Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus.
Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus.
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DOI：
10.3389/fendo.2022.936159
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
众所周知，2 型糖尿病 (T2DM) 与骨密度正常有关，但同时骨转换率低且骨折风险增加。所提出的机制之一是骨前体细胞可能发生紊乱，这可以表现为循环成骨祖细胞（COP）和破骨细胞前体细胞（OCP）的缺陷。我们研究的目的是了解血糖控制程度是否对这些细胞有影响，并确定其他可能的因素。这是对美国德克萨斯州休斯顿 Michael E. DeBakey VA 医疗中心正在进行的一项临床试验中 51 名 37-65 岁男性参与者的基线数据进行的二次分析。在研究开始时，通过高效液相色谱法测量骨钙素 (OCN) 测定血清血红蛋白 A1c，通过 ELISA 测定 1 型胶原 C 末端肽 (CTx)，通过液相色谱/质谱法测定睾酮和雌二醇。通过双能X射线骨密度测定法测量面积骨矿物质密度（BMD）、骨小梁评分和身体成分，通过流式细胞术测量COP和OCP。当调整血清睾酮、甲状旁腺激素和 25-羟基维生素 D 后，长期血糖控制不佳的人 COP 百分比显着较高 (p = 0.04)。 COP 与内脏脂肪组织 (VAT) 体积呈正相关（r = 0.37，p = 0.01），与游离睾酮（r = -0.28，p = 0.05）和 OCN（r = -0.28，p = 0.07）呈负相关，尽管后者仅处于临界状态。 OCP 与年龄、FSH、腰椎 BMD 和 COP 水平呈正相关，与葡萄糖、甘油三酯和游离雌二醇呈负相关。多变量回归分析显示，除了相互预测之外，COP 的另一个独立预测因素是增值税体积，而年龄、血糖和维生素 D 是 OCP 的预测因素。我们的结果表明，高 COP 可能是代谢控制不佳的标志。然而，考虑到影响成骨细胞生成/脂肪生成的因素的复杂性和众多因素，COP 的增加可能是骨髓对血糖控制不良导致的成骨细胞凋亡增加的生理反应。或者，代谢不健康的情况也可能会阻碍成骨前体细胞向完全成熟的成骨细胞的发育。
Type 2 diabetes mellitus (T2DM) is well-known to be associated with normal bone density but, concurrently, low bone turnover and increased risk for fracture. One of the proposed mechanisms is possible derangement in bone precursor cells, which could be represented by deficiencies in circulating osteogenic progenitor (COP) cells and osteoclast precursors (OCP). The objective of our study is to understand whether extent of glycemic control has an impact on these cells, and to identify other factors that may as well. This was a secondary analysis of baseline data from 51 male participants, aged 37-65 in an ongoing clinical trial at Michael E. DeBakey VA Medical Center, Houston, Texas, USA. At study entry serum Hemoglobin A1c was measured by high-performance liquid chromatography osteocalcin (OCN) and C-terminal telopeptide of type 1 collagen (CTx) were measured by ELISA, and testosterone and estradiol by liquid-chromatography/mass-spectrometry. Areal bone mineral density (BMD), trabecular bone score and body composition were measured by dual energy x-ray absorptiometry, while COP and OCP were measured by flow cytometry. When adjusted for serum testosterone, parathyroid hormone, and 25-hydroxyvitamin D, those with poor long-term glycemic control had significantly higher percentage of COP (p = 0.04). COP correlated positively with visceral adipose tissue (VAT) volume (r = 0.37, p = 0.01) and negatively with free testosterone (r = -0.28, p = 0.05) and OCN (r = -0.28, p = 0.07), although only borderline for the latter. OCP correlated positively with age, FSH, lumbar spine BMD, and COP levels, and negatively with glucose, triglycerides, and free estradiol. Multivariable regression analyses revealed that, in addition to being predictors for each other, another independent predictor for COP was VAT volume while age, glucose, and vitamin D for OCP. Our results suggest that high COP could be a marker of poor metabolic control. However, given the complex nature and the multitude of factors influencing osteoblastogenesis/adipogenesis, it is possible that the increase in COP is a physiologic response of the bone marrow to increased osteoblast apoptosis from poor glycemic control. Alternatively, it is also likely that a metabolically unhealthy profile may retard the development of osteogenic precursors to fully mature osteoblastic cells.
影响因子：
1.5
作者：
Russo V;Colleluori G;Chen R;Mediwala S;Qualls C;Liebschner M;Villareal DT;Armamento-Villareal R
通讯作者：
Armamento-Villareal R
影响因子：
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作者：
Sowers, MaryFran R.;Randolph, John, Jr.;Jannausch, Mary;Lasley, Bill;Jackson, Elizabeth;McConnell, Daniel
通讯作者：
McConnell, Daniel