Zwakenberg Sabine R, Gundberg Caren M, Spijkerman Annemieke M W, van der A Daphne L, van der Schouw Yvonne T, Beulens Joline W J
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Orthopaedics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
PLoS One. 2015 Sep 29;10(9):e0138693. doi: 10.1371/journal.pone.0138693. eCollection 2015.
To investigate whether total osteocalcin (tOC), uncarboxylated osteocalcin (ucOC) and percentage of uncarboxylated osteocalcin (%ucOC) are associated with the risk of type 2 diabetes.
This nested case control study included 1,635 participants, 833 incident diabetes cases and 802 non-diabetic control participants, aged 21-70 years from the EPIC-NL cohort. Baseline concentrations of tOC, ucOC and %ucOC were assessed. During 10 years of follow-up, diabetes cases were self-reported and verified against information from general practitioners or pharmacists. The association between the different forms of osteocalcin and diabetes risk was assessed with logistic regression adjusted for diabetes risk factors (waist circumference, age, sex, cohort, smoking status, family history of diabetes, hypertension, alcohol intake, physical activity and education) and dietary factors (total energy intake and energy adjusted intake of fat, fiber, protein and calcium).
TOC concentration was not associated with diabetes risk, with an odds ratio (OR) of 0.97 (0.91-1.03) for each ng/ml increment after adjustment for diabetes risk factors and dietary factors. No association between ucOC and %ucOC and the risk of diabetes was observed either. In sex stratified analyses (P interaction = 0.07), higher %ucOC tended to be associated with an increased risk of type 2 diabetes in a multivariable model in women (OR 1.05 for each increment of 5% ucOC (1.00-1.11), Ptrend = 0.08), but not in men (OR 0.96 for each increment of 5% ucOC (0.88-1.04)). When waist circumference was replaced by body mass index, none of the osteocalcin forms were associated with the risk of type 2 diabetes in the final model among both women and men.
Available evidence suggests that tOC, ucOC and %ucOC are each not associated with the risk of type 2 diabetes. However, more large-scale cohort studies are needed to clarify the presence of any association between the different forms of osteocalcin and the risk of type 2 diabetes.
研究总骨钙素（tOC）、未羧化骨钙素（ucOC）及未羧化骨钙素百分比（%ucOC）是否与2型糖尿病风险相关。
这项巢式病例对照研究纳入了来自EPIC-NL队列的1635名参与者，年龄在21至70岁之间，其中有833例新发糖尿病病例和802名非糖尿病对照参与者。评估了tOC、ucOC和%ucOC的基线浓度。在10年的随访期间，糖尿病病例通过自我报告，并与全科医生或药剂师提供的信息进行核对。采用逻辑回归分析不同形式骨钙素与糖尿病风险之间的关联，并对糖尿病风险因素（腰围、年龄、性别、队列、吸烟状况、糖尿病家族史、高血压、饮酒量、身体活动和教育程度）及饮食因素（总能量摄入以及脂肪、纤维、蛋白质和钙的能量校正摄入量）进行了校正。
校正糖尿病风险因素和饮食因素后，每增加1 ng/ml的tOC浓度，其与糖尿病风险的比值比（OR）为0.97（0.91 - 1.03），即tOC浓度与糖尿病风险无关。ucOC和%ucOC与糖尿病风险之间也未观察到关联。在按性别分层分析中（P交互作用 = 0.07），在多变量模型中，较高的%ucOC在女性中往往与2型糖尿病风险增加相关（每增加5% ucOC，OR为1.05（1.00 - 1.11），P趋势 = 0.08）），但在男性中并非如此（每增加5% ucOC，OR为0.96（0.88 - 1.04））。当用体重指数替代腰围时，在最终模型中，无论男性还是女性，任何一种骨钙素形式均与2型糖尿病风险无关。
现有证据表明，tOC、ucOC和%ucOC各自均与2型糖尿病风险无关。然而，需要更多大规模队列研究来阐明不同形式骨钙素与2型糖尿病风险之间是否存在关联。
