Background and Aims

Telomere lengths have been associated with type 2 diabetes and coronary artery disease (CAD). The prevalence of CAD in type 1 diabetes (T1DM) is high with an unknown association with telomere lengths. We aimed to search for associations of CAD and leukocyte telomere lengths (LTLs), and the longevity factors growth-differentiating factor (GDF)11 and sirtuin (SIRT)1, the latter which may regulate insulin sensitivity and attenuate autoimmunity.

Methods

Hundred-and-five cases with long-term T1DM and 75 controls* were included (mean age 62, 42% females), 88 cases and 60 controls completed computed tomography coronary angiography (CTCA). Obstructive CAD was defined as either previous coronary heart disease or > 50% stenosis on CTCA. LTLs and gene expression of SIRT1 and GDF11 were relatively quantified (RQ) in circulating leukocytes by PCR.

Results

LTLs were shorter and SIRT1 lower expressed in T1DM subjects vs. controls: 0.97 (0.82, 1.15) medians (24, 75 percentiles) vs 1.08 (0.85, 1.29) and 0.88 (0.65, 1.14) vs. 1.01 (0.78, 1.36), respectively, both p<0.02. In all, obstructive CAD (n=44) associated with shorter LTLs compared to no-CAD; 0.95 (0.79, 1.11) vs. 1.05 (0.84, 1.23), p=0.042. In the diabetes group, previous CAD (n=15) was associated with lower SIRT1 and GDF11 expression (p=0.036 and p=0.007), respectively.

Conclusions

Obstructive CAD in T1DM patients associated with shorter LTLs. Together with lower SIRT1 and GDF11 expression in T1DM patients with previous CAD, these results may indicate a role of LTLs, SIRT1 and GDF11 in the development of CAD in T1DM.

* Holte et al, J. Diabetes. Comp. 2019;33:383-389