2型糖尿病患者强化血糖控制与血管转归

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

作者信息

Patel Anushka, MacMahon Stephen, Chalmers John, Neal Bruce, Billot Laurent, Woodward Mark, Marre Michel, Cooper Mark, Glasziou Paul, Grobbee Diederick, Hamet Pavel, Harrap Stephen, Heller Simon, Liu Lisheng, Mancia Giuseppe, Mogensen Carl Erik, Pan Changyu, Poulter Neil, Rodgers Anthony, Williams Bryan, Bompoint Severine, de Galan Bastiaan E, Joshi Rohina, Travert Florence

出版信息

N Engl J Med. 2008 Jun 12;358(24):2560-72. doi: 10.1056/NEJMoa0802987. Epub 2008 Jun 6.

DOI:10.1056/NEJMoa0802987

PMID:18539916

Abstract

BACKGROUND

In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.

METHODS

We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately.

RESULTS

After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).

CONCLUSIONS

A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)

摘要

背景

在2型糖尿病患者中，强化血糖控制对血管结局的影响仍不确定。

方法

我们将11140例2型糖尿病患者随机分为两组，分别接受标准血糖控制或强化血糖控制。强化血糖控制定义为使用格列齐特（缓释片）并根据需要加用其他药物，以使糖化血红蛋白值达到6.5%或更低。主要终点是主要大血管事件（心血管原因导致的死亡、非致死性心肌梗死或非致死性卒中）和主要微血管事件（新发或恶化的肾病或视网膜病变）的复合终点，对其进行联合评估和单独评估。

结果

经过中位5年的随访，强化治疗组的平均糖化血红蛋白水平（6.5%）低于标准治疗组（7.3%）。强化治疗降低了主要大血管和微血管事件的联合发生率（18.1%，标准治疗组为20.0%；风险比，0.90；95%置信区间[CI]，0.82至0.98；P = 0.01），以及主要微血管事件的发生率（9.4%对10.9%；风险比，0.86；95%CI，0.77至0.97；P = 0.01），主要原因是肾病发生率降低（4.1%对5.2%；风险比，0.79；95%CI，0.66至0.93；P = 0.006），而对视网膜病变无显著影响（P = 0.50）。血糖控制类型对主要大血管事件（强化治疗的风险比，0.94；95%CI，0.84至1.06；P = 0.32）、心血管原因导致死亡（强化治疗的风险比，0.88；95%CI，0.74至1.04；P = 0.12）或任何原因导致死亡（强化治疗的风险比，0.93；95%CI，0.83至1.06；P = 0.28）均无显著影响。严重低血糖虽然不常见，但在强化治疗组中更常见（2.7%，标准治疗组为1.5%；风险比，1.86；95%CI，1.42至2.40；P<0.001）。