The Relation of Diabetes Complications to a New Interpretation of Glycaemic Variability from Continuous Glucose Monitoring in People with Type 1 Diabetes

Introduction Microvascular and macrovascular complications in type 1 diabetes (T1D) may be linked to endothelial stress due to glycaemic variability. Continuous glucose monitoring systems (CGMs) provide new opportunities to quantify this variability, utilising the amplitude of glucose change summated over time. The aim of this study was to examine whether this determination of glucose variability (GV) is associated with microvascular clinical sequelae. Methods Continuous glucose monitoring values were downloaded for 89 type 1 diabetes mellitus (T1D) individuals for up to 18 months from 2021 to 2023. Data for patient demographics was also taken from the patient record which included Sex, Date of Birth, and Date of Diagnosis. The recorded laboratory glycated haemoglobin (HbA1c) test results were also recorded. The glucose management index (GMI) was calculated from average glucose readings for 18 months using the formula GMI (%) = (0.82−(Average glucose/100)). This was then adjusted to give GMI (mmol/mol) = 10.929 * (GMI (%) − 2.15). Average Glucose Fluctuation (AGF) was calculated by adding up the total absolute change value between all recorded results over 18 months and dividing by the number of results minus one. The % Above Critical Threshold (ACT) was calculated by summing the total number of occurrences for each result value. A cumulative 95% limit was then applied to identify the glucose value that only 5% of results exceeded in the overall population. Using this value, we estimated the percentage of total tests that were above the Critical Threshold (ACT). Results Results for the 89 individuals (44 men and 45 women) were analysed over 18 months. The mean age of participants was 43 years and the mean duration of diabetes was 18 years. A total of 3.22 million readings were analysed, giving an average of 10.3 mmol/L blood glucose. Those with the largest change in glucose from reading to reading, summated over time, showed the greatest change in eGFR of 3.12 ml/min/1.73 m 2 ( p = 0.007). People with a higher proportion of glucose readings > 18 mmol/L showed a fall in eGFR of 2.8 ml/min/1.73 m 2 ( p = 0.009) and experienced higher rates of sight-threatening retinopathy (44% of these individuals) ( p = 0.01) as did 39% of individuals in the highest tertile of glucose levels ( p = 0.008). Conclusion Those individuals with T1D in the highest tertile of reading-to-reading glucose change showed the greatest change in eGFR. Those with a higher proportion of