Glycemic variability may be associated with early neuroretinal changes in pediatric patients with type 1 diabetes without microvascular complications.
In a 3-year longitudinal study involving 25 patients aged 10 to 20 years with type 1 diabetes and 18 age-matched healthy controls, researchers used spectral-domain optical coherence tomography (OCT) to measure neuroretinal layer thickness, focusing on layers from the retinal nerve fiber layer through the outer nuclear layer. They evaluated changes in retinal structure over time and associations with continuous glucose monitoring (CGM)-derived measures of glycemic variability and time in range, HbA1c, and peripheral and autonomic neuropathic measures. The patients had HbA1c levels below 9.5%, had used continuous subcutaneous insulin infusion and CGM for at least 12 months, had no diabetic retinopathy at enrollment, and had a mean diabetes duration of 6.7 years. The researchers conducted assessments at baseline and at 12, 24, and 36 months, with complete peripheral and autonomic neurologic evaluations performed at 36 months.
At baseline, inner retinal nerve fiber layer thickness was lower among the patients with type 1 diabetes compared with controls (20 μm vs. 21 μm). While the inner plexiform, inner nuclear, outer plexiform, and outer nuclear layers were also thinner, the differences were not statistically significant. During follow-up, the inner ganglion cell layer and outer plexiform layer showed statistically significant thinning among patients with type 1 diabetes.
Greater glycemic variability was associated with thinner retinal layers, particularly the inner nuclear and outer plexiform layers, even after adjustment. Greater time in range was associated with thicker retinal layers. Across the 3-year follow-up, greater glycemic variability was also associated with greater structural variation in layers rich in nerve fibers and Müller cells, including the retinal nerve fiber, inner plexiform, inner nuclear, and outer plexiform layers.
By contrast, the researchers found no statistically significant correlations between HbA1c levels and macular layer thickness. Higher glycemic variability and lower time in range were associated with inner retinal thinning during follow-up, while greater glycemic variability was associated with less stable retinal structure.
At 36 months, changes in the inner plexiform layer correlated with Michigan Neuropathy Screening Instrument questionnaire scores, outer plexiform layer changes correlated with both questionnaire scores and systolic blood pressure changes during orthostatic testing, and outer nuclear layer changes correlated with monofilament testing.
The findings were limited by the small sample size and the highly selected population of patients with good glycemic control and no microvascular complications at enrollment. The researchers did not include corneal confocal microscopy. The observed associations could not establish that glycemic variability caused retinal neurodegeneration or that retinal changes predict subsequent diabetic neuropathy.
“Further longitudinal evaluation is required to demonstrate if neuroretinal nerve damage can serve as a non-invasive predictive marker of diabetic neuropathy,” wrote lead study author Marika Menduni, of the Unit of Endocrinology and Diabetology at the Ospedale Isola Tiberina-Gemelli Isola in Italy, and colleagues.
The study authors reported no conflicts of interest.
Source: Scientific Reports
