OR33-08 Clinical, endocrine and hemorheological factors associated with altered RBC aggregability in diabetes

Abstract Disclosure: I. Ebenuwa: None. Background: Diabetic vascular complications are associated with pathophysiological RBC changes including reduced RBC deformability (RBCD): the ability of RBCs to change their shape in the microvasculature and increased red blood cell aggregability (RBCA): the tendency of RBCs to form aggregates. In contrast to RBCD, there is insufficient understanding of the early diabetes-specific changes to RBCA parameters that predispose to vascular complications in populations with diabetes. Due to methodological limitations and inconsistent measurement approaches, data have been conflicting and contradictory findings. Using modern ektacytometry techniques, we investigated altered RBCA parameters in diabetes, relationships between other hemorheological parameters including RBCD and osmotic fragility, and the demographics, clinical, endocrine factors associated with RBCA changes in diabetes. Methods: We conducted an outpatient cross-sectional study of participants with diabetes (N81: 75% type 2 [T2D], 25% type 1 [T1D]) and nondiabetic controls (N78). Clinical history was obtained using standardized forms, fasting samples were collected for standardized clinical laboratory measurements and ektacytometry studies of hemorheological parameters: RBCA, RBCD and osmotic fragility. Major outcomes included between-group differences in three RBCA measures: total aggregation signal (amplitude, AMP); kinetics (time-and-half, T1/2) and aggregation index (AI). Exploratory outcomes assessed subgroup differences based on diabetes type (T1D and T2D), and associated clinical, endocrine and hemorheological factors. Results: Compared with controls, the diabetes cohort had significantly increased AI and faster (decreased) T1/2 (p=0.007 and 0.012 respectively), with more pronounced differences in T2D (p<0.001 for both), but not T1D (p=0.2 and p=0.5 respectively). Aberrant RBCA parameters (increased AI and decreased T1/2) were significantly associated with Black race, older age, male sex, higher BMI, Hgba1c, proteinuria and T2D. Among endocrine parameters, AI was associated with higher HOMA-IR, C-peptide and leptin concentrations, with significantly higher mean values in T2D vs T1D (p<0.001 for all). While AMP was not different in the diabetes cohort or subgroups vs controls, AMP--but not AI and T1/2, was significantly associated with other pathophysiological RBC changes in diabetes: reduced RBCD and osmotic fragility (p<0.001 for both). Conclusions: In this first characterization of aberrant RBCA parameters in diabetes using modern ektacytometry techniques, findings suggest distinct RBCA categories are independently linked to adverse cardiometabolic outcomes that vary based on diabetes type. Data also indicate endocrine dysregulation may underlie pathophysiological RBC changes associated diabetic vascular complications. Presentation: Monday, July 14, 2025