Insulin resistance in individuals without type 2 diabetes is associated with large arteries stiffening

Abstract Background Insulin resistance (IR) is a hallmark of metabolic disorders such as type 2 diabetes mellitus (T2DM) (1). Evidence indicates that even individuals who appear metabolically healthy can harbor insullin resistance, which significantly contributes to cardiovascular risk before diagnosis of T2DM is established (2). A principal measure of vascular health is arterial stiffness, commonly evaluated using carotid femoral pulse wave velocity (cf-PWV). Elevated cf-PWV is known to be a strong independent predictor of cardiovascular events (3). Recently, it has been shown that aortic stiffening precedes diagnosis of T2DM (4). However, if IR in individuals without T2DM impacts on large artery stiffening is currently incompletely understood. Purpose To evaluate the influence of insulin resistance on large artery stiffening in patients without type 2 diabetes Methods As part of the PHaRAo trial; (Phenotyping Heterogeneity and Regionality of the Aorta) we recruited 64 cardiovascularly healthy volunteers aged 20 to 80 years. Participants underwent vascular phenotyping including applanation tonometry (SphygmoCor, PulsePen) to evaluate cf-PWV and cardiac magnetic resonance imaging (MRI) incorporating 4D flow analyses to determine regional aortic flow patterns, aortic distensibility and cardiac function. Insulin resistance was evaluated based on the homeostatic model assessment of insulin resistance (HOMA-IR) and glucose status was measured by HbA1c, fasting glucose and 2-hour oral glucose tolerance test. Participants were grouped according to established thresholds of HOMA-IR index ( 2.5: no insulin resistance, 2.5-5: possible insulin resistance, 5: insulin resistance). Results Baseline characteristics of the different groups are shown in Figure 1. All participants had normal HbA1c-values and did not differ significantly in age, BMI, fasting glucose and 2h plasma glucose. Figure 2 shows measurements of the aortic input, conductance and output function according to HOMA-IR index. Individuals with HOMA-IR index 5 showed a significant reduction in aortic distensibility along the ascending and descending aorta combined with a decrease in cf-PWV compared to individuals with HOMA-IR index 2.5 (Figure 2B). Maximal Wall Shear Stress (MWSS) and augmentation index were not significantly affected. Regarding aortic input function, a significant reduction in EDV, SV and EF was observed in individuals with HOMA-IR index 5 compared to HOMA-IR index 2.5 (Figure 2A). No significant difference in aortic output function could be observed (Figure 2C). Conclusions Our findings suggest that insulin resistance as defined by HOMA-IR index in otherwise cardiovascular healthy individuals without established T2DM is associated with arterial stiffening and may contribute to the eventual onset of cardiovascular diseases. Further research is needed to understand the pathophysiology and prognostic implications of aortic stiffening in these patients.Figure 1. Figure 2.