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.

尽管男性和男性大约是2型糖尿病（DM）的平等预期，但DM在临床上施加了 冠心病（增长44％），中风（高27％）和Vascalar的显着过多相对风险 与男性相比 改善男性和男性的DM结果的研究。 包括不良心脏多代表概况（尤其是更大的观察率）和侵略性的差异 简历预防治疗（例如使用统计数据）。 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。 糖尿病管理，如果体重减轻和健康的生活方式可以调节性别的性别 激素随着时间的流逝以及激素变化对心脏代谢风险因素的作用 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 肥胖症和2型糖尿病旨在评估评估的生活方式生活方式干预（ILI） 与事件CVD事件的对照组相比。 解决因果关系的问题，因为研究参与者在8年以上进行了研究（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 在重量和裁决的临床结果中。 对于性激素（E2，T），SHBG和白蛋白。 随着时间的推移，激素以及ILI的影响是否由性别调节； 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）； 内源性性激素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，以及性别是否存在性差异。 概况，不利的性激素轮廓，即女性的高自由t和男性低的自由t 与不利的心脏代谢风险概况相关。 DM中的激素可以针对治疗，尤其是生活方式修改，并告知 和其他DM并发症，以降低男性和男性的DM相关发病率和死亡率。