Continuous glucose monitoring defined glucose variability is associated with cardiovascular autonomic neuropathy in type 1 diabetes

Abstract

Background The purpose of this study was to establish the association between continuous glucose monitoring (CGM)‐defined glycaemic variability (GV) and cardiovascular autonomic neuropathy (CAN) in type 1 diabetes independent of mean glucose and to examine the relative contribution of each internationally standardized CGM parameter to this association. Materials and methods This study included 80 adults with type 1 diabetes who underwent 3‐day CGM and autonomic function tests within 3 months. The degree of association between internationally standardized CGM parameters and CAN, defined as at least two abnormal parasympathetic tests or the presence of orthostatic hypotension, were analysed by logistic regression, receiver operating characteristics (ROC), and dominance analysis. Results A total of 36 subjects (45.0%) were diagnosed with CAN. When adjusted with mean glucose and clinical risk factors of CAN, standard deviation, coefficient of variation, mean amplitude of glycaemic excursion, percent time in level 1 (glucose 54‐69 mg/dL) and level 2 (glucose < 54 mg/dL) hypoglycaemia, area under the curve in level 2 hypoglycaemia, low blood glucose index, high blood glucose index, and percent time in glucose 70 to 180 mg/dL were independently associated with CAN. Multivariable ROC analysis and dominance analysis revealed the highest relative contribution of percent time in level 2 hypoglycaemia to the independent associations between CGM parameters and presence of CAN. Conclusions CGM‐defined GV was associated with CAN independent of mean glucose in adults with type 1 diabetes. Among internationally standardized CGM parameters, those describing the degree of level 2 hypoglycaemia were the most significant contributors to this association.

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

“…29,30 More recently, CGMdefined GV has been associated with the presence of CV autonomic neuropathy. 31 GV strongly correlates with excitability markers of altered motor and sensory axonal function, but acute glucose levels (6-12 mmol/L) do not. 32 As such, GV may contribute to the development of CV autonomic dysfunction in adults with T1DM.…”

“…It has also been associated with markers of autonomic cardiovascular (CV) function such as heart rate variability, particularly during the night . More recently, CGM‐defined GV has been associated with the presence of CV autonomic neuropathy . GV strongly correlates with excitability markers of altered motor and sensory axonal function, but acute glucose levels (6‐12 mmol/L) do not .…”

The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes: A systematic review

“…This review contains six eligible studies, of which four cross-sectional [38][39][40][41] and two prospective cohort studies with a follow-up of 3 and 10 years 42,43 . The sample size of the cross-sectional studies varied between 20-80 patients and the cohort studies included respectively 41 and 1375 patients 42,43 .…”

“…Considering the methods for determination of GV, five studies used CGM [38][39][40][41][42] for a duration between 1-6 days, while one study used 7-point capillary blood glucose profiles at 3 months intervals 43 . SD and MAGE of glucose values were the most studied parameters of GV, determined in five studies 38,[40][41][42][43] . Hypoglycaemic indices (LBGI, AUC hypo and %time in hypo) were reported in three studies 39,40,42 .…”

“…SD and MAGE of glucose values were the most studied parameters of GV, determined in five studies 38,[40][41][42][43] . Hypoglycaemic indices (LBGI, AUC hypo and %time in hypo) were reported in three studies 39,40,42 . COV glucose and M-value (two studies); CONGA, MODD and MAG (one study) were used less frequently.…”