Bone as an endocrine organ regulates metabolic processes independently of mineral metabolism through the production/release of proteins collectively named 'osteokines'. Relevant connections were reported between the insulin/glucose system, calcification of the atherosclerotic plaque, and several osteokines. We aimed to test the hypothesis that the osteokine network could be involved in beta-cell function, insulin sensitivity, and vascular damage in a cohort of people with newly diagnosed type 2 diabetes (T2D). In 794 drug-naive, GADA-negative, newly-diagnosed T2D patients (mean±SD age: 59±9.8years; BMI: 29.3±5.3kg/m2; HbA1c: 6.6±1.3%) we assessed: plasma concentration of osteocalcin (OCN), osteopontin (OPN),RANKL, and its putative decoy receptor osteoprotegerin (OPG); insulin sensitivity (SI) by hyperinsulinemic euglycemic clamp; beta cell function (BCF), estimated by OGTT minimal modelling and expressed as derivative (DC) and proportional (PC) control. Echo-doppler of carotid and lower limb arteries were also performed in 708 and 701 subjects, respectively. OCN, RANKL and OPG were significantly associated with PC (p<0.02); OCN was positively related to DC (p=0.018). OPG was associated with lower IS (p<0.001). Finally, the higher RANKL levels, the greater was the severity of atherosclerosis in common carotid artery (p<0.001). Increased OPG and OPN concentrations were related to subclinical atherosclerosis in peripheral arteries of lower limbs (p=0.023 and p=0.047, respectively). These data suggest that, in patients with newly diagnosed T2D, the osteokine network crosstalks with the glucose/insulin system and may play a role in modulating the atherosclerotic process.
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