Metabolic determinants of torque teno virus load across the diabetes spectrum: insights from a cross-sectional analysis

Abstract

Torquetenovirus (TTV) is a ubiquitous non-pathogenic DNA virus whose replication mirrors immune competence. We profiled TTV viremia (TTVv) across type 1 diabetes (T1D), type 2 diabetes (T2D), and non-diabetes (ND) controls and assessed clinical associations. Cross-sectional, multicentre analysis of 485 individuals (T2D n. 277; T1D n. 61; ND n. 147). Plasma TTV-DNA was quantified by real-time PCR. Clinical/metabolic variables were harmonized across cohorts. Associations with TTVv were tested with uni- and multivariable models adjusting for age, sex, body mass index (BMI), glycated haemoglobin (HbA1c), and antidiabetic therapies. TTVv was detectable in 74.4%, with higher prevalence in T2D (79.0%) and T1D (73.8%) versus ND (69.0%). Age was an independent predictor. In T2D, unlike T1D, TTVv correlated negatively with BMI and HbA1c; those with poor control (HbA1c ≥ 8%) had significantly lower TTVv. Dipeptidyl peptidase-4 inhibitors (DPP-IVi) were independently associated with both TTVv presence and higher titers. Among T2D, individuals with TTVv < 4.0 log copies/ml were more often obese, female, and less frequently treated with DPP-IVi. TTVv is more prevalent and higher in diabetes, yet lower with poor glycaemic control and obesity, suggesting a directionality paradox. TTVv may index immunometabolic balance in diabetes; longitudinal and mechanistic studies are warranted.