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Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence

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Abstract

Serum total osteocalcin, a marker of bone formation, may regulate glucose metabolism and influence the risk of developing adverse metabolic outcomes. We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes [e.g., metabolic syndrome (MetS)]. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, and reference lists of relevant studies to May 2015. Mean differences and risk estimates (odds ratios or relative risks) with 95 % CIs were aggregated using random-effects models. Fifty-two observational (38 cross-sectional, eight cohort, five case–control, and one both cross-sectional and cohort) studies with data on 46,998 non-overlapping participants were included. Baseline serum total osteocalcin levels were significantly lower in type 2 diabetes compared with non-type 2 diabetes and in MetS compared with non-MetS in pooled analysis of cross-sectional evidence. Pooled risk estimates (95 % CIs) for type 2 diabetes in a comparison of extreme fourths of total osteocalcin levels were 0.23 (95 % CI 0.12, 0.46) and 0.89 (95 % CI 0.78, 1.01) for cross-sectional and cohort studies respectively. The corresponding estimate was 0.39 (0.27, 0.56) for MetS from cross-sectional evidence. In both cross-sectional and cohort studies, a unit increase in serum total osteocalcin levels was associated with a significant mean increase in HOMA-B and mean reduction in HbA1c; with significant mean reductions in fasting plasma glucose levels, HOMA-IR, and body mass index in only cross-sectional studies. Available evidence—mainly from cross-sectional studies, supports inverse associations of serum total osteocalcin with risk of adverse metabolic outcomes. Large-scale prospective studies are needed to establish whether serum total osteocalcin may be useful in the prevention of adverse metabolic outcomes such as type 2 diabetes.

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Acknowledgments

We thank Anil Baran Choudhury, PhD, Government Medical college Rajnandgaon, India; Rebeca Reyes, MD, PhD, Bone Metabolic Unit (RETICEF), Endocrinology Division, Hospital Universitario San Cecilio, Av. Dr. Oloriz 16, 18012 Granada, Spain; Weiping Jia, Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shangai, China; Dong Hyun Sinn, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; and Zhen-lin Zhang, Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China for readily providing data on request.

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Authors and Affiliations

  1. Musculoskeletal Research Unit, School of Clinical Sciences, Learning and Research Building (Level 1), Southmead Hospital, University of Bristol, Southmead Road, Bristol, BS10 5NB, UK

    Setor Kwadzo Kunutsor

  2. Faculty of Health and Social Sciences, School of Health and Wellbeing, Leeds Beckett University, Room CL413, Calverley Building, Leeds, LS1 3HE, UK

    Tanefa Antoinette Apekey

  3. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland

    Jari Antero Laukkanen

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Correspondence to Setor Kwadzo Kunutsor.

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Kunutsor, S.K., Apekey, T.A. & Laukkanen, J.A. Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence. Eur J Epidemiol 30, 599–614 (2015). https://doi.org/10.1007/s10654-015-0058-x

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