Low serum levels of bone turnover markers are associated with the presence and severity of diabetic retinopathy in patients with type 2 diabetes mellitus

An, Yingli; Liu, Simo; Wang, Wenbo; Dong, Huan; Zhao, Wenying; Ke, Jing; Zhao, Dong

doi:10.1111/1753-0407.13089

Cited by 15 publications

(12 citation statements)

References 51 publications

(110 reference statements)

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“…Serum bone turnover markers can be used to assess bone loss or formation more sensitive than BMD ( 53 – 55 ). Previous studies demonstrated reduced bone resorption and formation in T2D individuals ( 56 – 58 ), suggesting that hyperglycemia and AGEs crosslinking may impair the function of osteoblasts and osteoclasts, thereby inhibiting bone formation and promoting bone resorption. Correlation analysis in our study also confirmed the AGEs level was positively correlated with glycemic parameters including FBG, HbA1c, HOMA-IR, bone resorption marker S-CTX, and negatively correlated with bone formation marker PINP in postmenopausal T2D patients.…”

Section: Discussionmentioning

confidence: 96%

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

Gao

Liu²,

Pan³

et al. 2022

Front. Endocrinol.

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ObjectiveThe objective of this study was to analyze the quantitative association between advanced glycation end products (AGEs) and adjusted FRAX by rheumatoid arthritis (FRAX-RA) in postmenopausal type 2 diabetic (T2D) patients. The optimal cutoff value of AGEs was also explored, which was aimed at demonstrating the potential value of AGEs on evaluating osteoporotic fracture risk in postmenopausal T2D patients.MethodsWe conducted a cross-sectional study including 366 postmenopausal participants (180 T2D patients [DM group] and 186 non-T2D individuals [NDM group]). All the subjects in each group were divided into three subgroups according to BMD. Physical examination, dual-energy x-ray absorptiometry (DXA), and serum indicators (including serum AGEs, glycemic parameters, bone turnover markers and inflammation factors) were examined. The relationship between FRAX-RA, serum laboratory variables, and AGEs were explored. The optimal cutoff value of AGEs to predict the risk of osteoporotic fracture was also investigated.ResultsAdjusting the FRAX values with rheumatoid arthritis (RA) of T2D patients reached a significantly increased MOF-RA and an increasing trend of HF-RA. AGEs level was higher in the DM group compared to the NDMs, and was positively correlated with MOF-RA (r=0.682, P<0.001) and HF-RA (r=0.677, P<0.001). The receiver operating characteristic curve analysis revealed that the area under the curve was 0.804 (P<0.001), and the optimal AGEs cut-off value was 4.156mmol/L. Subgroup analysis for T2D patients revealed an increase in TGF-β, IL-6 and SCTX in the osteoporosis group, while a decreased PINP in the osteoporosis group compared to the other two subgroups. AGEs were positively associated with FBG, HbA1c, HOMA-IR, S-CTX, IL-6 and TGF-β in T2D patients, and negatively associated with PINP.ConclusionsRA-adjusted FRAX is a relevant clinical tool in evaluating fracture risk of postmenopausal T2D patients. Our study analyzed the relationship between AGEs and FRAX-RA, and explored the threshold value of AGEs for predicting fracture risk in postmenopausal T2D patients. AGEs were also associated with serum bone turnover markers and inflammation factors, indicating that the increasing level of AGEs in postmenopausal T2D patients accelerated the expression of inflammatory factors, which led to bone metabolism disorders and a higher risk of osteoporotic fractures.

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Section: Discussionmentioning

confidence: 96%

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

Gao

Liu²,

Pan³

et al. 2022

Front. Endocrinol.

