Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Biostatistics Program, Office of Clinical Research Support, Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Cardiovasc Diabetol. 2024 Oct 18;23(1):370. doi: 10.1186/s12933-024-02453-2.
Reduced red blood cell deformability (RBCD) is associated with diabetic vascular complications, but early pathophysiological RBC changes and predictive demographic and clinical factors in populations with diabetes are unclear. An understanding of early diabetes-specific RBC changes associated with impaired RBCD is essential in investigating mechanisms that predispose to diabetic vascular complications.
We conducted an outpatient cross-sectional study of participants in a well-controlled diabetes cohort (N81) and nondiabetic controls (N78) at the National Institutes of Health. First, between-group differences in RBCD measures were assessed with shear stress-gradient ektacytometry. Differences in structural RBC parameters were assessed using osmotic gradient ektacytometry and NaCl osmotic fragility. Functional RBC changes were assessed using hemoglobin-oxygen dissociation: p50.
All shear-stress gradient RBCD measures were significantly altered in the diabetes cohort vs. nondiabetic controls, even after adjustment for confounding covariates (p < 0.001). Adjusted for diabetes-status and demographic factors, significant predictors of reduced RBCD included older age, Black race, male gender, hyperglycemia, and vascular complications (all p < 0.05). Reduced RBCD was also associated with aberrant osmotic-gradient parameters, with a left-shift on osmotic gradient profile indicative of dehydrated RBCs in diabetes. A structure-function relationship was observed with reduced RBCD associated with reduced osmotic fragility (P < 0.001) and increased hemoglobin-oxygen dissociation (P < 0.01).
Findings suggest impaired RBCD incurs similar demographic and clinical risk factors as diabetic vascular disease, with early pathophysiological RBC changes indicative of disordered RBC hydration in diabetes. Findings provide strong evidence for disordered oxygen release as a functional consequence of reduced RBCD.
NCT00071526.
红细胞变形能力降低（RBCD）与糖尿病血管并发症有关，但糖尿病患者中早期病理生理 RBC 变化和预测性人口统计学及临床因素尚不清楚。了解与 RBC 变形能力降低相关的糖尿病特异性 RBC 早期变化对于研究易患糖尿病血管并发症的机制至关重要。
我们在国立卫生研究院对一个血糖控制良好的糖尿病队列（N81）和非糖尿病对照（N78）的门诊患者进行了一项横断面研究。首先，使用切应力梯度 ektacytometry 评估 RBC 变形能力的组间差异。使用渗透梯度 ektacytometry 和 NaCl 渗透脆性评估 RBC 结构参数差异。使用血红蛋白氧解离：p50 评估 RBC 功能变化。
与非糖尿病对照组相比，糖尿病组的所有切应力梯度 RBC 变形能力测量值均显著改变，即使在校正混杂协变量后（p < 0.001）。在校正糖尿病状态和人口统计学因素后，RBCD 降低的显著预测因素包括年龄较大、黑种人、男性、高血糖和血管并发症（均 p < 0.05）。RBCD 降低还与异常的渗透梯度参数相关，糖尿病患者的渗透梯度曲线左移表明 RBC 脱水。观察到结构-功能关系，RBCD 降低与渗透脆性降低（P < 0.001）和血红蛋白氧解离增加（P < 0.01）相关。
研究结果表明，RBCD 受损与糖尿病血管疾病具有相似的人口统计学和临床危险因素，糖尿病患者的早期病理生理 RBC 变化表明 RBC 水合作用紊乱。研究结果为 RBC 变形能力降低导致的氧释放功能障碍提供了有力证据。
NCT00071526。
