Subendocardial Viability Ratio predicts Cardiorespiratory Fitness in insulin resistant humans: Impact of Type 2 Diabetes and Sex

Objective: To determine central hemodynamic predictors of cardiorespiratory fitness (CRF) in insulin resistant individuals with and without type 2 diabetes (T2D). Hypothesis: Central hemodynamic measures predict CRF [measured via peak oxygen uptake (VO 2peak )]. Methods: We prospectively enrolled fourteen adults with (n=7M/7F; age:50.1±7.6 yrs; BMI: 31.2 ±3.1 kg/m 2 ; HbA1c: 6.8 ± 0.8%) and twenty-seven adults without T2D (n=9M/18F; age:44.4±9.01 yrs; BMI: 34.3 ±3.8 kg/m 2 ; HbA1c: 5.6 ±0.33%). All participants were sedentary and without clinically or echocardiographically evident cardiovascular disease (CVD). All participants had a graded VO 2peak test on either a cycle ergometer or treadmill and central hemodynamic variables including augmentation index (AI), pulse wave velocity (PWV), aortic systolic pressure (SYS), aortic diastolic pressure (DIA), aortic pulse pressure (PP), mean arterial pressure (MAP), and the subendocardial viability ratio (SEVR) were determined. Linear mixed models were used to examine differences in VO 2peak , where age and BMI were random factors, and sex and group were fixed factors. Partial correlations were used to assess the associations between CRF and central hemodynamic variables, independent of age. A multivariate model was created based on the significant associations between CRF and variables of interest to create a prediction model of CRF. Data are presented as mean ± SE. Results: Participants with T2D had VO 2peak (23.6 ± 1.1 mL/kg/min) similar to those without T2D VO 2peak (23.8± 0.80 mL/kg/min, p=0.89). There was a main effect of sex, where males had significantly higher VO 2peak compared to females (26.0±1.0 vs 21.4±0.8 mL/kg/min p=0.0006). There was a trending group by sex interaction, where males without T2D had significantly higher VO 2peak than females without T2D (27.1±1.3 vs 20.5±0.9 mL/kg/min p=0.07). Among all central hemodynamic parameters examined, only SEVR was significantly associated with CRF, independent of age (r=0.55, p=0.0002), with a much stronger association in males (r=0.72, p=0.002) than in females (r=0.38, p=0.07).The relationship remained similar between individuals with (r=0.60, p=0.03) and without T2D (r=0.53, p=0.006). In a multivariate linear regression model that included age, sex, BMI, and SEVR as explanatory variables, all parameters were independently associated with CRF (β=27.2, F= 9.6, p<0.0001), and this model identified 46% of the variance in CRF (Adjusted R 2 =46.1%, p<0.0001). The model with SEVR alone explained 25% of the variance in CRF (Adjusted R 2 =25.6%, p<0.0001). Conclusion: SEVR, which is defined as the diastolic to systolic pressure-time integral ratio and an index of myocardial perfusion / oxygen supply and demand, independently predicts CRF in a population of individuals with insulin resistance, particularly in men. As CRF is a predictor of both all cause and CVD mortality, and reduced SEVR is associated with unfavorable CVD risks, identifying the contributors to CRF and SEVR is critical to developing targeted interventions to enhance overall cardiovascular health in individuals with insulin resistance. NIH R01DK102359, R01DK124344, R01DK125330, 5T32DK007646 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.