Substance P levels may be associated with diabetes-related nerve damage

In subjects with diabetes, levels of substance P—nerve cell signaling molecules found in tears—may be lower than in healthy subjects and were moderately correlated with early damage to the corneal nerves, specifically, corneal nerve fiber density (CNFD), according to a recent pilot study published in Optometry and Vision Science. Substance P may, therefore, be a biomarker for corneal nerve health, and have the potential to be the basis for future noninvasive testing for diabetes-related nerve damage, researchers concluded.

In previous studies, CNFD has been shown to be predictive of diabetes-related damage to the peripheral nerves and the resulting peripheral neuropathy common in diabetic patients. Substance P has several functions: it contributes to wound healing and to the maintenance and nutrition of the cornea.

In this cross-sectional study, researchers sought to assess the relationship between tear film neuropeptide substance P and the structural integrity of the sub-basal nerve plexus in patients with diabetes. They included 17 healthy controls and 9 subjects with diabetes.

Using the flush tears of subjects, they determined the total protein content and substance P concentrations, and assessed corneal nerve morphology using the Heidelberg Retinal Tomograph II with the Rostock Corneal Module in the central cornea. In eight captured images, researchers measured CNFD using ACCMetrics. Finally, they compared differences in the groups using independent samples t-tests, and correlations with Pearson’s correlations.

In the control group, substance P concentrations were significantly higher than in subjects with diabetes (1,473 vs 4,150 pg/mL, respectively; P=0.047). Total protein content did not differ significantly between groups (2.6 vs 3.4 mg/mL, respectively; P=0.262).

Researchers did find, however, that CNFD was significantly lower in subjects with diabetes compared with controls (16.1 vs 21.5 mm/mm², respectively; P=0.041). They also found a moderate correlation between substance P concentrations and CNFD (r=0.48; P=0.01).

"The positive correlation between substance P and corneal nerve density indicates that substance P may be a potential biomarker for corneal nerve health," wrote Maria Markoulli, PhD, MOptom, FAAO, and colleagues, University of New South Wales, Sydney, Australia.