Background and Aims

Vascular aging in obesity and type 2 diabetes (T2D) is associated with progressive vascular calcification, an independent predictor of morbidity

and mortality. Pathways for vascular calcification modulate bone matrix deposition, regulating calcium deposits. We investigated

the association between biomarkers of vascular calcification and vasodilator function in obesity or T2D, and whether antidiabetic

therapies impact those markers.

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Methods

Circulating levels of proteins involved in vascular calcification, as osteopontin (OPN), osteoprotegerin (OPG)), regulated on activation, normal T cell expressed and secreted (RANTES), fetuin-A were measured in lean subjects, individuals with metabolically healthy obesity (MHO), patients with metabolically unhealthy obesity (MUO) or T2D. Vasodilator function was assessed by infusion of ACh and sodium nitroprusside (SNP).

Results

Circulating levels of OPN were higher in the MUO/T2D group than in lean subjects (P 0.05); OPG and RANTES were

higher in MUO/T2D group than in the other groups (both P 0.001); fetuin-A was not different between groups (P 0.05); vasodilator

responses to either ACh or SNP were impaired in both MUO/T2D and MHO compared with lean subjects (all P 0.001). In patients with

T2D who were enrolled in the intervention trial, antidiabetic treatment with glyburide, metformin, or pioglitazone resulted in a significant

reduction of circulating OPG (P 0.001), without changes in the other biomarkers and vasodilator responses (all P 0.05).

Conclusions

In conclusion,obese patients with MUO/T2D have elevated circulating OPN, OPG, and RANTES; in these patients, antidiabetic treatment reduces

only circulating OPG. Further study is needed to better understand the mechanisms of vascular calcifications in obesity and diabetes.