γ-Carboxylation of osteocalcin and insulin resistance in older men and women
γ-Carboxylation of osteocalcin and insulin resistance in older men and women
复制标题
DOI：
10.3945/ajcn.2009.28151
复制
发表时间：
2009-11-01
影响因子：
7.1
通讯作者：
Booth, Sarah L.
中科院分区：
文献类型：
--
作者：
Shea, M. Kyla;Gundberg, Caren M.;Booth, Sarah L.
背景：骨骼蛋白骨钙素被维生素K γ-羧化。高血清未羧基化骨钙素反映低维生素K状态。体外和动物研究表明，高未羧基化骨钙素与降低胰岛素抵抗有关。然而，骨钙素和胰岛素抵抗指标之间的联系尚不清楚。目的：我们的目的是研究骨钙素循环形式之间的横向和纵向联系（总的、未羧化的和羧化的）和老年男性和女性的胰岛素抵抗。设计：血清总骨钙素、羧化骨钙素用胰岛素抵抗稳态模型（HOMA-IR）测定了348例非糖尿病男性和女性（平均年龄：68岁，58%为女性）的非羧基骨钙素和胰岛素抵抗。每种形式的骨钙素在基线和3年的HOMA-IR变化之间的关联进行了检查，在162名成年人（平均年龄：69岁; 63%的女性）谁没有收到维生素Ksupplementation.Results：较低的循环未羧基化骨钙素与较高的HOMA-IR在基线或3年随访。基线时总骨钙素和羧化骨钙素最低三分位数的患者基线HOMA-IR较高（分别为P = 0.006和P = 0.02）。基线时的羧基化骨钙素浓度与HOMA-IR的3年变化呈负相关（P = 0.002）。结论：在老年人中，循环中的非羧基化骨钙素与胰岛素抵抗无关。相比之下，羧基化骨钙素和总骨钙素升高与较低的胰岛素抵抗相关，这支持了人类骨骼生理学和胰岛素抵抗之间的潜在联系。维生素K状态在这种关联中的作用尚不清楚，值得进一步研究。本试验在clinicaltrials.gov上注册为NCT 00183001。美国临床营养杂志2009; 90：1230-5.
Background: The skeletal protein osteocalcin is gamma-carboxylated by vitamin K. High serum uncarboxylated osteocalcin reflects low vitamin K status. In vitro and animal studies indicate that high uncarboxylated osteocalcin is associated with reduced insulin resistance. However, associations between osteocalcin and measures of insulin resistance in humans are less clear.Objective: Our aim was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin (total, uncarboxylated, and carboxylated) and insulin resistance in older men and women.Design: Cross-sectional associations between serum measures of total osteocalcin, carboxylated osteocalcin, and uncarboxylated osteocalcin and insulin resistance were examined in 348 nondiabetic men and women (mean age: 68 y; 58% female) by using the homeostasis model assessment of insulin resistance (HOMA-IR). Associations between each form of osteocalcin at baseline and 3-y change in HOMA-IR were examined in 162 adults (mean age: 69 y; 63% female) who did not receive vitamin K supplementation.Results: Lower circulating uncarboxylated osteocalcin was not associated with higher HOMA-IR at baseline or at 3-y follow-up. Those in the lowest tertiles of total osteocalcin and carboxylated osteocalcin at baseline had higher baseline HOMA-IR (P = 0.006 and P = 0.02, respectively). The concentration of carboxylated osteocalcin at baseline was inversely associated with a 3-y change in HOMA-IR (P = 0.002).Conclusions: In older adults, circulating uncarboxylated osteocalcin was not associated with insulin resistance. In contrast, elevated carboxylated osteocalcin and total osteocalcin were associated with lower insulin resistance, which supports a potential link between skeletal physiology and insulin resistance in humans. The role of vitamin K status in this association remains unclear and merits further investigation. This trial is registered at clinicaltrials.gov as NCT00183001. Am J Clin Nutr 2009; 90: 1230-5.