Abstract
Purpose: The purpose of this study was to investigate the association between glycated hemoglobin (HbA1c) levels and retinal sub-layer thicknesses in people with and without diabetes.</p>
Methods: We included 41,453 UK Biobank participants aged 40 to 69 years old. Diabetes status was defined by self-report of diagnosis or use of insulin. Participants were categorized into groups: (1) those with HbA1c <48 mmol/mol were subdivided into quintiles according to normal range of HbA1c; (2) those previously diagnosed with diabetes with no evidence of diabetic retinopathy; and (3) undiagnosed diabetes: >48 mmol/mol. Total macular and retinal sub-layer thicknesses were derived from spectral-domain optical coherence tomography (SD-OCT) images. Multivariable linear regression was used to evaluate the associations between diabetes status and retinal layer thickness.</p>
Results: Compared with participants in the second quintile of the normal HbA1c range, those in the fifth quintile had a thinner photoreceptor layer thickness (-0.33 µm, P = 0.006). Participants with diagnosed diabetes had a thinner macular retinal nerve fiber layer (mRNFL; -0.58 µm, P < 0.001), photoreceptor layer thickness (-0.94 µm, P < 0.001), and total macular thickness (-1.61 µm, P < 0.001), whereas undiagnosed diabetes participants had a reduced photoreceptor layer thickness (-1.22 µm, P = 0.009) and total macular thickness (-2.26 µm, P = 0.005). Compared to participants without diabetes, those with diabetes had a thinner mRNFL (-0.50 µm, P < 0.001), photoreceptor layer thickness (-0.77 µm, P < 0.001), and total macular thickness (-1.36 µm, P < 0.001).</p>
Conclusions: Participants with higher HbA1c in the normal range had marginally thinner photoreceptor thickness, whereas those with diabetes (including undiagnosed diabetes) had meaningfully thinner retinal sublayer and total macular thickness.</p>
Translational Relevance: We showed that early retinal neurodegeneration occurs in people whose HbA1c levels are below the current diabetes diagnostic threshold; this might impact the management of pre-diabetes individuals.</p>