Carotid arterial wall inflammation in peripheral artery disease is augmented by type 2 diabetes: a cross-sectional study

Abstract

Background: Patients with peripheral artery disease (PAD) are at increased risk of secondary events, which is exaggerated in the presence of type 2 diabetes mellitus. Diabetes is associated with a systemic pro-inflammatory state. We therefore investigated the cumulative impact of PAD and type 2 diabetes on carotid arterial wall inflammation. As recent data suggest a detrimental role of exogenous insulin on cardiovascular disease, we also included a group of insulin users.

Results: ¹⁸F-fluorodeoxyglucose positron emission tomography with computed tomography (¹⁸F-FDG PET/CT) imaging showed increased carotid arterial wall inflammation, assessed as target-to-background ratio (TBR), in PAD patients without diabetes (PAD-only: n = 11, 1.97 ± 0.57) compared with matched controls (n = 12, 1.49 ± 0.57; p = 0.009), with a significant further TBR increase in PAD patients with type 2 diabetes (PAD-DM, n = 23, 2.90 ± 1, p = 0.033 vs PAD-only). TBR of insulin users (n = 12, 3.31 ± 1.14) was higher compared with patients on oral medication only (n = 11, 2.44 ± 0.76, p = 0.035), despite comparable PAD severity (Fontaine stages), BMI and CRP. Multivariate regression analysis showed that Hba1c and plasma insulin levels, but not dose of exogenous insulin, correlated with TBR.

Conclusions: Concurrent diabetes significantly augments carotid arterial wall inflammation in PAD patients. A further increase in those requiring insulin was observed, which was associated with diabetes severity, rather than with the use of exogenous insulin itself.

Keywords: Diabetes mellitus; Imaging; Inflammation; Insulin; Peripheral vascular disease.

Fig. 1

Quantification of ¹⁸F-FDG uptake as the target to background ratio (TBR) in the whole (a, d) carotid arteries, as well as the maximum TBR (b, e) and TBR in the most diseased segment (MDS) (c, f) revealed increased uptake in all segments in PAD subjects compared with healthy controls, and a further increase in PAD subjects with concomitant Diabetes Mellitus (a-c). Within Diabetic subjects, insulin dependent subjects (IDDM) had more severe arterial wall inflammation compared with non-insulin dependent subjects (NIDDM) (d-f). P values are adjusted for age and gender. *p < 0.05, **p < 0.01, ***p < 0.001

Fig. 2

Target to Background ratio (TBR_mean) significantly correlated to fasting glucose levels (Correlation coefficient: 0.845, p < 0.001) (a). Fasting insulin correlated significantly to TBR_mean (b) but dose of exogenous insulin did not (Insulin: Correlation coefficient: 0.814, p < 0.001; Exogenous insulin dose: Correlation coefficient: 0.235, p = 0.486). Insulin resistance, measured by HOMA-IR, stongly associated with TBR_mean (Correlation coefficient:, 0.876, p < 0.001)