Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies,Diabetologia

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Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies
Diabetologia ( IF 8.4 ) Pub Date : 2021-10-31 , DOI: 10.1007/s00125-021-05592-3
Sabrina Schlesinger _{1,

2} , Manuela Neuenschwander _{1,

2} , Janett Barbaresko ₁ , Alexander Lang ₁ , Haifa Maalmi _{2,

3} , Wolfgang Rathmann _{1,

2} , Michael Roden _{2,

3,

4} , Christian Herder _{2,

3,

4}

Affiliation

Aims/hypothesis

The term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA_1c levels are not yet high enough to be diagnosed as diabetes. Prediabetes may already be associated with an increased risk of chronic ‘diabetes-related’ complications. This umbrella review aimed to provide a systematic overview of the available evidence from meta-analyses of prospective observational studies on the associations between prediabetes and incident diabetes-related complications in adults and to evaluate their strength and certainty.

Methods

For this umbrella review, systematic reviews with meta-analyses reporting summary risk estimates for the associations between prediabetes (based on fasting or 2 h postload glucose or on HbA_1c) and incidence of diabetes-related complications, comorbidities and mortality risk were included. PubMed, Web of Science, the Cochrane Library and Epistemonikos were searched up to 17 June 2021. Summary risk estimates were recalculated using a random effects model. The certainty of evidence was evaluated by applying the GRADE tool. This study is registered with PROSPERO, CRD42020153227.

Results

Ninety-five meta-analyses from 16 publications were identified. In the general population, prediabetes was associated with a 6–101% increased risk for all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, heart failure, atrial fibrillation and chronic kidney disease, as well as total cancer, total liver cancer, hepatocellular carcinoma, breast cancer and all-cause dementia with moderate certainty of evidence. No associations between prediabetes and incident depressive symptoms and cognitive impairment were observed (with low or very low certainty of evidence). The association with all-cause mortality was stronger for prediabetes defined by impaired glucose tolerance than for prediabetes defined by HbA_1c.

Conclusions/interpretation

Prediabetes was positively associated with risk of all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, chronic kidney disease, cancer and dementia. Further high-quality studies, particularly on HbA_1c-defined prediabetes and other relevant health outcomes (e. g. neuropathy) are required to support the evidence.

Graphical abstract

中文翻译：

糖尿病前期和死亡风险、糖尿病相关并发症和合并症：前瞻性研究荟萃分析的总体回顾

目标/假设

糖尿病前期一词用于葡萄糖代谢受损的个体，其葡萄糖或 HbA _1c水平尚未高到足以被诊断为糖尿病。糖尿病前期可能已经与慢性“糖尿病相关”并发症的风险增加有关。这篇综述旨在系统地概述来自前瞻性观察研究的荟萃分析的可用证据，这些研究涉及成人糖尿病前期与糖尿病相关并发症之间的关联，并评估其强度和确定性。

方法

在这项综合性综述中，系统综述和荟萃分析报告了糖尿病前期（基于空腹或负荷后 2 小时血糖或 HbA _1c）与糖尿病相关并发症发生率、合并症和死亡风险之间关联的总结风险估计。PubMed、Web of Science、Cochrane Library 和 Epistemonikos 的检索时间截至 2021 年 6 月 17 日。使用随机效应模型重新计算了汇总风险估计。通过应用 GRADE 工具评估证据的确定性。本研究已在 PROSPERO 注册，CRD42020153227。

结果

确定了来自 16 篇出版物的 95 篇荟萃分析。在一般人群中，糖尿病前期与全因死亡率和心血管结局、冠心病、中风、心力衰竭、心房颤动和慢性肾病以及总癌症、总肝病的发生率增加 6-101% 相关癌症、肝细胞癌、乳腺癌和全因痴呆，证据质量中等。未观察到糖尿病前期与抑郁症状和认知障碍之间的关联（证据质量低或非常低）。由糖耐量受损定义的前驱糖尿病与由 HbA _1c定义的前驱糖尿病相比，与全因死亡率的相关性更强。