The Effect of HbA1C Variability and Lipid Profile on Carotid Intima-Media Thickness and Flow-mediated Dilatation in Children and Adolescents with Type 1 Diabetes Mellitus

Background: Type 1 Diabetes Mellitus (T1DM) is one of the most significant factors contributing to the increased risk of cardiovascular diseases. The increase in cardiovascular diseases itself is triggered by atherosclerosis. Atherosclerosis can be detected early through carotid intima-media thickness (CIMT) and flow-mediated dilation (FMD) examination. The result of CIMT and FMD can be affected by several factors, such as HbA1c variability and lipid profile. Objectives: This study aimed to determine the influence of HbA1c variability and lipid profile on CIMT and FMD levels found in pediatric patients with T1DM treated at Saiful Anwar General Hospital of Malang. Methods: The study utilized a cross-sectional design that included 82 participants with Type 1 Diabetes Mellitus who were routinely treated at the pediatrics outpatient clinic in Saiful Anwar General Hospital of Malang from January to July 2019 and December 2021 to January 2022 and were willing to undergo CIMT and FMD examinations which are then taken for lipid profile and serial HbA1c tests. At least six HbA1c measurements within 18 months were included. HbA1c Variability Score (HVS), HbA1c-coefficient variation (HbA1c-CV), and HbA1c-standard deviation (HbA1c-SD) were used to evaluate variability. Results: There was no significant correlation between HDL (ρ=-0,029; p=0,796), LDL (ρ=-0.213; p=0.055), TG (ρ=-0.179; p= 0.107), and total cholesterol (ρ=-0.182; p= 0.101) with FMD according to the test results. There was a positive correlation amongst LDL (ρ=0,318; p=0,004) and total cholesterol levels (ρ=0,230; p=0,038) with IMT. The correlation coefficient between HbA1C variability and FMD as evaluated by HVS was-0.498 (ρ =0.000; p=0.05), equal to the value that serves as the correlation coefficient between HbA1c-SD (ρ=-0.467; p=0.000) and HbA1c-CV (ρ =-0.400; p=0.000). Furthermore, there is a significant positive correlation between IMT and HbA1c variability using HVS (ρ= 0.455; p = 0.000), HbA1c-SD (ρ= 0.434; p=0.000), and HbA1c-CV (ρ= 0.325; p=0.003). The linear regression analysis revealed that the three variables with the greatest influence on FMD were HVS (R = 0.398), LDL (R = 0.316), and HbA1c-SD (R = 0.293). The three most impactful variables on IMT were HVS (R = 0.468), LDL (R = 0.268), and total cholesterol (R = 0.198). It is known that by using this model, the combination of HbA1c variability and lipid profile contributes to 25.1% on FMD and 34.5% on IMT. Conclusion: Variability of HbA1c and lipid profile (LDL and total cholesterol) has effects on increasing the CIMT levels and decreasing the FMD of the brachial artery in children with T1DM.