Glycemic control and variability in congestive heart failure exacerbation

描述（由申请人提供）：充血性心力衰竭（CHF）在美国造成了巨大的医疗、社会和经济负担，住院治疗占了大部分费用。超过40%的住院CHF患者患有糖尿病，并且已经发现在急性疾病期间治疗高血糖症可以改善其他疾病状态的发病率和死亡率。然而，充血性心力衰竭恶化和血糖控制改善之间的关系尚不清楚。研究报告急性（“应激”）高血糖而非慢性高血糖可预测CHF死亡率，提示急性血糖不稳定可能很重要。因此，研究者希望前瞻性地确定血糖变异性是否与CHF加重期间的结局相关。在体外试验中，与补充性葡萄糖升高相比，甘氨酸变异性与更严重的内皮毒性相关，在糖尿病患者中，它与氧化应激和缺血性EKG变化相关，与持续高血糖无关。糖化血红蛋白变异性也与ICU死亡率独立相关，但除此之外，尚未在任何住院患者人群中进行前瞻性研究。本研究的主要目的是确定接受持续静脉胰岛素治疗的CHF患者相对于生理性皮下胰岛素治疗方案是否改善了血糖变异性，并研究血糖变异性是否导致CHF患者既定预后变量的改善。具体而言，该研究将检查CHF恶化患者的心率变异性、炎症标志物、内皮功能、BNP、氧化应激、疾病严重程度和生活质量评分。该方案将在俄亥俄州州立大学Ross心脏医院收治的80例高血糖症和因收缩功能障碍（射血分数<35%）导致的失代偿性心力衰竭患者中进行。患者将被随机分配至2组之一：（1）静脉胰岛素治疗，目标血糖为150 mg/dL，（2）皮下胰岛素，含基础、餐时和补充成分。每小时检查所有患者的血糖。静脉注射胰岛素将持续72小时。结果将应用于更大的患者群体，以检查硬临床终点。公共卫生相关性：尽管心力衰竭的医疗保健取得了进展，但住院和死亡人数仍在上升，糖尿病患者的风险也在增加。目前的研究调查了心力衰竭恶化期间血糖（葡萄糖）的波动是否起作用。

DESCRIPTION (provided by applicant): Congestive heart failure (CHF) poses an enormous medical, societal and financial burden in the U.S, and hospitalization accounts for the majority of costs. Over 40% of hospitalized CHF patients have diabetes, and treatment of hyperglycemia during acute illness has been found to improve morbidity and mortality in other disease states. However, the relationship between congestive heart failure exacerbation and improved glycemic control is not known. Studies report that acute ("stress") hyperglycemia, but not chronic hyperglycemia predicts CHF mortality, suggesting that acute glycemic instability may be important. The investigators therefore wish to determine prospectively whether glycemic variability is related to outcomes during CHF exacerbation. Glycemic variability is associated with more profound endothelial toxicity than tonic glucose elevations in vitro, and in patients with diabetes, it is associated with oxidative stress and ischemic EKG changes, independent of sustained hyperglycemia. Glycemic variability has also been independently associated with ICU mortality, but otherwise, it has not been studied prospectively in any hospitalized patient population. The primary aims of this study are to determine whether CHF patients undergoing continuous intravenous insulin therapy have improved glycemic variability relative to a physiologic subcutaneous insulin regimen, and to investigate whether glycemic variability leads to improvement in established prognostic variables in patients with CHF. Specifically, the study will examine heart rate variability, markers of inflammation, endothelial function, BNP, oxidative stress, disease severity, and quality of life scores in patients with CHF exacerbation. This protocol will be conducted among 80 patients admitted to the Ohio State University Ross Heart Hospital with hyperglycemia and decompensated heart failure due to systolic dysfunction (ejection fraction <35%). Patients will be randomly assigned to one of 2 groups: (1) intravenous insulin therapy targeting a blood glucose of 150 mg/dL, (2) subcutaneous insulin with basal, prandial, and supplemental components. Glucose will be checked hourly in all patients. Intravenous insulin will be continued for 72 hours. The results will be applied to larger patient populations in order to examine hard clinical endpoints. PUBLIC HEALTH RELEVANCE: Despite advances in medical care for heart failure, hospitalizations and deaths are rising, and patients with diabetes are at increased risk. The current study investigates whether fluctuations in blood sugar (glucose) during deterioration of heart failure play a role.