Interactions of the Osteokines, Glucose/Insulin System and Vascular Risk Networks in Patients With Newly Diagnosed Type 2 Diabetes (VNDS 15)

ABSTRACT Background and Aim 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). Subjects and Methods In 794 drug‐naive, GADA‐negative, newly‐diagnosed T2D patients (mean ± SD age: 59 ± 9.8 years; BMI: 29.3 ± 5.3 kg/m 2 ; 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. Results 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). Conclusion 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.