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Initial and Dynamic Risk Stratification of Pediatric Patients With Differentiated Thyroid Cancer 分化型甲状腺癌患儿的初始和动态风险分层
Pub Date : 2016-11-03 DOI: 10.1210/jc.2016-2666
Tae-Yon Sung, M. Jeon, Y. Lee, Y. Lee, Hyemi Kwon, J. Yoon, K. Chung, Won Gu Kim, D. Song, S. Hong
BackgroundThe objective of this study was to evaluate the usefulness of American Thyroid Association (ATA) risk classification and dynamic risk stratification (DRS) based on the response to initial therapy in pediatric patients with differentiated thyroid cancer (DTC).MethodsThis historical cohort study included 77 pediatric patients with DTC who underwent thyroid surgery. Clinical outcomes during median 5.3 years of follow up were assessed according to 3 ATA risk groups and 4 DRS groups.ResultsIn ATA risk classification, 22%, 48%, and 30% of patients were in the low-, intermediate-, and high-risk groups, respectively. There was no significant difference in disease-free survival (DFS) between the indeterminate and the low-risk group. The risk of recurrent/persistent disease was significantly higher only in the high risk group [hazard ratio (HR), 18.4; P = 0.005]. In DRS, 49%, 13%, 6%, and 31% of patients were classified in the excellent, indeterminate, biochemical incomplete, and structural incomplete response groups, respectively. The risk of recurrent/persistent disease was significantly higher in the indeterminate group (HR, 10.2; P = 0.045) and in the structural incomplete group (HR, 98.7; P = 0.005) compared with the excellent response group.ConclusionsDRS based on the response to initial therapy could be useful in addition to initial ATA pediatric risk classification to predict recurrent/persistent disease in pediatric patients with DTC.
本研究的目的是评估美国甲状腺协会(ATA)风险分类和动态风险分层(DRS)基于初始治疗对分化型甲状腺癌(DTC)患儿的疗效。方法本研究纳入77例行甲状腺手术的小儿DTC患者。根据3个ATA风险组和4个DRS组评估中位5.3年随访期间的临床结果。结果在ATA风险分类中,低危、中危、高危组分别占22%、48%和30%。不确定组和低危组无病生存期(DFS)无显著差异。只有高危组复发/持续性疾病的风险显著高于高危组[危险比(HR), 18.4;P = 0.005]。在DRS中,49%、13%、6%和31%的患者分别被分为极好、不确定、生化不完全和结构不完全缓解组。不确定组复发/持续性疾病的风险明显更高(HR, 10.2;P = 0.045),结构不完整组(HR, 98.7;P = 0.005)。结论基于初始治疗反应的sdrs可用于预测DTC患儿的复发/持续性疾病。
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引用次数: 25
Liver Fat and Insulin Sensitivity Define Metabolite Profiles During a Glucose Tolerance Test in Young Adult Twins 肝脏脂肪和胰岛素敏感性在年轻成年双胞胎糖耐量试验中定义代谢物谱
Pub Date : 2016-11-03 DOI: 10.1210/jc.2015-3512
Joel T. Rämö, Sanna M. Kaye, S. Jukarainen, L. Bogl, A. Hakkarainen, J. Lundbom, N. Lundbom, A. Rissanen, J. Kaprio, N. Matikainen, K. Pietiläinen
ContextThe associations of body mass index (BMI) and liver fat (LF) with circulating prandial metabolomic markers are incompletely understood.ObjectiveWe aimed to characterize circulating metabolite excursions during an oral glucose tolerance test (OGTT) and evaluate whether the metabolomic signatures of BMI discordance coassociate with LF content.Design, Setting, and ParticipantsWe measured 80 metabolite parameters by nuclear magnetic resonance, together with glucose and insulin, during a 2-hour OGTT in 64 monozygotic (MZ) and 73 dizygotic (DZ) twin pairs (aged 22.8 to 36.2 years). Metabolite excursions during the OGTT were compared within BMI-discordant (intrapair difference, BMI ≥ 3 kg/m2) cotwins separately within MZ and DZ pairs. Insulin-based indices were calculated from the OGTT. LF was measured by magnetic resonance spectroscopy in 25 BMI-discordant MZ pairs. Metabolite profiles were compared with respect to LF discordance (ΔLF% ≥ 2%).ResultsWe replicated many previously reported OGTT-induced metabolite excursions in all 274 individuals and report novel lipoprotein excursions. The associations between some metabolite excursions and BMI differed in MZ and DZ twins. In BMI-discordant MZ pairs (mean ΔBMI = 4.9 kg/m2) who were concordant for LF (Δ0.2%), few metabolites differed between the cotwins: very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B were elevated, and high-density lipoprotein size and concentration were decreased in the cotwins with higher BMI. In contrast, in BMI-discordant MZ pairs (ΔBMI = 6.1 kg/m2) who were discordant for LF (Δ6.8%), cotwins with higher BMI exhibited lower insulin sensitivity and widespread metabolomic differences: elevations in small VLDL and low-density lipoprotein particles, fatty acids (FAs), and isoleucine. Within all 64 MZ twin pairs, lower insulin sensitivity associated with higher levels of VLDLs, triglycerides, FAs, and isoleucine.ConclusionsBMI-discordant MZ twin pairs who also are discordant for LF have more pronounced within-pair differences in metabolomics profiles during an OGTT than BMI-discordant pairs without LF discordance.
