Background
Telomere shortening has been linked to adverse cardiovascular and metabolic outcomes, including type 2 diabetes mellitus (T2DM). However, limited data exist regarding the relationship between leukocyte telomere length (TL) and subclinical cardiac alterations in asymptomatic T2DM patients, potentially representing an early phase in the development of diabetic cardiomypathy (DbCM).
Purpose
Our aim was to evaluate asymptomatic T2DM patients concerning the effect of telomere shortening on cardiovascular function.
Methods
In this prospective, monocentric study, we examined 116 T2DM patients (mean age 50 ± 4 years) with minimal age variability, free of overt cardiovascular disease (CVD), major diabetic comorbidities, or heart failure symptoms. All participants underwent comprehensive metabolic, echocardiographic, and biochemical characterization, including measurement of leukocyte TL. Associations between TL tertiles and clinical, metabolic, and echocardiographic parameters were assessed using univariate analysis. An unsupervised clustering method (self-organizing maps, SOM) was subsequently applied to identify potential subgroups.
Results
Patients with the lowest TL tertile exhibited significant subclinical diastolic (E and A transmitral flow velocities) and systolic (global and apical longitudinal strain) dysfunction, with diastolic indices showing the strongest discriminatory power. These individuals also demonstrated higher circulating levels of procollagen type I and III propeptides (PICP, PIIINP) and lower plasma MMP-1 and MMP-1/TIMP-1 ratios, suggesting increased extracellular matrix deposition. Among clinical variables, Leukocyte TL was significantly associated with noninvasive fibrosis indices (APRI, FIB-4), reflecting a possible link to metabolic dysfunction-associated steatotic liver disease (MASLD). SOM analysis confirmed these associations between lower TL and cardiac risk factors, T2DM comorbidities and cardiac alterations.
Conclusion
Leukocyte telomere shortening in T2DM patients is associated with subclinical myocardial dysfunction and circulating markers of collagen synthesis, suggesting a distinct pattern of accelerated cardiac aging consistent with the interception of diabetic cardiomyopathy.
