The Effect of Sex Hormones on Cardiometabolic Outcomes in Men and Women with Diabetes: The Look AHEAD (Action for Health in Diabetes) Study

性激素对男性和女性糖尿病患者心脏代谢结果的影响：展望未来（糖尿病健康行动）研究

• 批准号: 10262947
• 负责人: Wendy Lynet Bennett
• 金额: $ 71.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10262947
• 关键词: Address; Age; Albumins; Biological; Blood Pressure; Body Composition; Body Weight decreased; Body mass index; Cardiovascular Diseases; Chronic Disease; Chronic Kidney Failure; Clinical; Control Groups; Coronary heart disease; Data; Diabetes Mellitus; Disadvantaged; Eating; Education; Estradiol; Etiology; Event; Female; General Population; Glycosylated hemoglobin A; Gonadal Steroid Hormones; Health; Hormonal Change; Individual; Life Style; Life Style Modification; Lipids; Longitudinal Studies; Measurement; Morbidity - disease rate; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Overweight; Participant; Physical activity; Prevalence; Preventive measure; Preventive treatment; Randomized Controlled Trials; Recommendation; Relative Risks; Research; Risk; Risk Factors; Role; Sex Differences; Sex Hormone-Binding Globulin; Stroke; Testing; Testosterone; Time; United States National Institutes of Health; Vascular Dementia; Weight; Woman; adjudicate; adverse outcome; cardiometabolic risk; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; clinically significant; comparison intervention; design; diabetes management; diet and exercise; follow-up; healthy lifestyle; improved; kidney vascular structure; lifestyle intervention; men; mortality; primary outcome; response; sex; treatment arm; waist circumference

Although women and men have about an equal prevalence of type 2 diabetes (DM), DM imposes a clinically significant excess relative risk of coronary heart disease (44% higher), stroke (27% higher) and vascular dementia (19% higher) in women compared to men. Understanding these sex differences could inform research to improve DM outcomes for both women and men. Postulated reasons for the “female disadvantage” include an adverse cardiometabolic profile (particularly greater obesity) and disparities in aggressiveness of CV preventive treatments (e.g. use of statins). In addition, differences in endogenous sex hormones, including estradiol (E2), testosterone (T) and sex hormone binding globulin (SHBG), may contribute to the excess risk for women conferred by DM. Although lifestyle changes (diet, exercise and weight loss) are the cornerstone of diabetes management, it is not known if weight loss and healthier lifestyle can modulate the trajectory of sex hormones over time, and the role of these hormonal changes on cardiometabolic risk factors. The Action for Health In Diabetes (Look AHEAD) Study was a randomized controlled trial among 5,145 overweight individuals with obesity and type 2 diabetes designed to evaluate the effect of an Intensive Lifestyle Intervention (ILI) compared to a control group on incident CVD events. A major strength of Look AHEAD is its capacity to address questions of causation, because study participants were followed over 8 years (~3000 with longitudinal biospecimens for sex hormone measurements), with significant and well-characterized alterations in weight and with adjudicated clinical outcomes. In this proposal, we will first analyze the stored biospecimens for sex hormones (E2, T), SHBG and albumin. We will then 1) Test whether the ILI improves endogenous sex hormones over time and whether the effect of ILI is moderated by sex; 2) Evaluate the longitudinal associations between endogenous sex hormones and cardiometabolic risk factors (HbA1c, lipid levels, body mass index and weight, waist circumference, body composition, blood pressure) (primary outcomes); 3) Test the effect of the time-trajectory of endogenous sex hormones on improving cardio-metabolic risk factors and long term DM outcomes (i.e. CVD, stroke, chronic kidney disease and vascular dementia) over 8 years of followup, and whether differences exist by sex. Our overall hypothesis is that ILI improves the sex hormone profile, and that an unfavorable sex hormone profile, i.e. high free T in women and low free T in men, is associated with an adverse cardiometabolic risk profile. Ultimately, understanding the biological role of sex hormones in DM could target treatments, particularly lifestyle modification, and inform the prevention of CVD and other DM complications, to reduce DM-related morbidity and mortality for both women and men.

尽管男女的2型糖尿病（DM）的患病率大约相等，但DM在临床上不可能 显着超过冠心病的相对风险（高44％），中风（高27％）和血管 与男性相比，女性的痴呆症（增长19％）。了解这些性别差异可以告知 研究以改善男女的DM结果。假定“女性灾难”的原因 包括不良心脏代谢轮廓（尤其是更大的对象性）和侵略性的差异 简历预防治疗（例如使用他汀类药物）。此外，内源性激素的差异，包括 雌二醇（E2），睾丸激素（T）和性激素结合球蛋白（SHBG）可能有助于多余的风险 对于由DM授予的女性。尽管生活方式改变（饮食，运动和减肥）是 糖尿病管理，尚不清楚体重减轻和健康生活方式是否可以调节性轨迹 随着时间的流逝，骑马的角色以及这些骑士变化对心脏代谢危险因素的作用。动作 糖尿病的健康（前面）研究是5,145个超重个体中的一项随机对照试验 肥胖和2型糖尿病旨在评估密集生活方式干预的影响（ILI） 与事件CVD事件的对照组相比。展望的主要优势是它的能力 解决因果关系的问题，因为研究参与者在8年中受到了研究（约3000年） 性激素测量的纵向生物测量），具有重大和良好的变化 体重和调整后的临床结果。在此提案中，我们将首先分析存储的生物测量 用于性激素（E2，T），SHBG和白蛋白。然后我们将1）测试ILI是否改善内源性 随着时间的流逝，骑马以及ILI的影响是否受到性的调节； 2）评估纵向 内源性激素与心脏代谢危险因素之间的关联（HBA1C，脂质水平，身体 质量指数和体重，腰围，身体成分，血压）（主要结果）； 3）测试 内源性性恐怖仪的时间对象对改善心脏代谢风险因素和 长期DM结果（即CVD，中风，慢性肾脏疾病和血管性痴呆）在8年内 跟进以及是否存在性别存在差异。我们的总体假设是ILI改善了性爱 个人资料，以及不利的性激素概况，即女性的高自由t和男性低的自由t是 与不良心脏代谢风险概况有关。最终，了解性的生物学作用 DM中的骑马可以针对治疗，尤其是生活方式修改，并告知预防CVD 以及其他DM并发症，以降低男女与DM相关的发病率和死亡率。