身体质量指数(BMI)和肝脏脂肪(LF)与循环膳食代谢组学标志物的关系尚不完全清楚。目的:研究口服糖耐量试验(OGTT)中循环代谢物漂移的特征,并评估BMI不一致的代谢组学特征是否与LF含量相关。设计、设置和参与者:在2小时OGTT期间,我们通过核磁共振测量了64对单卵(MZ)和73对异卵(DZ)双胞胎(年龄22.8至36.2岁)的80种代谢物参数,以及葡萄糖和胰岛素。分别比较MZ和DZ对中BMI不一致(对内差异,BMI≥3kg /m2)的双胞胎在OGTT期间的代谢物漂移。基于胰岛素的指数由OGTT计算。用磁共振波谱法测定25个bmi -不一致MZ对的LF。比较LF不一致的代谢物谱(ΔLF%≥2%)。结果我们在所有274个人中重复了许多先前报道的ogtt诱导的代谢物漂移,并报告了新的脂蛋白漂移。在MZ和DZ双胞胎中,一些代谢物漂移与BMI之间的关系有所不同。在BMI不一致的MZ对(平均ΔBMI = 4.9 kg/m2)中,与LF (Δ0.2%)一致的双胞胎之间代谢物几乎没有差异:BMI较高的双胞胎中,极低密度脂蛋白(VLDL)胆固醇和载脂蛋白B升高,高密度脂蛋白的大小和浓度降低。相反,BMI不一致的MZ对(ΔBMI = 6.1 kg/m2)与LF不一致(Δ6.8%), BMI较高的双胞胎表现出较低的胰岛素敏感性和广泛的代谢组学差异:小VLDL和低密度脂蛋白颗粒、脂肪酸(FAs)和异亮氨酸升高。在所有64对MZ双胞胎中,较低的胰岛素敏感性与较高的vldl、甘油三酯、FAs和异亮氨酸水平相关。结论bmi -不一致的MZ双胞胎在OGTT中代谢组学谱的差异比bmi -不一致的MZ双胞胎更明显。
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引用次数: 15
Presence of Autoreactive, MHC Class I–Restricted, Calcium-Sensing Receptor (CaSR)–Specific CD8+ T Cells in Idiopathic Hypoparathyroidism 在特发性甲状旁腺功能减退症中存在自体反应性、MHC i类限制性、钙敏感受体(CaSR)特异性CD8+ T细胞
Pub Date : 2016-11-02 DOI: 10.1210/jc.2016-3131
Samrina Mahtab, U. Vaish, S. Saha, Archana Singh, R. Goswami, R. Rani
ContextMajor histocompatibility complex class I allele HLA-A*26:01 and human leukocyte antigen (HLA) supertype A01 (STA01) are increased in idiopathic hypoparathyroidism (IH). However, cell-mediated autoimmune responses directed against the calcium-sensing receptor (CaSR) have not been demonstrated.ObjectiveTo study CaSR-specific cytotoxic T-cell responses in peripheral blood mononuclear cells of IH patients.DesignTwenty-four peptides of CaSR (RH1 to RH24) were evaluated for their ex vivo potential to stimulate PBMCs from IH patients and controls in interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assays.SettingTertiary patient care center and National Institute of Immunology, New Delhi, India.Patients and Other ParticipantsForty-five patients with IH attending the endocrine clinic of the All India Institute of Medical Sciences and 22 healthy controls.Main Outcome MeasuresMajor histocompatibility complex class-I restricted, CaSR-specific cytotoxic CD8+ T-cell responses evaluated by IFN-γ ELISPOT assay.ResultsOf IH patients, 82.2% showed IFN-γ-secreting cells when stimulated ex-vivo with CaSR peptides. Peptides RH7, RH9, and RH16 elicited HLA supertype A01-restricted responses in IH. RH8, RH14, RH15, RH20, and RH21 peptides induced significantly higher responses in STA01+ IH patients compared with healthy controls irrespective of their supertype A01 status.ConclusionsOur ex vivo IFN-γ ELISPOT assays demonstrate the presence of CaSR-specific memory CD8+ T cells in the peripheral circulation of patients with IH, suggesting the role of cell-mediated autoimmune responses in the etiopathogenesis of IH.
