Continuous glucose monitoring in critically ill patients

描述（由申请人提供）：在非糖尿病和糖尿病患者中，高血糖和胰岛素抵抗通常使危重疾病复杂化。即使是中度高血糖症，由于有诱发低血糖症的风险，在常规上未用胰岛素进行急性治疗的水平，也会导致发病率和死亡率。最近在危重患者中进行的一项随机临床试验表明，严格控制血糖浓度（80 - 110 mg/dL）的强化胰岛素治疗可使发病率和死亡率大幅降低40%以上（从8.0%降至4.6%），但与5.0%的严重低血糖（血糖浓度< 40 mg/dL）发生率相关。因此，在重症患者中，理想的无创连续血糖监测对于指导胰岛素输注以控制高血糖和避免低血糖将是非常宝贵的。为此，基于低相干干涉测量的光学相干断层扫描（OCT），一种灵敏地检测从组织相干散射的光子的高分辨率光学技术，是非常有前途的。我们已经开发出一种新型的基于OCT的葡萄糖传感器，该传感器精确地、连续地和非侵入性地测量线性地伴随血糖浓度增加的组织光散射的减少。在过去的两年中，在PA-99-036（“糖尿病内分泌和代谢的试点和可行性计划”）下的NIDDK R-21资助的支持下，我们对新型葡萄糖传感器进行了初步的动物和临床研究。我们的研究表明：1）随着血糖浓度的增加，皮肤和口腔粘膜中OCT信号斜率的急剧和线性减小;以及2）通过优化探测的组织区域的尺寸，OCT信号斜率测量的准确性得到显著提高。拟议项目的目标是：（1）在动物研究中进一步完善葡萄糖传感器;（2）在正常受试者和重症患者的临床研究中验证所得传感器。该项目的成功实施将产生一种连续、无创和准确的葡萄糖传感器，这将大大有助于降低危重患者的死亡率和发病率。

DESCRIPTION (provided by applicant): In both nondiabetic and diabetic patients, hyperglycemia and insulin resistance commonly complicate critical illness. Even moderate hyperglycemia, at levels that conventionally have not been treated acutely with insulin because of the risk of inducing hypoglycemia, contributes to morbidity and mortality. A recent randomized clinical trial in critically ill patients demonstrated that intensive insulin therapy to tightly control blood glucose concentration (80 - 110 mg/dL) substantially reduced morbidity and mortality by more than 40% (from 8.0% to 4.6%) but was associated with a 5.0% incidence of severe hypoglycemia (glucose concentration < 40 mg/dL). Therefore, in critically ill patients, continuous glucose monitoring, ideally noninvasive, would be invaluable to guide insulin infusion to both control hyperglycemia and avoid hypoglycemia. For this purpose, optical coherence tomography (OCT) based on low-coherence interferometry, a high-resolution optical technique that sensitively detects photons coherently scattered from tissue, is highly promising. We have developed a novel, OCT-based glucose sensor that precisely, continuously and noninvasively measures the decrease of tissue light scattering that linearly accompanies increases of blood glucose concentration. During the past two years, supported by an NIDDK R-21 grant under the PA-99-036 ("Pilot and Feasibility Program in Diabetes Endocrinology and Metabolism"), we performed preliminary animal and clinical studies of the novel glucose sensor. Our studies demonstrated: 1) a sharp and linear decrease of the OCT signal slope in skin and oral mucosa as blood glucose concentration increased; and 2) substantial improvement of accuracy of the OCT signal slope measurement by optimizing the dimensions of the probed tissue area. The goals of the proposed project are: (1) to further refine the glucose sensor in animal studies; and (2) to validate the resulting sensor in clinical studies in normal subjects and critically ill patients. Successful implementation of the project will produce a continuous, noninvasive, and accurate glucose sensor that will substantively contribute to reduced mortality and morbidity in critically ill patients.