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

Abstract

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.

Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target

“…Many studies suggest that due to chronic hyperglycemia, the formation of ROS may be associated with collagen glycation, which is an important factor [4,5]. Overall, bone damage in T2DM can be caused by multiple mechanisms: accumulation of advanced glycation end products (AGEs) [79], increased levels of pro-inflammatory cytokines (e.g., IL-6, TNF-α) [80], sclerostin [81], leptin [80], lower levels of OC [11,82]), procollagen I N-terminal propeptide (P1NP) [83,84], parathyroid hormone (PTH) [85], and impairment of osteoblastogenesis [86]. The status of low bone turnover in T2DM is also reflected in lower levels of bone resorption markers (e.g., TRAP5b and C-telopeptide of type I collagen (CTx)) [82,85].…”

The complex pathophysiology of bone fragility in obesity and type 2 diabetes mellitus: therapeutic targets to promote osteogenesis

“…Furthermore, Jain et al.,studies confirmed that visceral adipose tissue (VAT) is negatively associated with bone mineral density ( 23 ). On the other hand, in T2D BMD is normal or above normal,likely protective against vertebral fractures ( 24 ), but some studies show reduced BMD ( 25 , 26 ) due to accumulation of advanced glycation end products (AGEs) ( 27 , 28 ) increased proinflammatory cytokines such as TNF-a, IL-6 ( 28 , 29 ) high sclerostin levels ( 30 ) leading to reduction in bone formation, OCN ( 31 ) and (Procollagen I N-terminal propeptide) P1NP levels in T2DM ( 31 , 32 ) and impairment in osteoblastogenesis ( 33 – 35 ). There is also reduction in bone resorption markers (CTX and TRAP5b) ( 28 ) though bone turnover markers are not as predictive of fractures compared to BMD and maybe difficult to interpret,.…”