主要组织相容性复合体I类等位基因HLA- a *26:01和人白细胞抗原(HLA)超型A01 (STA01)在特发性甲状旁腺功能减退症(IH)中升高。然而,针对钙敏感受体(CaSR)的细胞介导的自身免疫反应尚未得到证实。目的研究IH患者外周血单个核细胞对casr特异性细胞毒t细胞的反应。设计采用干扰素(IFN)-γ酶联免疫斑点法(ELISPOT)检测了24种CaSR肽(RH1至RH24)在体外刺激IH患者和对照组PBMCs的潜力。三级病人护理中心和国家免疫研究所,印度新德里。患者和其他参与者:45名在全印度医学科学研究所内分泌诊所就诊的IH患者和22名健康对照者。主要观察指标:主要组织相容性复合体i类限制性,casr特异性细胞毒性CD8+ t细胞反应通过IFN-γ ELISPOT测定。结果体外CaSR肽刺激IH患者,82.2%出现IFN-γ分泌细胞。多肽RH7、RH9和RH16在IH中引发HLA超型a01限制性反应。与健康对照者相比,与STA01+ IH患者的超型A01状态无关,RH8、RH14、RH15、RH20和RH21肽诱导的应答明显更高。结论体外IFN-γ ELISPOT检测证实IH患者外周血中存在casr特异性记忆性CD8+ T细胞,提示细胞介导的自身免疫反应在IH发病机制中的作用。
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引用次数: 8
Preservation of Reduced Numbers of Insulin-Positive Cells in Sulfonylurea-Unresponsive KCNJ11-Related Diabetes 磺脲无反应的kcnj11相关糖尿病中胰岛素阳性细胞数量减少的保存
Pub Date : 2016-11-01 DOI: 10.1210/jc.2016-2826
S. Greeley, Mark C. Zielinski, A. Poudel, Honggang Ye, Shivani Berry, J. Taxy, D. Carmody, D. Steiner, L. Philipson, Jamie Wood, M. Hara
ContextThe most common genetic cause of permanent neonatal diabetes mellitus is activating mutations in KCNJ11, which can usually be treated using oral sulfonylureas (SUs) instead of insulin injections, although some mutations are SU unresponsive. In this work, we provide a report of the pancreatic islet endocrine cell composition and area in a patient with an SU-unresponsive KCNJ11 mutation (p.G334D), in comparison with age-matched controls.Case DescriptionPancreatic autopsy tissue sections from a 2-year-old female child diagnosed with KCNJ11-related diabetes at 4 days of age and 13 age-matched controls were stained with insulin, glucagon, somatostatin, pancreatic polypeptide, and Ki67 antibodies to determine islet endocrine cell composition and area. β-cell ultrastructure was assessed by electron microscopic (EM) analysis. The patient's pancreas (sampling from head to tail) revealed insulin-positive cells in all regions. The pancreatic β-cell (insulin) area was significantly reduced compared with controls: 0.50% ± 0.04% versus 1.67% ± 0.20%, respectively (P < 0.00001). There were no significant differences in α-cell (glucagon) or δ-cell (somatostatin) area. EM analysis revealed secretory granules with a dense core typical of mature β-cells as well as granules with a lighter core characteristic of immature granules.ConclusionsOur results suggest that mechanisms exist that allow preservation of β-cells in the absence of insulin secretion. It remains to be determined to what extent this reduction in β-cells may be reversible.
