Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis,The Lancet

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Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis
The Lancet ( IF 98.4 ) Pub Date : 2021-11-11 , DOI: 10.1016/s0140-6736(21)01920-6
Milad Nazarzadeh ₁ , Zeinab Bidel ₁ , Dexter Canoy ₂ , Emma Copland ₁ , Malgorzata Wamil ₃ , Jeannette Majert ₁ , Karl Smith Byrne ₄ , Johan Sundström ₅ , Koon Teo ₆ , Barry R Davis ₇ , John Chalmers ₈ , Carl J Pepine ₉ , Abbas Dehghan ₁₀ , Derrick A Bennett ₁₁ , George Davey Smith ₁₂ , Kazem Rahimi ₂ ,

Affiliation

Deep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK.
Deep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, Medical Science Division, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Deep Medicine, Oxford Martin School, University of Oxford, Oxford, UK.
International Agency for Research on Cancer/WHO, Genomic Epidemiology Branch, Lyon, France.
Clinical Epidemiology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
The University of Texas School of Public Health, Houston, TX, USA.
The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Department of Medicine, University of Florida, Gainesville, FL, USA.
Department of Biostatistics and Epidemiology, School of Public Health, Imperial College London, London, UK.
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Background

Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.

Methods

We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists’ Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.

Findings

145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84–0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76–0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76–0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27–1·72]) and thiazide diuretics (RR 1·20 [1·07–1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92–1·13]).

Interpretation

Blood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual's clinical risk of diabetes.

Funding

British Heart Foundation, National Institute for Health Research, and Oxford Martin School.

中文翻译：

血压降低和新发 2 型糖尿病的风险：个体参与者数据荟萃分析

背景

降低血压是预防糖尿病微血管和大血管并发症的既定策略，但其在预防糖尿病本身中的作用尚不清楚。我们的目的是使用来自主要随机对照试验的个体参与者数据来研究这个问题。

方法

我们进行了一项单阶段个体参与者数据荟萃分析，其中汇总数据来研究降低血压本身对新发 2 型糖尿病风险的影响。使用个体参与者数据网络荟萃分析来研究五种主要抗高血压药物对新发 2 型糖尿病风险的差异影响。总体而言，1973 年至 2008 年间进行的 22 项研究的数据由降血压治疗试验者合作组织（英国牛津大学）获得。我们纳入了所有一级和二级预防试验，这些试验使用特定类别或类别的抗高血压药物与安慰剂或其他类别的降压药物进行比较，并且在每个随机分配的组中进行了至少 1000 人年的随访。基线时已知患有糖尿病的参与者以及在患有糖尿病的患者中进行的试验被排除在外。对于一阶段个体参与者数据荟萃分析，我们使用分层 Cox 比例风险模型，对于个体参与者数据网络荟萃分析，我们使用逻辑回归模型来计算药物类别比较的相对风险 (RR)。

发现

来自 19 项随机对照试验的 145 939 名参与者（88 500 [60·6%] 男性和 57 429 [39·4%] 女性）被纳入一阶段个体参与者数据荟萃分析。 22 项试验被纳入个体参与者数据网络荟萃分析中。经过中位随访 4·5 年 (IQR 2·0)，9883 名参与者被诊断患有新发 2 型糖尿病。在所有试验中，收缩压降低 5 mm Hg 可使 2 型糖尿病风险降低 11%（风险比 0·89 [95% CI 0·84–0·95]）。对五类主要抗高血压药物的作用的调查表明，与安慰剂相比，血管紧张素转换酶抑制剂（RR 0·84 [95% 0·76–0·93]）和血管紧张素 II 受体阻滞剂（RR 0·84） [0·76–0·92]）降低新发2型糖尿病的风险；然而，使用β受体阻滞剂（RR 1·48 [1·27–1·72]）和噻嗪类利尿剂（RR 1·20 [1·07–1·35]）增加了这种风险，并且没有发现实质性影响用于钙通道阻滞剂（RR 1·02 [0·92–1·13]）。

解释

降低血压是预防新发2型糖尿病的有效策略。然而，已建立的药物干预措施对糖尿病具有定性和定量的不同影响，这可能是由于它们不同的脱靶效应，其中血管紧张素转换酶抑制剂和血管紧张素 II 受体阻滞剂具有最有利的结果。这一证据支持了选定类别的抗高血压药物用于预防糖尿病的适应症，这可以根据个人的糖尿病临床风险进一步细化药物选择。

资金

英国心脏基金会、国家健康研究所和牛津马丁学院。

更新日期：2021-11-12

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