Wolfson Diabetes and Endocrine Clinic, Institute of Metabolic Sciences, Addenbrooke's Hospital, Cambridge University Foundation Hospital Trust, Box 281, Hills Road, Cambridge CB2 2QQ, UK.
Diabetologia. 2010 May;53(5):840-9. doi: 10.1007/s00125-009-1638-7. Epub 2010 Feb 3.
AIMS/HYPOTHESIS: Diabetes increases the risk of lower extremity amputation (LEA). Although epidemiological studies report positive associations between glycaemia and LEA, the magnitude of the risk is not adequately quantified and clinical trials to date have not provided conclusive evidence about glucose lowering and LEA risk. We synthesised the available prospective epidemiological data on the association between glycaemia measured by HbA(1c) and the risk of LEA in individuals with diabetes.
We searched electronic databases and reference lists of relevant articles. We considered prospective epidemiological studies that had measured HbA(1c) level and assessed LEA as an outcome among diabetic individuals without acute foot ulcerations or previous history of amputation. Of 2,548 citations identified, we included 14 studies comprising 94,640 participants and 1,227 LEA cases. We abstracted data using standardised forms and obtained data from investigators when required. Data included characteristics of study populations, HbA(1c) assay methods, outcome and covariates. Study-specific relative risk estimates were pooled using random-effects model meta-analysis; heterogeneity was explored with meta-regression analyses.
The overall RR for LEA was 1.26 (95% CI 1.16-1.36) for each percentage point increase in HbA(1c). There was considerable heterogeneity across studies (I (2) 76%, 67-86%; p < 0.001), which was not accounted for by recorded study characteristics. The estimated RR was 1.44 (95% CI 1.25-1.65) for type 2 diabetes and 1.18 (95% CI 1.02-1.38) for type 1 diabetes; however, the difference was not statistically significant (p = 0.09). We found no strong evidence for publication bias.
CONCLUSIONS/INTERPRETATION: There is a substantial increase in risk of LEA associated with glycaemia in individuals with diabetes. In the absence of conclusive evidence from trials, this paper provides further epidemiological support for glucose-lowering as a strategy to reduce amputation in a population without acute foot ulceration or former amputation; it also provides disease modellers with estimates to assess the overall burden of hyperglycaemia.
目的/假设:糖尿病会增加下肢截肢(LEA)的风险。尽管流行病学研究报告了血糖与 LEA 之间存在正相关关系,但风险的幅度尚未得到充分量化,迄今为止的临床试验并未提供关于降低血糖和 LEA 风险的确凿证据。我们综合了现有的关于 HbA(1c) 测量的血糖与糖尿病患者 LEA 风险之间关联的前瞻性流行病学数据。
我们搜索了电子数据库和相关文章的参考文献列表。我们考虑了前瞻性的流行病学研究,这些研究测量了 HbA(1c) 水平,并评估了糖尿病患者中没有急性足部溃疡或既往截肢史的 LEA 作为结局。在 2548 条引文识别出的,我们纳入了 14 项研究,共 94640 名参与者和 1227 例 LEA 病例。我们使用标准化表格提取数据,并在需要时从研究人员处获得数据。数据包括研究人群的特征、HbA(1c) 检测方法、结局和协变量。使用随机效应模型荟萃分析汇总研究特异性相对风险估计值;通过荟萃回归分析探索异质性。
HbA(1c) 每增加 1%,LEA 的总体 RR 为 1.26(95%CI 1.16-1.36)。研究之间存在很大的异质性(I(2)76%,67-86%;p < 0.001),这不能用记录的研究特征来解释。RR 估计值为 2 型糖尿病 1.44(95%CI 1.25-1.65)和 1 型糖尿病 1.18(95%CI 1.02-1.38);然而,差异无统计学意义(p = 0.09)。我们没有发现发表偏倚的有力证据。
结论/解释:在没有急性足部溃疡或既往截肢的人群中,血糖与 LEA 风险之间存在显著的相关性。在临床试验没有确凿证据的情况下,本文为降低血糖作为降低无急性足部溃疡或既往截肢人群截肢风险的策略提供了进一步的流行病学支持;它还为疾病建模者提供了评估高血糖总体负担的估计值。