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

Yilin Hou,1,2 Xiaoyu Hou,1,2 Qian Nie,3 Qiuyang Xia,1,2 Rui Hu,1,2 Xiaoyue Yang,1,2 Guangyao Song,2,4 Luping Ren2,4 1Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 3Health Examination Center, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 4Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Guangyao Song; Luping Ren, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email sguangyao2@163.com; renluping1122@163.comPurpose: 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 sub-classified 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 [O, p < 0.001] and increased serum P1NP levels , 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.Keywords: bone turnover markers, type 2 diabetes mellitus, microvascular complications