title: Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence.
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.
authors.affiliation: Musculoskeletal Research Unit, School of Clinical Sciences, Learning and Research Building (Level 1), Southmead Hospital, University of Bristol, Southmead Road, Bristol, BS10 5NB, UK. skk31@cantab.net.
authors.forename: Setor Kwadzo
authors.initials: SK
authors.lastname: Kunutsor
authors.affiliation: Faculty of Health and Social Sciences, School of Health and Wellbeing, Leeds Beckett University, Room CL413, Calverley Building, Leeds, LS1 3HE, UK.
authors.forename: Tanefa Antoinette
authors.initials: TA
authors.lastname: Apekey
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland.
authors.forename: Jari Antero
authors.initials: JA
authors.lastname: Laukkanen
mesh_terms: D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D024821:Metabolic Syndrome / Q000097:blood*; D015675:Osteocalcin / Q000097:blood*; D010641:Phenotype
chemical_list: D006442:Glycated Hemoglobin; D015675:Osteocalcin
keywords: Intermediate metabolic phenotypes; Total osteocalcin; Type 2 diabetes