Retinal neurodegeneration in patients with type 1 diabetes mellitus: the role of glycemic variability

Abstract

Aims: Recent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified.

Methods: To explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants (C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal (N)/temporal (T)/superior (S)/inferior (I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring.

Results: The difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant (F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (-3.9 for noDR and -4.9 for NPDR), without any relevant difference between them (-1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32-15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33-15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index (r = -0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action -1, -2, -4 h (r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL (r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides resulted both independent predictors of increased INL thickness. No correlation was found with HbA1c.

Conclusions: Early structural damage of neuroretina in persons with Type 1 DM patients is related to glucose fluctuations. GV should be addressed, even in the presence of a good metabolic control.

Keywords: Glycemic variability; Retinal neurodegeneration; Type 1 diabetes mellitus.

Fig. 1

Thickness (mean ± SEM) of inner nuclear layer (INL) in the three groups: C (open circle), noDR (closed square) and NPDR (open square). Differences between groups were similar in each quadrant (a), allowing to obtain a global measure of INL (INL-G; b), indicating that both diabetic groups (noDR and NPDR) presented a significant increase (p < 0.01) in thickness versus C group

Fig. 2

Scatter plot between CONGA-2, -4 and INL global thickness in Type 1 DM patients. CONGA-2 (white circles), CONGA-4 (black circles)