Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus

IntroductionType 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...

Full description

Saved in:
Bibliographic Details
Main Authors: Jiang Li, Yuxiao An, Jian Qin, Noor Shafini Mohamad, Izzad Ramli
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1530462/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850040160416169984
author Jiang Li
Jiang Li
Yuxiao An
Jian Qin
Jian Qin
Noor Shafini Mohamad
Izzad Ramli
author_facet Jiang Li
Jiang Li
Yuxiao An
Jian Qin
Jian Qin
Noor Shafini Mohamad
Izzad Ramli
author_sort Jiang Li
collection DOAJ
description IntroductionType 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.MethodsThe 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.ResultsT2DM 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 (P < 0.05). BMD (r = 0.686, P = 0.000), OC (r = 0.756, P = 0.000) are positively correlated with MoCA score. OC (r = 0.690, P = 0.000) and Age (r = −0.032, P = 0.045) are positively correlated with BMD. Multivariate linear regression analysis found that with cognition as the dependent variable, the decrease in BMD (P = 0.028) and OC (P = 0.000) aggravated the occurrence of cognitive impairment; with BMD as the dependent variable, the decline in cognition (P = 0.028) and OC (P = 0.029) aggravated the decrease in BMD.ConclusionT2DM, 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.
format Article
id doaj-art-8562789d531b4be4b3db0584f41f5f66
institution DOAJ
issn 2296-858X
language English
publishDate 2025-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Medicine
spelling doaj-art-8562789d531b4be4b3db0584f41f5f662025-08-20T02:56:09ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-05-011210.3389/fmed.2025.15304621530462Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitusJiang Li0Jiang Li1Yuxiao An2Jian Qin3Jian Qin4Noor Shafini Mohamad5Izzad Ramli6Faculty of Health Sciences, Universiti Teknologi MARA, Shah Alam, MalaysiaThe Second Affiliated Hospital of Shandong First Medical University, Taian, ChinaThe Second Affiliated Hospital of Shandong First Medical University, Taian, ChinaFaculty of Health Sciences, Universiti Teknologi MARA, Shah Alam, MalaysiaThe Second Affiliated Hospital of Shandong First Medical University, Taian, ChinaMedical Imaging, Faculty of Health and Life Sciences, Exeter, United KingdomCollege of Computing, Informatics and Mathematics, Universiti Teknologi MARA, Shah Alam, MalaysiaIntroductionType 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.MethodsThe 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.ResultsT2DM 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 (P < 0.05). BMD (r = 0.686, P = 0.000), OC (r = 0.756, P = 0.000) are positively correlated with MoCA score. OC (r = 0.690, P = 0.000) and Age (r = −0.032, P = 0.045) are positively correlated with BMD. Multivariate linear regression analysis found that with cognition as the dependent variable, the decrease in BMD (P = 0.028) and OC (P = 0.000) aggravated the occurrence of cognitive impairment; with BMD as the dependent variable, the decline in cognition (P = 0.028) and OC (P = 0.029) aggravated the decrease in BMD.ConclusionT2DM, 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.https://www.frontiersin.org/articles/10.3389/fmed.2025.1530462/fulltype 2 diabetes mellitusabnormal bone metabolismcognitive impairmentbone mineral densityosteocalcin
spellingShingle Jiang Li
Jiang Li
Yuxiao An
Jian Qin
Jian Qin
Noor Shafini Mohamad
Izzad Ramli
Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus
Frontiers in Medicine
type 2 diabetes mellitus
abnormal bone metabolism
cognitive impairment
bone mineral density
osteocalcin
title Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus
title_full Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus
title_fullStr Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus
title_full_unstemmed Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus
title_short Study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus
title_sort study on the correlation between abnormal bone metabolism and cognitive impairment in type 2 diabetes mellitus
topic type 2 diabetes mellitus
abnormal bone metabolism
cognitive impairment
bone mineral density
osteocalcin
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1530462/full
work_keys_str_mv AT jiangli studyonthecorrelationbetweenabnormalbonemetabolismandcognitiveimpairmentintype2diabetesmellitus
AT jiangli studyonthecorrelationbetweenabnormalbonemetabolismandcognitiveimpairmentintype2diabetesmellitus
AT yuxiaoan studyonthecorrelationbetweenabnormalbonemetabolismandcognitiveimpairmentintype2diabetesmellitus
AT jianqin studyonthecorrelationbetweenabnormalbonemetabolismandcognitiveimpairmentintype2diabetesmellitus
AT jianqin studyonthecorrelationbetweenabnormalbonemetabolismandcognitiveimpairmentintype2diabetesmellitus
AT noorshafinimohamad studyonthecorrelationbetweenabnormalbonemetabolismandcognitiveimpairmentintype2diabetesmellitus
AT izzadramli studyonthecorrelationbetweenabnormalbonemetabolismandcognitiveimpairmentintype2diabetesmellitus