Li Jiang, An Yuxiao, Qin Jian, Mohamad Noor Shafini, Ramli Izzad
Faculty of Health Sciences, Universiti Teknologi MARA, Shah Alam, Malaysia.
The Second Affiliated Hospital of Shandong First Medical University, Taian, China.
Front Med (Lausanne). 2025 May 9;12:1530462. doi: 10.3389/fmed.2025.1530462. eCollection 2025.
Type 2 diabetes mellitus (T2DM) is often accompanied by bone metabolic disorders and cognitive impairment, forming an interactive network through metabolic derangements, oxidative stress, and inflammatory responses. Hyperglycemia and insulin resistance disrupt bone remodeling leading to osteoporosis while simultaneously impairing cognition via blood-brain barrier damage and neuroinflammation. Osteogenic factors like osteocalcin may bidirectionally regulate glucose metabolism and brain function, suggesting that "bone-brain axis" dysregulation could be a potential mechanism underlying cognitive impairment in T2DM. This study aims to characterize cognitive function patterns in T2DM patients with bone metabolic abnormalities and their clinical correlations, providing a basis for multisystemic interventions.
The general clinical data, osteocalcin (OC), glycosylated hemoglobin (HbA1c), bone mineral density (BMD), and the Montreal Cognitive Assessment (MoCA) scores of 50 patients with T2DM were collected. According to whether cognitive impairment occurred or not, one-way ANOVA was performed to analyze the correlation between cognitive and clinical indicators, BMD and OC. Multiple linear regression analysis was performed with cognition and bone density as dependent variables and other factors as independent variables.
T2DM subjects were grouped according to bone mass. The osteoporosis group had the lowest MoCA score and bone density, followed by the osteopenia group. There were 16 cases (16/17 94.12%) of cognitive impairment in the osteoporosis group, 13 cases (13/17 76.47%) of cognitive impairment in the osteopenia group, and 3 cases (3/16 18.75%) of cognitive impairment in the normal bone mass group. Compared with the normal cognitive group, the MoCA score, OC measurement and BMD of the patients in the cognitive impairment group were lower ( < 0.05). BMD ( = 0.686, = 0.000), OC ( = 0.756, = 0.000) are positively correlated with MoCA score. OC ( = 0.690, = 0.000) and Age ( = -0.032, = 0.045) are positively correlated with BMD. Multivariate linear regression analysis found that with cognition as the dependent variable, the decrease in BMD ( = 0.028) and OC ( = 0.000) aggravated the occurrence of cognitive impairment; with BMD as the dependent variable, the decline in cognition ( = 0.028) and OC ( = 0.029) aggravated the decrease in BMD.
T2DM, osteoporosis, and cognitive impairment form pathological connections through metabolic disorders, chronic inflammation, and bidirectional regulatory networks of the "bone-brain axis," with osteocalcin serving as a key mediator that maintains bone remodeling balance while also exerting cross-domain regulation over central insulin signaling and synaptic plasticity. Understanding these interactive mechanisms provides a basis for developing combined screening models integrating bone density and cognitive assessments, and promotes multidisciplinary collaborative interventions across endocrinology, orthopedics, and neurology to improve overall outcomes for T2DM patients.
2型糖尿病（T2DM）常伴有骨代谢紊乱和认知障碍，通过代谢紊乱、氧化应激和炎症反应形成一个交互网络。高血糖和胰岛素抵抗会破坏骨重塑，导致骨质疏松，同时通过血脑屏障损伤和神经炎症损害认知功能。骨钙素等成骨因子可能双向调节葡萄糖代谢和脑功能，这表明“骨-脑轴”失调可能是T2DM患者认知障碍的潜在机制。本研究旨在描述伴有骨代谢异常的T2DM患者的认知功能模式及其临床相关性，为多系统干预提供依据。
收集50例T2DM患者的一般临床资料、骨钙素（OC）、糖化血红蛋白（HbA1c）、骨密度（BMD）及蒙特利尔认知评估（MoCA）评分。根据是否发生认知障碍，采用单因素方差分析分析认知与临床指标、BMD和OC之间的相关性。以认知和骨密度为因变量，其他因素为自变量进行多元线性回归分析。
T2DM受试者按骨量分组。骨质疏松组的MoCA评分和骨密度最低，其次是骨量减少组。骨质疏松组有16例（16/17，94.12%）认知障碍，骨量减少组有13例（13/17，76.47%）认知障碍，正常骨量组有3例（3/16，18.75%）认知障碍。与认知正常组相比，认知障碍组患者的MoCA评分、OC测量值和BMD较低（P<0.05）。BMD（r = 0.686，P = 0.000）、OC（r = 0.756，P = 0.000）与MoCA评分呈正相关。OC（r = 0.690，P = 0.000）和年龄（r = -0.032，P = 0.045）与BMD呈正相关。多元线性回归分析发现，以认知为因变量，BMD（β = 0.028）和OC（β = 0.000）的降低加重了认知障碍的发生；以BMD为因变量，认知能力下降（β = 0.028）和OC（β = 0.029）加重了BMD的降低。
T2DM、骨质疏松和认知障碍通过代谢紊乱、慢性炎症和“骨-脑轴”的双向调节网络形成病理联系，骨钙素作为关键介质，在维持骨重塑平衡的同时，还对中枢胰岛素信号和突触可塑性发挥跨域调节作用。了解这些交互机制为开发整合骨密度和认知评估的联合筛查模型提供了依据，并促进内分泌学、骨科和神经科的多学科协作干预，以改善T2DM患者的整体预后。