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“…After adjusting these factors, our results were similar to those of previous studies. An et al 49 found that serum OC and β-CTX levels were significantly lower among 117 patients with DR than among 168 patients without DR. However, they observed that serum P1NP and β-CTX levels were inversely associated with DR risk, which was different from our results.…”

Section: Discussionmentioning

confidence: 99%

Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study

Hou¹,

Hou²,

Nie³

et al. 2023

DMSO

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The aim of this study was to evaluate the association of bone turnover markers (BTMs) with type 2 diabetes mellitus (T2DM) and microvascular complications. Methods: A total of 166 T2DM patients and 166 non-diabetic controls matched by gender and age were enrolled. T2DM patients were subclassified into groups based on whether they had diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Clinical data including demographic characteristics and blood test results [serum levels of osteocalcin (OC), N-terminal propeptide of type 1 procollagen (P1NP), and β-crosslaps (β-CTX)] were collected. Logistic regression and restrictive cubic spline curves were performed to examine the association of BTMs with the risk of T2DM and microvascular complications. Results: After adjusting for family history of diabetes, sex and age, an inverse association was observed between elevated serum OC levels [ORð95%CIÞ ¼ 0:18 0:09; 0:35 ð Þ, p < 0.001] and increased serum P1NP levels ORð95%CIÞ ¼ 0:23 0:12; 0:44 ð Þ, p < 0.001] with the risk of T2DM. Moreover, there was an inverse linear association of serum OC and P1NP levels with the risk of T2DM. However, β-CTX was not associated with T2DM. Further analysis showed a nonlinear association between OC and the risk of DR, while P1NP and β-CTX were not correlated with DR. Serum concentrations of BTMs were not associated with the risks of DPN and DKD. Conclusion: Serum OC and P1NP levels were negatively correlated with T2DM risk. Particularly, serum OC levels were associated with DR risk. Given that BTMs are widely used as markers of bone remodeling, the present finding provides a new perspective for estimating the risk of diabetic microvascular complications.

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“…The close interaction between bone and other organ, including CNS is a research hotspot in recent years [ 27 ]. Bone is emerging as a multi-faceted endocrine organ by secreting several osteokines including OCN [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Osteocalcin ameliorates cognitive dysfunctions in a mouse model of Alzheimer’s Disease by reducing amyloid β burden and upregulating glycolysis in neuroglia

Shan

Deng

et al. 2023

Cell Death Discov.

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Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the accumulation of amyloid β peptides (Aβ) and impaired glucose metabolism in the brain. Osteocalcin (OCN), an osteoblast-derived protein, has been shown to modulate brain functions but whether it has any effect on AD is undetermined. In this study, daily intraperitoneal injection of OCN for 4 weeks ameliorated the anxiety-like behaviors and cognitive dysfunctions in the APP/PS1 transgenic AD mice model, as shown in the increased entries into the central area in open field test, the increased time and entries into open arms in elevated plus maze test, the increased time spent in the light chamber in light-dark transition test, as well as the reduced escape latency and the increased preference for target quadrant in Morris water maze test. Aβ burden in the hippocampus and cortex of AD mice was ameliorated by OCN. Besides, OCN improved the neural network function of the brain, mainly in the enhanced power of high gamma band in the medial prefrontal cortex of AD mice. The proliferation of astrocytes in the hippocampus in AD mice was also inhibited by OCN as demonstrated by immunofluorescence. Furthermore, OCN enhanced glycolysis in astrocytes and microglia, as evidenced by elevated glucose consumption, lactate production, and increased extracellular acidification rate. Such an effect was abolished when the receptor of OCN – Gpr158 was knockdown in astrocytes. Our study revealed OCN as a novel therapeutic factor for AD potentially through reducing Aβ burden and upregulation of glycolysis in neuroglia.

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Low serum levels of bone turnover markers are associated with the presence and severity of diabetic retinopathy in patients with type 2 diabetes mellitus

Cited by 15 publications

References 51 publications

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study

Osteocalcin ameliorates cognitive dysfunctions in a mouse model of Alzheimer’s Disease by reducing amyloid β burden and upregulating glycolysis in neuroglia

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