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Open access

Hoda Gad, Einas Elgassim, Ibrahim Mohammed, Ahmad Yaser Alhaddad, Hussein Ahmed Hussein Zaky Aly, John-John Cabibihan, Abdulaziz Al-Ali, Kishor Kumar Sadasivuni, Aliyaa Haji, Neila Lamine, Adnan Khan, Ioannis N Petropoulos, Georgios Ponirakis, Alise Kalteniece, Maryam Ferdousi, Shazli Azmi, Uazman Alam, Wajeeha Abuhelaiqa, Amin Jayyousi, Dabia AlMohanadi, Khaled Baagar, and Rayaz A Malik

Objective

Continuous glucose monitoring (CGM) has revealed that glycemic variability and low time in range are associated with albuminuria and retinopathy. We have investigated the relationship between glucose metrics derived from CGM and a highly sensitive measure of neuropathy using corneal confocal microscopy in participants with type 1 and type 2 diabetes.

Methods

A total of 40 participants with diabetes and 28 healthy controls underwent quantification of corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and inferior whorl length (IWL) and those with diabetes underwent CGM for four consecutive days.

Results

CNBD was significantly lower in patients with high glycemic variability (GV) compared to low GV (median (range) (25.0 (19.0–37.5) vs 38.6 (29.2–46.9); P = 0.007); in patients who spent >4% compared to <4% time in level 1 hypoglycemia (54-69 mg/dL) (25.0 (22.9–37.5) vs 37.5 (29.2–46.9); P = 0.045) and in patients who spent >1% compared to <1% time in level 2 hypoglycemia (<54 mg/dL) (25.0 (19.8–41.7) vs 35.4 (28.1–44.8); P = 0.04). Duration in level 1 hypoglycemia correlated with CNBD (r = –0.342, P = 0.031). Duration in level 1 (181–250 mg/dL) and level 2 (>250 mg/dL) hyperglycemia did not correlate with CNFD (P > 0.05), CNBD (P > 0.05), CNFL (P > 0.05) or IWL (P > 0.05).

Conclusions

Greater GV and duration in hypoglycemia, rather than hyperglycemia, are associated with nerve fiber loss in diabetes.