Tear neuropeptide Y as a non-invasive marker of peripheral microvascular complications in type 1 diabetes

Abstract

Aims: To investigate tear neuropeptide Y (NPY) and substance P concentrations in individuals with type 1 diabetes, comparing those with and without both diabetic retinopathy (DR) and peripheral neuropathy.

Methods: This cross-sectional study involved 41 participants with type 1 diabetes and none to moderate DR, and 22 healthy controls. Assessments included clinical ocular surface parameters, quantification of corneal nerve attributes (based on in vivo confocal microscopy imaging), DR grading, and evaluation for small and large fibre neuropathy. Concentrations of NPY and substance P in tear samples were measured using enzyme-linked immunosorbent assay.

Results: Mean (± standard deviation) tear NPY concentrations in participants with type 1 diabetes and length-dependent small fibre neuropathy (SFN) was lower than in controls (10.84 ± 4.10 ng/mL vs 14.72 ± 3.12 ng/mL; p=0.004), but not significantly different from type 1 diabetes participants without SFN (13.39 ± 4.66 ng/mL; p=0.11). Tear NPY levels were lower in individuals with type 1 diabetes and mild/moderate non-proliferative DR (10.44 ± 3.46 ng/mL) compared to none/minimal DR (13.79 ± 4.76 ng/mL; p=0.0005) and controls. In separate linear regression models, both the presence of SFN (β = -0.75, p=0.02) and the presence of mild/moderate DR (β = -0.84, p=0.009) were significantly associated with tear NPY levels relative to controls, after adjusting for participant age, sex, and dry eye disease. There were no inter-group differences for tear substance P concentrations.

Conclusions: Tear NPY has potential utility as an indicator of peripheral microvascular complications associated with type 1 diabetes.

Keywords: Diabetes; Diabetic neuropathy; Diabetic retinopathy; Diabetic sensorimotor polyneuropathy; Diagnostic; Neuropeptide Y; Neuropeptides; Small fibre neuropathy; Substance P; Tear biomarkers.