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

Abstract

AimsRecent 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.MethodsTo 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.ResultsThe 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.ConclusionsEarly 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.

Fasting plasma glucose variability is an independent risk factor for diabetic retinopathy and diabetic macular oedema in type 2 diabetes: An 8‐year prospective cohort study

“…Perrot et al found that glucose fluctuation would increase pulsatile ocular blood flow, which may cause damage to the endothelium of the choroidal vessels and resulting in retinal hypoxia in patients with type 2 diabetes. Picconi et al also showed that early structural damage of neuroretina was related to glucose fluctuation in type 1 diabetes. These prior studies are consistent with the present study showing that higher fasting glucose variability was correlated with the development and progression of DR.…”

Beyond Hyperglycemia, Evidence for Retinal Neurodegeneration in Metabolic Syndrome

“…Increased triglyceride levels were reported to be associated with increased INL thickness in type 1 DM subjects with early retinal degeneration. 41 Moreover, fenofibrate (FA) therapy was shown to lower the progression of DRP by reducing triglyceride levels in type 2 DM subjects. 42,43 However, the protective effect of FA was reported to be independent of its lipid-lowering effects.…”

Glycaemic variability: The under‐recognized therapeutic target in type 1 diabetes care

“…GV has been associated with a number of markers of vascular complications, independent of average glucose control. For example, GV has been associated with retinal thickening and neurodegenerative defects in the retina that were independent of HbA1c . It has also been associated with markers of autonomic cardiovascular (CV) function such as heart rate variability, particularly during the night .…”

“…For example, GV has been associated with retinal thickening and neurodegenerative defects in the retina that were independent of HbA1c. 27,28 It has also been associated with markers of autonomic cardiovascular (CV) function such as heart rate variability, particularly during the night. 29,30 More recently, CGMdefined GV has been associated with the presence of CV autonomic neuropathy.…”