DIABETIC UPPER EXTREMITY PATHOPHYSIOLOGY, LIMITED JOINT MOBILITY AND DISABILITY

描述（由申请人提供）：本R21提案是对美国国家糖尿病、消化和肾脏疾病研究所（NIDDK） PA-12-157的直接回应，旨在鼓励试点和可行性临床和行为研究，以评估旨在改善糖尿病及其并发症管理的干预措施。众所周知，糖尿病（DM）患者上肢关节和肌肉损伤的发生率非常高，从而导致疼痛和残疾。我们的初步调查数据发现，在门诊糖尿病中心就诊的糖尿病患者中，63%（236人中有149人）报告肩部疼痛或残疾。关节活动受限（LJM）是糖尿病的系统性并发症，被认为是由关节周围结缔组织增厚和僵硬引起的。首先在糖尿病患者的手上观察到，LJM也可能发生在肩部，是严重肩部疼痛和残疾的前兆。葡萄糖和代谢中间体的缩合形成非酶促晚期糖基化终产物（AGEs），被认为是糖尿病患者结缔组织增厚和LJM的主要机制。除了AGE水平过高外，肩部缺乏积极运动可能是导致肩部LJM病因的重要因素。该项目的主要目标是确定AGE积累和肩部运动（胸椎活动范围和“活动计数”）如何相互作用，从而导致肩部LJM、疼痛和残疾，以及由量身定制的拉伸剂量和肩部积极运动组成的干预是否可以减少糖尿病患者的这些问题。一项试点随机对照试验将确定针对性上肢运动计划对肩部抬高、疼痛、该项目将使用一种创新的无创成像测量方法（皮肤固有荧光）作为皮肤中AGE水平的生物标志物，三维运动分析来量化关节关节的有限运动，以及加速度计来量化肩部全天的“活动计数”。该结果将对了解上肢关节和肌肉损伤的代谢和运动相关原因以及是否有目的的运动可以对这些具有严重上肢疼痛和残疾的患者群体的这些限制产生影响具有重要意义。长期目标是了解糖尿病患者肌肉骨骼问题的共同特征，并研究药理学和康复策略，以尽量减少由此产生的疼痛和残疾。

DESCRIPTION (provided by applicant): This R21 proposal is in direct response to PA-12-157 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to encourage pilot and feasibility clinical and behavioral studies to evaluate interventions designed to improve the management of diabetes and it complications. People with diabetes mellitus (DM) are known to have a very high incidence of upper extremity joint and muscle impairments leading to pain and disability. Our preliminary survey data found that 63% (149 of 236) of people with DM attending an outpatient Diabetes Center reported shoulder pain or disability. Limited joint mobility (LJM) is a systemic complication of DM believed to be caused by thickening and stiffness of periarticular connective tissue. First observed in the hands of people with DM, LJM also may occur in the shoulder and be a precursor to severe shoulder pain and disability. Condensation of glucose and metabolic intermediates form non-enzymatic advanced glycation end-products (AGEs) and are thought to be the primary mechanism for this connective tissue thickening and LJM in people with DM. In addition to excessive AGE levels, a lack of active shoulder motion may be an important factor contributing to the etiology of shoulder LJM. The primary goal of this project is to determine how AGE accumulation and shoulder movement (humeral thoracic range of motion and "activity count") interact to contribute to shoulder LJM, pain and disability, and if an intervention consisting of a tailored dose of stretching and active shoulder movement can reduce these problems in people with DM. A pilot randomized controlled trial will determine the effect size of a targeted upper extremity movement program on shoulder elevation, pain, and activity limitations in people with DM. This project will use an innovative and noninvasive imaging measure (skin intrinsic fluorescence) as a biomarker for AGE levels in the skin, three dimensional motion analysis to quantify limited motion of the glenohumeral joint, and accelerometers to quantify shoulder "activity count" throughout the day. The results will have important implications for understanding the metabolic and movement related causes of upper extremity joint and muscle impairments and also if purposeful movements can have an effect on these limitations in this patient group with substantial upper extremity pain and disability. The long term goal is to understand the common denominators of musculoskeletal problems in people with DM and investigate pharmacological and rehabilitative strategies to minimize resultant pain and disability.