Carotid atherosclerosis: An independent risk factor for small fiber nerve dysfunction in patients with type 2 diabetes mellitus

Abstract

Aims/introduction: To explore whether carotid atherosclerosis is an independent risk factor for small fiber nerve dysfunction in type 2 diabetes mellitus patients.

Materials and methods: A total of 247 type 2 diabetes patients from Nanjing Drum Tower Hospital received carotid ultrasonography and quantitative sensory testing, including cold and warm detection thresholds, and some patients received cold and heat pain detection thresholds, respectively. According to the results of quantitative sensory testing, patients were divided into normal small fiber nerve function (NSF) and small fiber nerve dysfunction (SFD) group. Meanwhile, patients were divided into the non-carotid atherosclerosis group, carotid intimal thickening, unilateral carotid atherosclerosis and bilateral carotid atherosclerosis group. The correlation between carotid ultrasonography with quantitative sensory testing parameters was analyzed by SPSS 26.0.

Results: First, the incidence rate of SFD increased significantly in patients with carotid atherosclerosis (72.2%, P < 0.001) especially in bilateral carotid atherosclerosis (81.7%, P < 0.001). Second, compared with the NS group, the carotid intima-media thickness in SFD was thicker (P = 0.018) and the size of atherosclerotic plaque was larger (P < 0.001). In addition, the cold detection threshold decreased (P < 0.001), whereas the warm detection threshold (P < 0.001) and heat pain detection threshold (P < 0.001) increased as aggravation of carotid atherosclerosis. In the correlation analysis, the size of atherosclerotic plaque presented a positive correlation with the warm detection threshold (r = 0.476, P < 0.001) and heat pain detection threshold (r = 0.213, P < 0.001), but presented a negative correlation with the cold detection threshold (r = -0.239, P < 0.01). Furthermore, carotid atherosclerosis (odds ratio 2.326, P = 0.017), especially bilateral carotid atherosclerosis (odds ratio 5.042, P = 0.001), was an independent risk factor for SFD (P < 0.05).

Conclusions: Carotid atherosclerosis was significantly associated with quantitative sensory testing and found to be an independent risk factor for small fiber nerve dysfunction in type 2 diabetes patients.

Keywords: Carotid atherosclerosis; Quantitative sensory testing; Small fiber neuropathy; Type 2 diabetes mellitus.

Figure 1

The incidence rate of small fiber nerve dysfunction in different groups, (a) Incidence rate of small fiber nerve dysfunction group (SFD) and normal small fiber nerve function group (NSF) patients in carotid atherosclerosis (CA) group and non‐carotid atherosclerosis (NCA) group. (b) Incidence rate of SFD and NSF patients in the unilateral carotid atherosclerosis (UCA) group and bilateral carotid atherosclerosis (BCA) group.

Figure 2

Quantitative sensory testing parameters in different groups of carotid atherosclerosis. Independent t‐tests and Mann–Whitney U‐tests were used to analyze the difference between two groups. One‐way anova were used to compare the statistical significance of normally distributed variable and Kruskal–Wallis H‐tests were used to analyze abnormal distributions among three groups. The Bonferroni test was used to avoid the multiple comparison problem. BCA, bilateral carotid atherosclerosis; CDT, cold detection threshold; CPT, cold pain detection threshold; HPT, heat pain detection threshold; NCA, non‐carotid atherosclerosis; UCA, unilateral carotid atherosclerosis; WDT, warm detection threshold.

Figure 3

Forest graph in searching that carotid atherosclerosis as the independent risk factors for small fiber dysfunction. Model 1: unadjusted; model 2: adjusted for age, diabetic duration, glycosylated hemoglobin, creatinine, osteocalcin, beta C‐terminal telopeptide of type I collagen and folic acid. CI, confidence interval; OR, odds ratio. BCA, bilateral carotid atherosclerosis; CIT, carotid intimal thickening; NCA, non‐carotid atherosclerosis; UCA, unilateral carotid atherosclerosis.