Effects of Age, Sex and Systemic Inflammation on Coronary and Peripheral Vascular Function in Elderly Individuals with Type 2 Diabetes

Eva Rickers (Köln)1, J. Dushay (Boston, MA)2, R. V. Shah (Nashville, TN)3, V. Murthy (Boston, MA)4, E. Wang (Boston MA)5, Y. Zhang (Boston MA)5, R. Blankstein (Boston, MA)6, E. V. Gervino (Boston, MA)7, M. Jerosch-Herold (Boston, MA)4, A. Veves (Boston MA)5

1Universitätsklinikum Köln Neurologie Köln, Deutschland; 2Beth Israel Deaconess Medical Center Division of Endocrinology Boston, MA, USA; 3Vanderbilt University Division of Cardiology Nashville, TN, Deutschland; 4Brigham and Women’s Hospital Department of Radiology Boston, MA, USA; 5Beth Israel Deaconess Medical Center Rongxiang Xu Center for Regenerative Therapeutics, Microcirculation Lab Boston MA, USA; 6Brigham and Women’s Hospital Division of Cardiology Boston, MA, USA; 7Beth Israel Deaconess Medical Center Division of Cardiology Boston, MA, USA


Background: Inflammation, aging, and type 2 diabetes mellitus (T2DM) play an important role in the development of microcirculatory and cardiovascular dysfunction, yet the exact interplay of these factors remains unclear. Our aim was to evaluate the effects of age, sex, and systemic inflammation on coronary and peripheral vascular function in elderly individuals with and without T2DM and to determine if optimal medical management of cardiovascular risk factors in T2DM patients preserves coronary function.

Methods and Results: 133 individuals aged ≥65, 54 with and 79 without type 2 diabetes mellitus (T2DM), were closely matched for baseline metabolic characteristics and analyzed in this cross-sectional study. Inflammatory phenotyping (serum and skin biopsy) and non-invasive cardiovascular assessments, including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) for myocardial blood flow (MBF) at rest and during hyperemia, left ventricular (LV) structure, and function, as well as flow-mediated (FMD) and nitroglycerin-induced vasodilation (NID), were conducted. Correlation and cluster analysis of serum biomarkers were conducted to assess systemic inflammation's role in cardiovascular health.

No significant differences were observed between patients with and without T2DM for baseline CMR measurements, as well as a wide range of inflammatory cytokines and skin biopsy inflammation markers. For the entire cohort, hyperemic myocardial blood flow correlated negatively with WBC (r=-0.29; P=0.014). WBC counts were elevated in the T2DM group (p = 0.004), but this did not translate into impaired coronary microcirculatory function in patients with T2DM. T2DM patients had higher BMI (p = 0.11) and lower total cholesterol and LDL (p < 0.0001). Statin and antihypertensive medication use was more frequent among individuals with T2DM compared to controls (p < 0.0001 for both).

Hierarchical clustering based on cytokines identified a patient group with a proinflammatory profile, including upregulation of proinflammatory (sVCAM-1, GDF-15, MPO) and downregulation of anti‑inflammatory biomarkers (IL-2, IL-10, and IL-13), which was linked to reduced hyperemic myocardial perfusion (1.63 ± 0.36 vs. 2.05 ± 0.53 ml/min/g; p=0.002). 

Several sex specific differences were noted. Females presented with a higher rest myocardial perfusion (p=0.049).Myocardial blood flow during hyperemia was lower in males with T2DM (p = 0.039) compared to males without T2DM, but there was no T2DM-related difference in females (p=0.872). Only Men with T2DM showed significantly lower FMD (p=0.052) and NID (p<0.001) compared to men without T2DM. Females with T2DM displayed lower peak VO2 values compared to females without T2DM (p = 0.03). Peak VO2 correlated negatively with fasting glucose, suggesting glycemic impact on cardiopulmonary function.

Conclusion: Elderly patients with well-controlled T2DM appear not to be at increased risk for coronary dysfunction compared to non-diabetic counterparts. However, serum biomarkers indicative of inflammatory phenotypes provided insights into coronary dysfunction risk, independent of T2DM status. Age appeared to be a more critical determinant of inflammation than T2DM when glycemic levels and comorbidities were well-controlled, with sex-specific differences noted. These findings underscore the potential of inflammatory profiling in stratifying cardiovascular risk and tailoring management in elderly populations with T2DM.

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