AIM：荟萃分析显示强化降糖对肾脏终点事件的预防效果不佳

《内科学文献》(Archives of Internal Medicine)5月28日在线发表的一项Meta分析的结果显示，与常规血糖控制相比，强化血糖控制对2型糖尿病患者的肾脏预后无明显影响。

美国糖尿病学会(ADA)及其他专家组建议通过强化血糖控制(定义为目标血红蛋白A1c水平低于7%)预防2型糖尿病患者发生肾脏疾病及其他微血管并发症，但目前尚不清楚强化血糖控制对临床肾脏终点事件的影响，因此美国耶鲁大学的Steven G. Coca及其同事对7项涉及28,065例2型糖尿病成人患者的研究进行了回顾分析。患者随访时间为2~15年，基线时的平均血清肌酐水平为0.9~1.0 mg/dl，平均2型糖尿病病程为7~12年。

结果显示，与常规血糖控制相比，强化血糖控制与微量白蛋白尿[危险比(RR)=0.86]和大量白蛋白尿(RR=0.74)风险降低相关。然而，强化血糖控制方案未能降低一些肾脏终点事件的风险，包括血清肌酐水平未翻倍(1.06)、终末期肾病(0.69)和肾病死亡(0.99)。

附加的Meta回归分析支持总体结果。在各项研究中，与常规血糖控制相比，强化血糖控制可降低发生微量白蛋白尿和大量白蛋白尿的风险，但未能改善肾脏预后。

该Meta分析的局限性在于所纳入的一些研究的预后数据非常不完整。强化血糖控制未能改善肾脏预后的原因可能在于启动强化血糖控制的时间过晚、强化血糖控制的维持时间不够长、HbA1c水平未降至正常，以及所达到的HbA1c水平未给患者带来额外益处等。另外，一些研究可能不足以发现肾脏预后方面的显著差异。

研究者总结指出，尽管存在上述局限性，但目前没有充分理由支持在疾病中期启动旨在预防肾功能衰竭的强化血糖控制方案。

HealthPartners研究基金会的Karen L. Margolis博士和Patrick J. O’Connor博士在一篇随刊述评中指出，该Meta分析结果强调临床医生和患者有必要权衡强化血糖控制方案的潜在获益和风险(如低血糖和死亡风险可能增加)，以及临床上重视其他方面(如降压、血脂控制和戒烟)治疗所可能带来的更大益处(Arch. Intern. Med. 2012:172:170-1)。

而在另一篇随刊述评中，麻省总医院糖尿病中心及综合临床研究中心主任David M. Nathan博士指出，该Meta分析所纳入的多数研究持续时间过短，以致无法断定强化血糖控制对肾病的影响。尽管实施强化治疗存在困难且会带来一定负担，但所有初步数据均表明长期强化治疗对患者有益(Arch. Intern. Med. 2012:172:769-70)。

一位研究者声明是United Healthcare公司的科学咨询委员会主席。其他人均声明无经济利益冲突。


Intensive glucose control had no apparent impact on renal outcomes in type 2 diabetes patients compared to conventional glucose control, according to meta-analysis findings published online in the May 28 Archives of Internal Medicine.

The American Diabetes Association and other expert panels recommend intensive control – defined as a target hemoglobin A1c of less than 7% – to help prevent renal disease and other microvascular complications in type 2 diabetes patients, but the impact of intensive control on clinical renal end points remains unclear, said Dr. Steven G. Coca, of Yale University, New Haven, Connecticut, and colleagues.
The investigators reviewed data from seven trials involving 28,065 adults with type 2 diabetes. Patient follow-up ranged from 2 to 15 years.

Compared with conventional control, intensive glucose control was associated with a reduced risk of microalbuminuria (risk ratio, 0.86) and macroalbuminuria (RR, 0.74).

However, there was no association with a reduced risk of several renal end points, including no doubling of the serum creatinine level (1.06), end-stage renal disease (0.69), or death from renal disease (0.99).
The mean serum creatinine levels at baseline ranged from 0.9 mg/dL to 1.0 mg/dL, and the mean duration of type 2 diabetes ranged from 7 to 12 years.

An additional meta-regression analysis supported the overall findings. In each study, differences in HbA1c between intensive and conventional control were associated with reduced risk of microalbuminuria and macroalbuminuria, but not with improved renal outcomes.

The results were limited by substantially incomplete outcomes data in several studies, the researchers noted. Many factors may contribute to the failure of tight glycemic control to improve renal outcomes. Possible factors include starting intensive glycemic control too late, failing to maintain intensive control long enough, failing to lower HbA1c levels to normal, and reaching an HbA1c level beyond which there is no additional benefit to the patient. Some of the studies also may have been underpowered to detect a significant difference in renal outcomes.

Despite these limitations, however, the researchers concluded that the current evidence fails to support tight control. “There is little compelling reason to initiate intensive glycemic control in midstage of the disease with the aim of preventing renal failure,” they wrote.

Most of the trials included in the meta-analysis were too short to draw conclusions about the impact of intensive glucose control on renal disease, according to Dr. David M. Nathan, director of the General Clinical Research Center and of the Diabetes Center at Massachusetts General Hospital in Boston.
“Although implementing intensive therapy is difficult and imposes burden and expense, all of the primary data continue to support its long-term benefit,” he said in an editorial that accompanied the study (Arch. Intern. Med. 2012:172:769-70).

However, Dr. Karen L. Margolis and Dr. Patrick J. O’Connor of HealthPartners Research Foundation, Minneapolis, said that the study findings underscore the need for clinicians and patients to weigh the risks and benefits of the treatment regimens needed for intensive glucose control.

“We conclude that for many patients with T2DM, the potential benefits of multidrug intensive glucose control regimens, which are only marginally supported by current evidence, must be weighed against the potential risks of such therapy (including hypoglycemia and possible increased mortality risks) as well as the potentially larger benefits of focusing clinical attention on other domains, such as blood pressure lowering, lipid control, and smoking cessation,” they wrote in another editorial (Arch. Intern. Med. 2012:172:170-1).

Dr. Coca and the editorialists reported having no financial conflicts of interest. Study coauthor Dr. Harlan M. Krumholz is the chair of a scientific advisory board for United Healthcare.