Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients

摘要： 应激性高血糖（SH），定义为血糖（BG）>140 mg/dL，据报道，在30%以上的一般人群中， 无糖尿病（DM）既往史的手术患者， 与维持正常血糖的患者或有已知病史的患者相比， DM.据推测，与应激相关的反调节激素和炎症/氧化性激素的增加可能与应激相关。 易感个体的应激标记物可能导致显著的胰岛素抵抗和SH的发展。 然而，没有前瞻性研究确定SH的临床预测因子和潜在机制， 手术病人该提案的目标是：1）检查临床、代谢和炎症/氧化 接受普通和血管手术的高风险心功能障碍患者的应力分布，a） 胰岛素分泌和敏感性的动态评估，和B）炎症/氧化应激水平 生物标志物[脂联素、皮质醇、游离脂肪酸（FFA）、C反应蛋白（hsCRP）、肿瘤坏死因子- α（TNF-α），硫代巴比妥酸反应物质（TBARS）]; 2）确定时间，持续时间和 通过动态血糖监测（CGM）和床旁血糖检测确定的SH严重程度及其相关性 与生物标志物的变化; 3）探讨SH与围手术期并发症的复合关系 （伤口感染、呼吸衰竭、肺炎、急性肾损伤和主要不良心脏事件）; 4） 进行一项随机对照的初步研究，以确定是否单剂量给药的dulcantine，一次 低血糖风险低的一周抗糖尿病药物，可改善手术患者的血糖控制 有潜在的精神障碍（前驱糖尿病和新诊断的糖尿病），具有发生SH的高风险。的 与SH密切相关的临床、代谢和炎症信息将被用于开发一个 风险分层模型，用于识别术后SH高风险的手术患者。 除了阐明SH的风险因素和基本机制外，这一建议还将加强多方面的 多方面的研究培训和职业发展计划，使PI成为一个独立的 临床研究者PI将继续与经验丰富的指导和咨询团队一起工作 具有住院糖尿病管理、医院临床试验、糖尿病技术和 生物统计学上述培训得到了机构承诺的支持， 跨学科研究合作和推进PI的学术研究事业。

Abstract: Stress hyperglycemia (SH), defined as a blood glucose (BG) >140 mg/dL, is reported in over 30% of general surgery patients without a prior history of diabetes mellitus (DM) and is associated with an increased risk of complications and mortality compared to patients maintaining normoglycemia or those with a known history of DM. It is hypothesized that stress-related increases in counter-regulatory hormones and inflammatory/oxidative stress markers in susceptible individuals may lead to significant insulin resistance and the development of SH. However, no prospective studies have determined clinical predictors and underlying mechanisms of SH in surgical patients. The goals of this proposal are to: 1) examine clinical, metabolic and inflammatory/oxidative stress profiles of patients at high risk for dysglycemia undergoing general and vascular surgery with, a) dynamic assessment of insulin secretion and sensitivity, and b) levels of inflammatory/oxidative stress biomarkers [adiponectin, cortisol, free fatty acids (FFA), C-reactive protein (hsCRP), tumor necrosis factor- alpha (TNF-α), thiobarbituric acid reactive substances (TBARS)]; 2) determine the timing, duration and severity of SH by continuous glucose monitoring (CGM) and point of care glucose testing and its association with biomarker changes; 3) explore the relationship of SH with a composite of perioperative complications (wound infection, respiratory failure, pneumonia, acute kidney injury and major adverse cardiac events); 4) conduct a randomized controlled pilot study to determine if single dose administration of dulaglutide, a once a week antidiabetic agent with low-risk of hypoglycemia, can improve glycemic control in surgical patients with underlying dysglycemia (prediabetes and newly-diagnosed diabetes) at high risk for developing SH. The clinical, metabolic, and inflammatory information most strongly associated with SH will be used to develop a risk stratification model for the identification of surgical patients at high-risk for SH postoperatively. In addition to delineating risk factors and underlying mechanisms of SH, this proposal will enhance the multi- faceted research training and career development plan necessary for the PI to become an independent clinical investigator. The PI will continue to work alongside an experienced mentorship and advisory team with expertise in inpatient diabetes management, clinical trials in hospital settings, diabetes technology and biostatistics. This aforementioned training is supported by an institutional commitment to establishing interdisciplinary research collaborations and advancing the PI’s career in academic research.