Callaghan Brian C, Little Ann A, Feldman Eva L, Hughes Richard A C
Department of Neurology, University ofMichigan, Ann Arbor,Michigan, USA.
Cochrane Database Syst Rev. 2012 Jun 13;2012(6):CD007543. doi: 10.1002/14651858.CD007543.pub2.
There are two types of diabetes. Type 1 diabetes affects younger people and needs treatment with insulin injections. Type 2 diabetes affects older people and can usually be treated by diet and oral drugs. Diabetic neuropathy affects 10% of patients with diabetes mellitus at diagnosis and 40% to 50% after 10 years. Enhanced glucose control is the best studied intervention for the prevention of this disabling condition but there have been no systematic reviews of the evidence.
To examine the evidence for enhanced glucose control in the prevention of distal symmetric polyneuropathy in people with type 1 and type 2 diabetes.
We searched the Cochrane Neuromuscular Disease Group Specialized Register (30 January 2012), CENTRAL (2012, Issue 1), MEDLINE (1966 to January 2012) and EMBASE (1980 to January 2012) for randomized controlled trials of enhanced glucose control in diabetes mellitus.
We included all randomized, controlled studies investigating enhanced glycemic control that reported neuropathy outcomes after at least one year of intervention. Our primary outcome measure was annual development of clinical neuropathy defined by a clinical scale. Secondary outcomes included motor nerve conduction velocity and quantitative vibration testing.
Two authors independently reviewed all titles and abstracts identified by the database searches for inclusion. Two authors abstracted data from all included studies with a standardized form. A third author mediated conflicts. We analyzed the presence of clinical neuropathy with annualized risk differences (RDs), and conduction velocity and quantitative velocity measurements with mean differences per year.
This review identified 17 randomized studies that addressed whether enhanced glucose control prevents the development of neuropathy. Seven of these studies were conducted in people with type 1 diabetes, eight in type 2 diabetes, and two in both types. A meta-analysis of the two studies that reported the primary outcome (incidence of clinical neuropathy) with a total of 1228 participants with type 1 diabetes revealed a significantly reduced risk of developing clinical neuropathy in those with enhanced glucose control, an annualized RD of -1.84% (95% confidence interval (CI) -1.11 to -2.56). In a similar analysis of four studies that reported the primary outcome, involving 6669 participants with type 2 diabetes, the annualized RD of developing clinical neuropathy was -0.58% (95% CI 0.01 to -1.17). Most secondary outcomes were significantly in favor of intensive treatment in both populations. However, both types of diabetic participants also had a significant increase in severe adverse events including hypoglycemic events.
AUTHORS' CONCLUSIONS: According to high-quality evidence, enhanced glucose control significantly prevents the development of clinical neuropathy and reduces nerve conduction and vibration threshold abnormalities in type 1 diabetes mellitus. In type 2 diabetes mellitus, enhanced glucose control reduces the incidence of clinical neuropathy, although this was not formally statistically significant (P = 0.06). However, enhanced glucose control does significantly reduce nerve conduction and vibration threshold abnormalities. Importantly, enhanced glucose control significantly increases the risk of severe hypoglycemic episodes, which needs to be taken into account when evaluating its risk/benefit ratio.
糖尿病有两种类型。1型糖尿病多影响年轻人，需要注射胰岛素进行治疗。2型糖尿病多影响老年人，通常可通过饮食和口服药物治疗。糖尿病神经病变在糖尿病患者确诊时影响10%，10年后影响40%至50%。强化血糖控制是预防这种致残性疾病研究得最多的干预措施，但尚未对相关证据进行系统评价。
研究强化血糖控制在预防1型和2型糖尿病患者远端对称性多发性神经病变方面的证据。
我们检索了Cochrane神经肌肉疾病组专业注册库（2012年1月30日）、Cochrane系统评价数据库（2012年第1期）、医学期刊数据库（1966年至2012年1月）和荷兰医学文摘数据库（1980年至2012年1月），以查找关于糖尿病强化血糖控制的随机对照试验。
我们纳入了所有调查强化血糖控制且报告了至少一年干预后神经病变结局的随机对照研究。我们的主要结局指标是根据临床量表定义的临床神经病变的年度发生率。次要结局包括运动神经传导速度和定量振动测试。
两名作者独立审查数据库检索出的所有标题和摘要以确定是否纳入。两名作者使用标准化表格从所有纳入研究中提取数据。第三名作者调解分歧。我们用年度风险差值分析临床神经病变的存在情况，用每年的平均差值分析传导速度和定量速度测量结果。
本综述确定了17项随机研究，这些研究探讨了强化血糖控制是否可预防神经病变的发生。其中7项研究针对1型糖尿病患者，8项针对2型糖尿病患者，2项针对两种类型的患者。对两项报告了主要结局（临床神经病变发生率）的研究进行的荟萃分析，共涉及1228例1型糖尿病患者，结果显示强化血糖控制组发生临床神经病变的风险显著降低，年度风险差值为-1.84%（95%置信区间-1.11至-2.56）。对4项报告了主要结局的研究进行的类似分析，涉及6669例2型糖尿病患者，发生临床神经病变的年度风险差值为-0.58%（95%置信区间0.01至-1.17）。在这两类人群中，大多数次要结局均显著支持强化治疗。然而，两类糖尿病患者严重不良事件（包括低血糖事件）的发生率也显著增加。
根据高质量证据，强化血糖控制可显著预防1型糖尿病患者临床神经病变的发生，并减少神经传导和振动阈值异常。在2型糖尿病患者中，强化血糖控制可降低临床神经病变的发生率，尽管这在统计学上未达到正式显著性水平（P = 0.06）。然而，强化血糖控制确实可显著降低神经传导和振动阈值异常。重要的是，强化血糖控制会显著增加严重低血糖事件的风险，在评估其风险/效益比时需要考虑这一点。
