Association between alterations of corneal sub-basal nerve plexus analyzed with in vivo confocal microscopy and long-term glycemic variability

Abstract

Purpose: The effect of long-term glycemic variability upon corneal sub-basal nerve plexus (CSNP) morphology analyzed by in vivo confocal microscopy (IVCM) has been poorly investigated in the setting of type 1 diabetes mellitus (T1DM). Our purpose was to analyze the association between morphometric parameters of CSNP and new markers of glycemic variability in a population of patients with T1DM. Methods: Forty patients with T1DM underwent: assessment of diabetic neuropathy (DN); analysis of subcutaneous advanced glycated end-products; IVCM scans of CSNP. The fully automated software ACCMetrics was employed to analyze IVCM images and calculate seven corneal nerve parameters. Data of diabetes duration, mean and standard deviation (SD) of either last-year and all-time glycated hemoglobin (HbA1C) were retrieved. Results: Diabetes duration and all-time SD of HbA1C were independently associated with CNFD (R = –0.26, p = 0.01; R = –0.27, p = 0.047 respectively), CNFL (R = –0.12; p = 0.01; R = –0.17, p = 0.01 respectively) and CNFrD (R = –0.001, p = 0.009; R = –0.002, p = 0.007 respectively). The analysis of the association among IVCM parameters and specific subtypes of DN showed that altered cold sensitivity was independently associated with CNFD (B = –0.24, p = 0.01), CNFL (B = –0.46, p = 0.01) and CNFrD (B = –28.65, p = 0.03). Conclusions: All-time SD of HbA1C and disease duration were found to be independent predictors of damage to CSNP in patients with T1DM.

Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta‐analysis

“…Our sensitivity analysis shows no evidence of significant bias or heterogeneity (Doc S1). This was expected, given that there may be differences in corneal nerve parameters between patients with type 1 and type 2 diabetes 5,7,13 and in relation to HbA1c 66 and glycemic variability 67 , presence of metabolic syndrome 68 and hypertension or hyperlipidemia 7,69 .…”

Evaluation of central corneal epithelial thickness with anterior segment OCT in patients with type 2 diabetes mellitus

“…30 However, different results have been obtained in studies that have evaluated the effect of HbA1c level and the duration of diabetes on SBNP. Pellegrini et al showed that both parameters had an effect on changes in the SBNP, 31 while Kallinikos et al reported that there was no signi cant effect. 32 Lomoriello et al suggested that there was an inverse correlation with the duration of diabetes and the HbA1c level had no signi cant effect 33 while in contrast, Dehghani et al suggested that there was an inverse correlation with the HbA1c level, and there was no signi cant effect of the duration of diabetes.…”

Continuous glucose monitoring reveals a novel association between duration and severity of hypoglycemia, and small nerve fiber injury in patients with diabetes

“…Studies have reported an association between corneal nerve measures and the duration of diabetes (22,23) and HbA1c (24,25) in people with type 1 and type 2 diabetes. Several large clinical trials have shown that improved glycemic control can prevent the development and progression of diabetic neuropathy in type 1 diabetes (26), but not type 2 diabetes (27-30).…”

“…We have demonstrated that increased GV and hypoglycemia detected using CGM are associated with lower CNBD in patients with type 1 and type 2 diabetes. Studies have reported an association between corneal nerve measures and the duration of diabetes ( 22 , 23 ) and HbA1c ( 24 , 25 ) in people with type 1 and type 2 diabetes. Several large clinical trials have shown that improved glycemic control can prevent the development and progression of diabetic neuropathy in type 1 diabetes ( 26 ) but not type 2 diabetes ( 27 , 28 , 29 , 30 ).…”