Determinants of Brain Natriuretic Peptide in Diabetes

2型糖尿病（T2DM）是心力衰竭（HF）的重要危险因素，在美国越来越普遍。流行病学证据表明，血压升高、糖化血红蛋白升高和肥胖增加是糖尿病患者心衰的危险因素。目前还没有一种简单的、临床上有用的方法来对糖尿病患者的未来心衰风险进行风险分层。这引起了人们对利用血液测试测量NT-proBNP作为糖尿病患者风险分层的一部分的兴趣。心肌细胞释放proBNP，其分裂为活性BNP和非活性NT-proBNP，在血液中更稳定。两者高度相关，可用于诊断急性心衰。NT-proBNP已被证明可以预测未来的心衰、其他心血管事件和死亡率。然而，小型研究表明，在糖尿病患者中，体重指数（BMI）和糖化血红蛋白的增加与BNP/NT-pro BNP水平的降低而不是升高有关。考虑到HbA1c或BMI与HF之间的关系，这些关联是违反直觉的。此外，没有明显心力衰竭的糖尿病患者NT-proBNP随时间变化的数据很少。了解T2DM患者HF危险因素与NT-proBNP之间的真正关系，才能有效预防HF。因此，我们建议对前瞻性（糖尿病健康行动）进行一项辅助研究，这是一项多中心随机试验，在2001- 2004年期间招募了5145名超重和肥胖的2型糖尿病成年人，以确定强化生活方式干预的长期效果，该干预旨在通过减少热量摄入和增加身体活动来实现和维持体重减轻，而不是对照条件，糖尿病支持和教育（DSE），对心血管死亡的综合发生率。非致死性心肌梗死和非致死性中风。一年后，干预对体重的影响为-8.3%，而DSE组为-0.4%。本研究建议在1500名无心血管疾病的Look AHEAD参与者（每组750人）中检测NT- proBNP，这些参与者从基线和一年内保存冷冻血液样本。这项研究将有助于更好地了解超重糖尿病成年人NT-proBNP的相关因素，并确定生活方式干预是否会降低NT-proBNP。这项研究提出可能有助于更好地识别心力衰竭高风险的糖尿病成年人，并采取针对性的预防措施。这一点很重要，因为心力衰竭在美国是一种常见的、致命的、昂贵的疾病。公共卫生相关性众所周知，血液中NT-proBNP水平可以预测谁会患上心脏病，包括心力衰竭，但在糖尿病患者中，NT-proBNP的决定因素尚不清楚。本项目旨在更好地了解NT-proBNP水平，并测试减肥干预是否会降低糖尿病患者血液中NT-proBNP的含量。这可能有助于更好地预防糖尿病患者的心力衰竭，这一点很重要，因为心力衰竭是糖尿病常见且致命的并发症。

DESCRIPTION (provided by applicant): Abstract Type 2 diabetes mellitus (T2DM) is a strong risk factor for heart failure (HF), and is increasingly prevalent in the US. Epidemiologic evidence suggests increased blood pressure, higher hemoglobin A1c and increased obesity are risk factors for HF among diabetics. Currently there is not a simple, clinically useful way to risk- stratify diabetic patients with respect to future HF risk. This has led to interest in utilizing a blood test measuring NT-proBNP as part of risk stratification in persons with diabetes. Cardiac myocytes release proBNP, which is cleaved into the active BNP and inactive NT-proBNP, which is more stable in blood. The two are highly correlated and are utilized in diagnosing acute HF. NT-proBNP has been shown to be predictive of future HF, other cardiovascular events, and mortality. However small studies have suggested that increased body mass index (BMI) and A1c is associated with lower, rather than higher BNP/NT-pro BNP levels, in diabetics. These associations are counterintuitive, given the suggested relationship between HbA1c or BMI and HF. Furthermore, there is little data regarding change in NT-proBNP over time in diabetics without overt heart failure. Understanding the true relationship between risk factors for HF and NT-proBNP in T2DM is required before it could be useful to target HF prevention. Thus we propose an ancillary study to Look AHEAD (Action for Health in Diabetes) a multicenter, randomized trial which enrolled 5,145 overweight and obese adults with T2DM during 2001-04, to determine the long-term effects of an intensive lifestyle intervention designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity versus a control condition, diabetes support and education (DSE), on the combined incidence of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. At one year, the effect of the intervention on weight was -8.3%, compared to -0.4% in the DSE group. This study proposes to test for NT- proBNP in 1500 Look AHEAD participants free of cardiovascular disease (750 in each arm) in stored frozen blood samples from baseline and one year. This study will lead to a better understanding of the correlates of NT-proBNP in overweight diabetic adults, and determine if a lifestyle intervention reduces NT-proBNP. The research proposed may lead to efforts to better identify diabetic adults at high risk for heart failure, and target prevention efforts. This is important, as heart failure is a common, deadly, and expensive illness in the U.S.PUBLIC HEALTH RELEVANCE It is known that blood levels of NT-proBNP can predict who will develop heart disease, including heart failure, but among diabetic persons, to determinants of NT-proBNP are not clear. This project aims to better understand NT-proBNP levels, and to test whether a weight loss intervention reduces the amount of NT- proBNP in the blood of diabetics. This may help better prevent heart failure in diabetics, which is important because heart failure is a common and deadly complication of diabetes.