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

Abstract

Objective: Continuous glucose monitoring 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 continuous glucose monitoring 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, corneal nerve branch density, corneal nerve fiber length and inferior whorl length and those with diabetes underwent continuous glucose monitoring for 4 consecutive days. Results: Corneal nerve branch density was significantly lower in patients with high glucose variability compared to low glucose variability (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 corneal nerve branch density (r=-0.342, P=0.031). Duration in level 1 (181-250 mg/dl) and level 2 (>250mg/dl) hyperglycemia did not correlate with corneal nerve fiber density (P>0.05), corneal nerve branch density (P>0.05), corneal nerve fiber length (P>0.05) or inferior whorl length (P>0.05). Conclusions: Greater glucose variability and duration in hypoglycemia, rather than hyperglycemia are associated with nerve fiber loss in diabetes.

FT3/FT4 ratio in a certain range identified as an independent protective factor for glycemic variability in patients with type 2 diabetes

“…Diabetic retinopathy (DR) as an important prevalent blind-causing ophthalmic disease [5] , is also strongly associated with glycemic variability [6] . Hypoglycemia has also been associated with cardiovascular events [7] , cognitive disorders [8] , and worsening nerve ber loss [9] . All of these severe consequences contribute to poor quality of life and reduced lifespan in middle-aged and elder individuals.…”

Longitudinal Studies of Wearables in Patients with Diabetes: Key Issues and Solutions

“…Blood glucose measurement most commonly relies on a finger prick with a drop of blood on a disposable test strip, which can cause discomfort, pain, and scarring [19]. Continuous glucose monitoring (CGM) is a minimally invasive technology that measures interstitial glucose with a time lag with blood glucose and varying degrees of reliability, accuracy, and precision [20][21][22][23][24].…”