Department of Medicine, University of Verona, Verona, Italy.
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Hospital Trust of Verona, Verona, Italy.
Diabetes Metab Res Rev. 2024 Oct;40(7):e3847. doi: 10.1002/dmrr.3847.
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 ± 9.8 years; BMI: 29.3 ± 5.3 kg/m; 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.
骨骼作为一个内分泌器官，通过产生/释放统称为“骨代谢因子”的蛋白质，独立于矿物质代谢来调节代谢过程。胰岛素/葡萄糖系统、动脉粥样硬化斑块的钙化以及几种骨代谢因子之间存在相关联系。我们旨在验证以下假说，即骨代谢因子网络可能参与新诊断的 2 型糖尿病（T2D）患者的β细胞功能、胰岛素敏感性和血管损伤。
在 794 名未经药物治疗、GADA 阴性、新诊断的 T2D 患者（平均年龄 ± 标准差：59 ± 9.8 岁；BMI：29.3 ± 5.3 kg/m；HbA1c：6.6 ± 1.3%）中，我们评估了以下指标：骨钙素（OCN）、骨桥蛋白（OPN）、RANKL 及其假定的诱饵受体骨保护素（OPG）的血浆浓度；通过高胰岛素正葡萄糖钳夹评估胰岛素敏感性（SI）；通过 OGTT 最小模型评估β细胞功能（BCF），并表示为衍生（DC）和比例（PC）控制。在 708 名和 701 名受试者中，分别进行了颈动脉和下肢动脉的回声多普勒检查。
OCN、RANKL 和 OPG 与 PC 显著相关（p < 0.02）；OCN 与 DC 呈正相关（p = 0.018）。OPG 与较低的 IS 相关（p < 0.001）。最后，RANKL 水平越高，颈总动脉粥样硬化程度越严重（p < 0.001）。较高的 OPG 和 OPN 浓度与下肢外周动脉的亚临床动脉粥样硬化有关（p = 0.023 和 p = 0.047）。
这些数据表明，在新诊断的 T2D 患者中，骨代谢因子网络与葡萄糖/胰岛素系统相互作用，并可能在调节动脉粥样硬化过程中发挥作用。
