,95%CI 2.718–4.518）、神经病变（2.146,95%CI 1.832–2.514）、眼部并发症（1.171,95%CI 1.057–1.298）、癌症（1.437,95%CI 1.234–1.674）、全因死亡率（2.197,95%CI 1.983–2.434）。当直接比较时，胰岛素单药治疗主要终点和全因死亡率的aHRs比其他所有方案更高。

该研究发现，在2型糖尿病患者，外源性胰岛素治疗与糖尿病相关并发症、癌症和全因死亡率风险增加有关。在解释这些结果时，治疗组间基线特征的差异应该被考虑到。

Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes.
CONTEXT
The safety of insulin in the treatment of type 2 diabetes mellitus (T2DM) has recently undergone scrutiny.
OBJECTIVE
The objective of the study was to characterize the risk of adverse events associated with glucose-lowering therapies in people with T2DM.
DESIGN AND SETTING
This was a retrospective cohort study using data from the UK General Practice Research Database, 2000-2010.
PATIENTS
Patients comprised 84 622 primary care patients with T2DM treated with one of five glucose-lowering regimens: metformin monotherapy, sulfonylurea monotherapy, insulin monotherapy, metformin plus sulfonylurea combination therapy, and insulin plus metformin combination therapy. There were 105 123 exposure periods.
MAIN OUTCOME MEASURES
The risk of the first major adverse cardiac event, first cancer, or mortality was measured. Secondary outcomes included these individual constituents and microvascular complications.
RESULTS
In the same model, and using metformin monotherapy as the referent, the adjusted hazard ratio (aHR) for the primary end point was significantly increased for sulfonylurea monotherapy (1.436, 95% confidence interval [CI] 1.354-1.523), insulin monotherapy (1.808, 95% CI 1.630-2.005), and insulin plus metformin (1.309, 95% CI 1.150-1.491). In glycosylated hemoglobin/morbidity subgroups, patients treated with insulin monotherapy had aHRs for the primary outcome ranging from 1.469 (95% CI 0.978-2.206) to 2.644 (95% CI 1.896-3.687). For all secondary outcomes, insulin monotherapy had increased aHRs: myocardial infarction (1.954, 95% CI 1.479-2.583), major adverse cardiac events (1.736, 95% CI 1.441-2.092), stroke (1.432, 95% CI 1.159-1.771), renal complications (3.504, 95% CI 2.718-4.518), neuropathy (2.146, 95% CI 1.832-2.514), eye complications (1.171, 95% CI 1.057-1.298), cancer (1.437, 95% CI 1.234-1.674), or all-cause mortality (2.197, 95% CI 1.983-2.434). When compared directly, aHRs were higher for insulin monotherapy vs all other regimens for the primary end point and all-cause mortality.
CONCLUSIONS
In people with T2DM, exogenous insulin therapy was associated with an increased risk of diabetes-related complications, cancer, and all-cause mortality. Differences in baseline characteristics between treatment groups should be considered when interpreting these results.