Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients

摘要： 应激性高血糖(SH)，定义为血糖(BG)和血糖(GT；140 mg/dL)，据报道在超过30%的一般情况下 无糖尿病(DM)病史的手术患者，并与糖尿病风险增加相关 并发症和死亡率与维持正常血糖的患者或有已知病史的患者相比 DM。假设应激相关的逆调节激素和炎症/氧化增加 易感个体的应激标志物可能导致显著的胰岛素抵抗和SH的发生。 然而，尚无前瞻性研究确定重型肝炎的临床预测因素和潜在机制。 外科病人。这项建议的目标是：1)检查临床、代谢和炎症/氧化 接受普通和血管手术的血糖异常高危患者的压力分布，a) 动态评估胰岛素分泌和敏感性，以及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(肿瘤坏死因子-α)、硫代巴比妥酸活性物质[2)确定时间、持续时间和 连续血糖监测(CGM)和临床点血糖试验对SH的严重程度及其相关性 3)探讨重型肝炎与围手术期并发症的关系 (伤口感染、呼吸衰竭、肺炎、急性肾损伤和主要心脏不良事件)；4) 进行一项随机对照的试点研究，以确定单次给药一次 一周低血糖风险的抗糖尿病药物可以改善手术患者的血糖控制 潜在的血糖异常(糖尿病前期和新诊断的糖尿病)是发生SH的高危人群。这个 与SH最相关的临床、代谢和炎症信息将用于开发 手术后SH高危患者的风险分层模型识别。 这项建议除了描述重型肝炎的风险因素和潜在机制外，还将加强 多方面的研究培训和职业发展计划是PI成为独立人员所必需的 临床调查员。PI将继续与一支经验丰富的导师和咨询团队合作 拥有住院糖尿病管理、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，以建立 促进跨学科研究合作，推动国际和平研究院学术研究事业的发展。

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.