Type 2 diabetes and cause-specific mortality in Mexico City: a Mendelian randomisation analysis

IF 7 Q1 HEALTH CARE SCIENCES & SERVICES

Lancet Regional Health-Americas Pub Date : 2025-04-06 DOI:10.1016/j.lana.2025.101082

Fiona Bragg , Pablo Kuri-Morales , Eirini Trichia , Jason M. Torres , Paulina Baca , Adrián Garcilazo-Ávila , Carlos González-Carballo , Raul Ramirez-Reyes , Fernando Rivas , Diego Aguilar-Ramirez , Louisa Gnatiuc-Friedrichs , William G. Herrington , Michael Hill , Tianshu Liu , Alejandra Vergara , Rachel Wade , Rory Collins , Richard Peto , Jaime Berumen , Jesus Alegre-Díaz , Roberto Tapia-Conyer

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Abstract

Background

Observational epidemiological studies in Mexico have shown high mortality risks associated with type 2 diabetes (T2D). However, it is unclear whether these relationships are wholly causal. We aimed to assess the association of genetically-predicted T2D liability with risk of death in Mexico.

Methods

Between 1998 and 2004, 150,000 men and women were recruited from Mexico City and followed-up until September 2022 for cause-specific mortality. Mendelian randomisation analyses, using a genetic risk score (GRS) comprising 1055 established T2D-associated risk variants, estimated associations with risk of all-cause and cause-specific mortality at ages 35–74.

Findings

Among 121,433 included participants with a mean (standard deviation) age of 51 (11), 68% (n = 82,249) were women and 18% (n = 21,371) had T2D. The GRS explained 6.3% of T2D liability and was not associated with major potential confounders of the T2D-mortality relationship. During a median (interquartile range) of 20.2 (19.4–21.4) years’ follow-up, 12,293 participants died. Genetically-predicted T2D liability was associated with a death rate ratio (RR) of 1.29 (95% confidence interval [CI] 1.23–1.36) per trebling in genetically-predicted odds of T2D. There were particularly strong associations with death from renal disease (n = 1696; RR 2.29 [95% CI 1.99–2.64]) and acute diabetic crises (n = 509; RR 2.27 [1.75–2.93]) and weaker, but still strong, associations with death from vascular disease (n = 3226; RR 1.31 [1.19–1.46]) and infection (n = 2437; RR 1.21 [1.07–1.36]). Genetically-predicted T2D liability was not clearly associated with death from cancer (n = 2016; RR 1.00 [95% CI 0.88–1.14]) or cirrhosis (n = 895; RR 0.90 [0.74–1.10]).

Interpretation

T2D is causally associated with death from vascular, renal and infectious diseases. Its prevention and effective management could substantially reduce premature deaths in Mexico, where T2D is common.

Funding

Wellcome Trust, the Mexican Health Ministry, the National Council for Science and Technology (CONACyT) for Mexico, Cancer Research UK, British Heart Foundation, Kidney Research UK, UK Medical Research Council, AstraZeneca, Regeneron.

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背景墨西哥的流行病学观察研究显示，2 型糖尿病（T2D）具有很高的致死风险。然而，这些关系是否完全是因果关系尚不清楚。我们的目的是评估基因预测的 T2D 责任与墨西哥死亡风险之间的关联。方法在 1998 年至 2004 年间，我们从墨西哥城招募了 15 万名男性和女性，并对其特定原因死亡率进行了跟踪调查，直至 2022 年 9 月。研究结果在121,433名平均（标准差）年龄为51（11）岁的参与者中，68%（n = 82,249）为女性，18%（n = 21,371）患有T2D。GRS解释了6.3%的T2D责任，与T2D-死亡率关系的主要潜在混杂因素无关。在20.2（19.4-21.4）年的中位数（四分位数间距）随访期间，有12293名参与者死亡。基因预测的 T2D 责任与死亡率比 (RR) 有关，基因预测的 T2D 发生几率每增加三倍，死亡率比 (RR) 为 1.29（95% 置信区间 [CI] 1.23-1.36）。与肾脏疾病（n = 1696；RR 2.29 [95% CI 1.99-2.64]）和糖尿病急性危象（n = 509；RR 2.27 [1.75-2.93]）导致的死亡关系尤为密切，与血管疾病（n = 3226；RR 1.31 [1.19-1.46]）和感染（n = 2437；RR 1.21 [1.07-1.36]）导致的死亡关系较弱，但仍然密切。基因预测的 T2D 与癌症（n = 2016；RR 1.00 [95% CI 0.88-1.14]）或肝硬化（n = 895；RR 0.90 [0.74-1.10]）导致的死亡无明显关联。在T2D常见的墨西哥，预防和有效管理T2D可以大大减少过早死亡。

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来源期刊

Lancet Regional Health-Americas Multiple-

CiteScore

8.00

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0.00%

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期刊介绍： The Lancet Regional Health – Americas, an open-access journal, contributes to The Lancet's global initiative by focusing on health-care quality and access in the Americas. It aims to advance clinical practice and health policy in the region, promoting better health outcomes. The journal publishes high-quality original research advocating change or shedding light on clinical practice and health policy. It welcomes submissions on various regional health topics, including infectious diseases, non-communicable diseases, child and adolescent health, maternal and reproductive health, emergency care, health policy, and health equity.