Genetic Evidence Strongly Supports Managing Weight and Blood Pressure in Addition to Glycemic Control in Preventing Vascular Complications in People With Type 2 Diabetes.

IF 14.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Care Pub Date : 2023-10-01 DOI:10.2337/dc23-0855
Altayeb Ahmed, Hasnat Amin, Fotios Drenos, Naveed Sattar, Hanieh Yaghootkar
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Abstract

Objective: To investigate the causal association of type 2 diabetes and its components with risk of vascular complications independent of shared risk factors obesity and hypertension and to identify the main driver of this risk.

Research design and methods: We conducted Mendelian randomization (MR) using independent genetic variants previously associated with type 2 diabetes, fasting glucose, HbA1c, fasting insulin, BMI, and systolic blood pressure as instrumental variables. We obtained summary-level data for 18 vascular diseases (15 for type 2 diabetes) from FinnGen and publicly available genome-wide association studies as our outcomes. We conducted univariable and multivariable MR, in addition to sensitivity tests to detect and minimize pleiotropic effects.

Results: Univariable MR analysis showed that type 2 diabetes was associated with 9 of 15 outcomes; BMI and systolic blood pressure were associated with 13 and 15 of 18 vascular outcomes, respectively; and fasting insulin was associated with 4 and fasting glucose with 2. No robust association was found for HbA1c instruments. With adjustment for correlated traits in the multivariable test, BMI and systolic blood pressure, consistent causal effects were maintained, while five associations with type 2 diabetes (chronic kidney disease, ischemic heart disease, heart failure, subarachnoid hemorrhage, and intracerebral hemorrhage) were attenuated to null.

Conclusions: Our findings add strong evidence to support the importance of BMI and systolic blood pressure in the development of vascular complications in people with type 2 diabetes. Such findings strongly support the need for better weight and blood pressure management in type 2 diabetes, independent of glucose lowering, to limit important complications.

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遗传证据有力地支持在控制血糖的同时控制体重和血压,以预防2型糖尿病患者的血管并发症。
目的:研究2型糖尿病及其成分与血管并发症风险的因果关系,不依赖于共同的风险因素肥胖和高血压,并确定这种风险的主要驱动因素。研究设计和方法:我们使用先前与2型糖尿病、空腹血糖、HbA1c、空腹胰岛素、BMI和收缩压相关的独立遗传变异作为工具变量进行了孟德尔随机化(MR)。我们从FinnGen获得了18种血管疾病(15种为2型糖尿病)的汇总数据,并将公开的全基因组关联研究作为我们的结果。除了灵敏度测试外,我们还进行了单变量和多变量MR,以检测并最大限度地减少多效性影响。结果:单变量MR分析显示,2型糖尿病与15种结果中的9种相关;BMI和收缩压分别与18种血管结果中的13种和15种相关;空腹胰岛素与4相关,空腹血糖与2相关。HbA1c检测仪之间没有发现强有力的相关性。通过调整多变量测试中的相关特征,BMI和收缩压,保持了一致的因果效应,而与2型糖尿病的五种关联(慢性肾脏疾病、缺血性心脏病、心力衰竭、蛛网膜下腔出血和脑出血)被减弱为零。结论:我们的研究结果为支持BMI和收缩压在2型糖尿病患者血管并发症发生中的重要性提供了有力的证据。这些发现有力地支持了对2型糖尿病进行更好的体重和血压管理的必要性,而不依赖于血糖降低,以限制重要的并发症。
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来源期刊
Diabetes Care
Diabetes Care 医学-内分泌学与代谢
CiteScore
27.80
自引率
4.90%
发文量
449
审稿时长
1 months
期刊介绍: The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes. Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.
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