Disparity in Microvascular and Macrovascular Disease Risk in Diabetics

Abstract

Background: Diabetes and Peripheral Arterial Disease (PAD) are leading causes of non-traumatic amputations and certain populations including Hispanics/LatinX and Native Americans (LXNA) have higher rates of amputations compared to matched White people. Many have attributed this to differential access to health care and the prevalence of DM and PAD in these populations. In addition to these important topics, microvascular disease likely contributes to limb loss and a racial disparity in the prevalence of MVD could exist. Microvascular disease (MVD) describes systemic changes in small vessels (~100 mm diameter) that impair tissue oxygenation and perfusion. Although prevalent but not exclusive to Diabetics, MVD is clinically relevant in limb salvage as it synergistically acts with large vessel peripheral arterial disease to increase the risk of limb loss by 22.7-fold. Clinically, retinopathy and neuropathy are considered markers of MVD, however, these markers act as surrogate endpoints and do not directly provide information on the state of the microvasculature of the feet. In a bid to understand the effect of MVD on the feet of those with PAD, we utilize a non-invasive technology called Spatial Frequency Domain Imaging (SFDI) that has been proven to stratify the severity of clinical microvascular disease by quantifying the amount of hemoglobin (HbT1) in the capillaries of the superficial dermis (1-2mm deep) and tissue oxygenation (StO2) in the dermal microvasculature of the feet. This study aims to evaluate the role of MVD in foot ulcers/limb loss in at-risk populations with PAD. We also seek to determine if the LXNA populations have a higher risk of MVD independent of Diabetes. Lastly, using a non-invasive technology proven to quantify microvascular changes directly in the feet, we aim to assess if a difference exists in the limbs of patients with lower extremity vascular disease (those with a combination of clinical MVD and PAD as compared to those with only PAD). Methods: Three hundred and seven patients (600 lower extremity limbs) were prospectively enrolled at a single institution, Banner University Medicine, Tucson, AZ from 2016- 2023. Clinical MVD was assessed using self-reported retinopathy, self-reported neuropathy, and tools to screen for neuropathy (vibratory tuning fork, 10g monofilament). For analysis with race, only White, Hispanic, and Native Americans were included with the latter categorized as (LtNA). Using logistic regression models, we analyzed the association between race/ethnicity and MVD, adjusting for patient-level covariates. Fisher’s Exact test and Pearson Chi-square tests were used to obtain the odds of surgical outcomes in patients with PAD and MVD and compared to those with only PAD. Wilcoxon rank-sum test was used to determine the difference in SFDI-derived metrics based on vascular disease status. Statistical significance was set as an alpha of less than 0.05. Results: 600 limbs were evaluated (168 LtNA, 404 White). The LtNA group had higher odds of clinical MVD compared to the White group, as determined by a 10g monofilament (aOR: 5.44, 95% CI: 2.77-10.76, p<0.001), self-reported neuropathy (aOR: 4.76, 95% CI: 3.06-7.41, p<0.001), and self-reported retinopathy (aOR: 4.04, 95% CI: 2.29-7.13).Compared to those with only PAD, the combination of PAD and MVD was associated with increased odds of foot ulcers/amputation (MVD determined by 10g monofilament: OR: 8.96, 95%CI: 2.72-29.5, p<0.001, self-reported neuropathy: OR: 30.9, 95% CI: 14.31-66.64, p<0.001, self-reported retinopathy: OR:9.6, 95%CI: 4.0-23.2, p<0.001). Using SFDI, HbT1 was significantly lower in limbs with PAD and MVD compared to limbs with only PAD. (MVD determined by Neuropathy, HbT1: 32 vs 43.5, p<0.001, Retinopathy, HbT1: 32.3 vs 41.3, p=0.003). This shows that dermal microvascular perfusion was worse in patients with a combination of MVD and PAD. Conclusion: This study provides important insights into the association between race/ethnicity and microvascular disease (MVD), and its impact on surgical outcomes in patients with peripheral arterial disease (PAD). Assessing MVD in clinical practice could improve outcomes for patients with lower extremity vascular disease, especially in high-risk racial populations.