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. 2024 Oct;40(7):e3847.
doi: 10.1002/dmrr.3847.

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

Chiara Zusi  1 , Sara Bonetti  1 , Elisabetta Rinaldi  1   2 , Alessandro Csermely  1   2 , Maria Linda Boselli  1 , Daniela Travia  2 , Lorenza Santi  1 , Enzo Bonora  1   2 , Riccardo C Bonadonna  3   4 , Maddalena Trombetta  1   2
Affiliations

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

Chiara Zusi et al. Diabetes Metab Res Rev. 2024 Oct.

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/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.

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.

Keywords: RANKL; diabetes; osteocalcin; osteokines; osteopontin; osteoprotegerin; subclinical atherosclerosis.

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