Hoda Gad1, Einas Elgassim1, Ibrahim Mohammed1,2, Ahmad Yaser Alhaddad3, Hussein Ahmed Hussein Zaky Aly4, John-John Cabibihan3, Abdulaziz Al-Ali4, Kishor Kumar Sadasivuni5, Aliyaa Haji1, Neila Lamine1, Adnan Khan1, Ioannis N. Petropoulos1, Georgios Ponirakis1, Alise Kalteniece6, Maryam Ferdousi6, Shazli Azmi6, Uazman Alam7,8,9, Wajeeha Abuhelaiqa10, Amin Jayyousi10, Dabia AlMohanadi10, Khaled Baagar10, Rayaz A. Malik1,6*
Background/Aim: Continuous glucose monitoring (CGM) has revealed that glycemic variability (GV) and low time in range (TIR) are associated with albuminuria and retinopathy. We have investigated the relationship between CGM metrics and highly sensitive markers of nerve pathology using corneal confocal microscopy (CCM) 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). Participants with diabetes underwent CGM for 4 consecutive days.
Results: CNBD was significantly lower in patients with high 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 below range (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 severe hypoglycemia (<54 mg/dl) (25.0 (19.8-41.7) vs. 35.4 (28.1-44.8); P=0.04). Duration in hyperglycemia and severe hyperglycemia did not correlate with CNFD (P>0.05), CNBD (P>0.05), CNFL (P>0.05) or IWL (P>0.05), but duration in hypoglycemia correlated with CNBD (r=-0.342, P=0.031).
Conclusions: Greater glucose variability and duration in hypoglycemia, rather than hyperglycemia are associated with nerve fiber loss in diabetes.