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Bone markers and cardiovascular risk in type 2 diabetes patients.

ABSTRACT: BACKGROUND:Vascular calcifications are associated with a three- to fourfold increased risk of cardiovascular disease (CVD) and are highly prevalent in type 2 diabetes patients. Emerging evidence indicates that vascular calcification is a process of active bone formation regulated by stimulators and inhibitors of calcification. Therefore, this study aimed to evaluate whether six bone markers are associated with CVD risk in patients with type 2 diabetes. METHODS:We used data of a case-cohort study, nested in the EPIC-NL cohort, comprising 134 CVD cases and a random subcohort of 218 participants, all with type 2 diabetes at baseline. Six bone markers (osteocalcin, osteopontin, osteonectin, osteoprotegerin, alkaline phosphatase and sclerostin) were measured in baseline plasma samples with multiplex assays and information on CVD events was obtained. The association of bone makers with CVD risk was evaluated using Cox proportional hazard analyses. RESULTS:Higher concentrations of plasma osteopontin were associated (ptrend?

SUBMITTER: Zwakenberg SR

PROVIDER: S-EPMC5866514 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Bone markers and cardiovascular risk in type 2 diabetes patients.

Zwakenberg Sabine R SR van der Schouw Yvonne T YT Schalkwijk Casper G CG Spijkerman Annemieke M W AMW Beulens Joline W J JWJ

Cardiovascular diabetology 20180323 1

<h4>Background</h4>Vascular calcifications are associated with a three- to fourfold increased risk of cardiovascular disease (CVD) and are highly prevalent in type 2 diabetes patients. Emerging evidence indicates that vascular calcification is a process of active bone formation regulated by stimulators and inhibitors of calcification. Therefore, this study aimed to evaluate whether six bone markers are associated with CVD risk in patients with type 2 diabetes.<h4>Methods</h4>We used data of a ca ...[more]

PMID: 29571288

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Project description:BackgroundDNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design.MethodsThe participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively.ResultsIn the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation.ConclusionsIn this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients.

Project description:Accumulating evidence has supported an increased risk of osteoporotic fracture in postmenopausal women and elderly men diagnosed with diabetes mellitus. However, it is not uncommon for young and middle-aged male patients diagnosed with type 2 diabetes mellitus (T2DM) to suffer from osteopenia or osteoporosis. Few studies focused on this population group are available. The aim of this study is to evaluate bone metabolic status and investigate the influence of T2DM on bone metabolism in 30-50-year-old men. Anthropometric assessment and blood samples were obtained from 160 patients with T2DM and 69 nondiabetic volunteers. Serum parathyroid hormone (PTH) and bone turnover markers (BTMs), including serum procollagen type I N-terminal peptide (PINP), osteocalcin (OC), and β-cross-linked C-telopeptide of type I collagen (β-CTX), were analysed. No significant differences were observed based on age, body mass index, systolic blood pressure, serum calcium, phosphorus, creatinine, total protein, and albumin levels when comparing T2DM and control groups. Fasting blood glucose, HbA1c, triglyceride (TG), total cholesterol, and low-density lipoprotein cholesterol were significantly increased, while high-density lipoprotein cholesterol was significantly decreased in the T2DM group. Compared with controls, diabetic patients showed lower serum PINP, OC, and PTH levels, whereas serum β-CTX levels were similar between the two groups. Moreover, HbA1c levels were positively correlated with PINP and inversely associated with PTH levels. TG levels were negatively correlated with OC or β-CTX levels. Furthermore, multiple linear regression revealed a positive correlation between HbA1c and PINP levels. These results also revealed a negative association between HbA1c and PTH, and between TG and OC levels, even after adjusting for expected confounder factors. Collectively, these findings indicated that young and middle-aged male patients with T2DM showed a lower turnover state resulting from bone formation inhibition. Glucose and lipid metabolic disorders may affect bone formation through different pathways.

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Bone markers and cardiovascular risk in type 2 diabetes patients.

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Bone markers and cardiovascular risk in type 2 diabetes patients.

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