Association of Leukocyte Telomere Length and HbA1c with Post-COVID-19 Syndrome in Type 2 Diabetes: A Cross-Sectional Pilot Study

Anton Matviichuk¹Viktoriia Yerokhovych¹Yeva Ilkiv¹Dmytro Krasnienkov^2,3Veronika Korcheva^2,4Oleksandr Gurbych^3,5Anna Shcherbakova⁶Pavlina Botsun⁶Tetyana Falalyeyeva^4,6Oksana Sulaieva^6,7Nazarii Kobyliak^1,6*

• ¹Bogomolets National Medical University, Kyiv, Ukraine
• ²Institute of Gerontology Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
• ³Blackthorn AI, London, United Kingdom
• ⁴Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
• ⁵Lviv Polytechnic National University, Lviv, Ukraine
• ⁶Medical Laboratory CSD, Kyiv, Ukraine
• ⁷Kyiv Medical University, Kyiv, Ukraine

Introduction: Leukocyte telomere length is considered as a promising prognostic marker associated with COVID-19 severity, adverse outcomes (hospital admission, need for critical care, respiratory support), and mortality. However, telomere length contribution in post-COVID-19 syndrome (PCS) development is unclear.Aim: to evaluate the association between telomere shortening and PCS course of type 2 diabetes patients (T2D) and uncover whether telomere length is linked with clinical phenotype, gender, and biological age.In this cross-sectional study, 66 T2D patients after COVID-19 were enrolled. Patients were divided into 2 groups depending on PCS development: PCS group (n=44) and patients who didn't develop PCS (n=22) in 6 months after COVID-19 infection. To determine the relative telomere length standardized method proposed by Cawthon et al was used. We developed a range of machine learning models for PCS prediction. The models underwent training utilizing a crossvalidation approach, and internal validation was conducted.We observed significantly lower mean of telomere length in T2D patients with PCS as compared to those without it (1.09±0.19 and 1.28±0.24; p=0.001). In sub analysis, shorter telomere was observed in females and patients of older age in both groups. The mean telomere length didn't differ significantly among clinical phenotypes of PCS (p=0.193). The best model generated for PCS prediction was the gradient boosting machine (GBM) which AUC comprised 0.753. The most influential variables across the top 10 models included telomere length, HbA1c, vitamin D3, waist circumference, ApoA1, C peptide, ApoB, COVID-19 severity, duration of T2D, IL-6, cholesterol, BMI, and age. Leukocyte telomere length and HbA1c exhibited significantly higher impacts compared to other features.Conclusions: Shorter telomere length and higher HbA1c levels were significantly associated with the presence of PCS in our cohort of individuals with T2D. These factors may represent potential biomarkers that warrant further investigation.