Relationship between Insulin Resistance and Circulating Stem and Progenitor Cells in Newly-diagnosed Youth-onset Type...

To investigate the relationship between insulin resistance (IR) and circulating stem cells and endothelial progenitor cells (EPCs) in youth-onset type 2 diabetes mellitus (T2DM).

A total of 392 newly diagnosed T2DM patients aged 12-25 years were enrolled. General data, medical history, and anthropometric indices were collected. Blood glucose, lipid profiles, and glycated hemoglobin (HbA1c) were measured. IR was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR). Circulating stem cells (CD34+ cells) and EPCs (CD34+ kinase insert domain receptor [KDR]+ cells) were quantified via flow cytometry.

When stratified by HOMA-IR tertiles, significant differences were observed across groups in CD34⁺ stem cells, CD34⁺ KDR⁺ EPCs, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (all P < 0.05 or P < 0.01). No significant differences were detected in age, sex, fasting plasma glucose (FPG), or HbA1c. Correlation analysis demonstrated inverse associations of CD34⁺ stem cells (r = -0.453) and CD34⁺ KDR⁺ EPCs (r = -0.531) with HOMA-IR (both P < 0.01), while positive correlations were observed with BMI (-0.327; -0.342), SBP (-0.261; -0.246), DBP (-0.213; -0.269), TG (-0.182; -0.199), TC (-0.221; -0.258), and LDL-C (-0.234; -0.293). HDL-C showed a positive correlation (r = 0.137, r = 0.247, both P < 0.05). No significant associations were found with age, sex, FPG, or HbA1c. In multivariate regression analysis, HOMA-IR remained independently associated with reduced CD34⁺ stem cells (adjusted β = 1.846, 95% CI: 0.723-4.209, P < 0.05) and CD34⁺ KDR⁺ EPCs (adjusted β = 1.985, 95% CI: 0.856-4.843, P < 0.05) after adjusting for BMI, blood pressure, and lipid parameters.

Our results indicate that insulin resistance plays a crucial, reversible role in the development of early vascular damage among adolescents with type 2 diabetes. This highlights the importance of implementing early interventions aimed at improving insulin sensitivity in this vulnerable population.

HOMA-IR was independently associated with reduced levels of circulating stem cells and EPCs in youth-onset type 2 diabetes, indicating its role as an independent risk factor for vascular endothelial dysfunction in this population.