永久性新生儿糖尿病最常见的遗传原因是KCNJ11的激活突变,通常可以使用口服磺脲类药物(SUs)而不是胰岛素注射来治疗,尽管一些突变对SU没有反应。在这项工作中,我们提供了一份报告,报告了su无反应的KCNJ11突变(p.G334D)患者的胰岛内分泌细胞组成和面积,并与年龄匹配的对照组进行了比较。病例描述:对一名4日龄诊断为kcnj11相关糖尿病的2岁女童和13名年龄匹配的对照组进行胰腺解剖组织切片,用胰岛素、胰高血糖素、生长抑素、胰腺多肽和Ki67抗体进行染色,以确定胰岛内分泌细胞的组成和面积。电镜观察β细胞超微结构。患者的胰腺(从头到尾取样)在所有区域显示胰岛素阳性细胞。胰腺β细胞(胰岛素)面积与对照组相比显著减少:分别为0.50%±0.04%和1.67%±0.20% (P < 0.00001)。α-细胞(胰高血糖素)和δ-细胞(生长抑素)面积差异无统计学意义。电镜分析显示,分泌颗粒具有成熟β细胞典型的致密核心,而颗粒具有未成熟颗粒特征的较轻核心。结论在缺乏胰岛素分泌的情况下,β-细胞的保存存在一定的机制。β细胞的这种减少在多大程度上是可逆的还有待确定。
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引用次数: 30
Effects of Oxandrolone on Cardiometabolic Health in Boys With Klinefelter Syndrome: A Randomized Controlled Trial 奥雄龙对克氏综合征男孩心脏代谢健康的影响:一项随机对照试验
Pub Date : 2016-11-01 DOI: 10.1210/jc.2016-2904
S. Davis, Matthew Cox-Martin, M. Bardsley, Karen Kowal, P. Zeitler, J. Ross
ContextKlinefelter syndrome (KS) is a common condition in males, resulting in androgen deficiency and cardiometabolic diseases. These interrelated conditions may be present in prepubertal boys with KS.ObjectiveTo determine whether supplemental low-dose androgen has a beneficial effect on body composition in prepubertal boys with KS.Design, Setting, and ParticipantsWe conducted a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial in 93 boys with KS aged 4 to 12 years.InterventionsOral oxandrolone (Ox) 0.06 mg/kg/d or placebo for 2 years.Outcome MeasuresThe primary outcome was percent body fat standard deviation score (%BF SDS) at 2 years. Secondary outcomes included additional measures of cardiometabolic health and safety.ResultsThe %BF SDS at 2 years was significantly lower in the treatment (0.29 ± 0.76 SDS) compared with placebo group (0.81 ± 0.72 SDS) after adjusting for age and baseline %BF SDS (95% confidence interval for the difference between means -0.86 to -0.19 SDS, P = 0.009). Ox resulted in lower triglycerides (P = 0.043), but also lower high-density lipoprotein (HDL) cholesterol (P < 0.001) and a more rapid advancement in bone age (P = 0.011).ConclusionsOx has positive effects on measures of cardiometabolic health in prepubertal boys with KS; however, it does lower HDL cholesterol and advance bone age.
klinefelter综合征(KS)是男性的常见病,导致雄激素缺乏和心脏代谢疾病。这些相互关联的条件可能存在于青春期前患有KS的男孩中。目的探讨补充低剂量雄激素对青春期前KS男孩体成分的影响。设计、环境和参与者我们对93名4至12岁的KS男孩进行了一项随机、双盲、安慰剂对照的临床试验进行了二次分析。介入治疗:口服奥雄龙(Ox) 0.06 mg/kg/d或安慰剂2年。主要终点是2年时体脂百分率标准偏差评分(%BF SDS)。次要结果包括额外的心脏代谢健康和安全性测量。结果经年龄和基线%BF SDS调整后,治疗组2年时BF SDS %(0.29±0.76 SDS)显著低于安慰剂组(0.81±0.72 SDS)(95%可信区间均值-0.86 ~ -0.19 SDS, P = 0.009)。牛导致甘油三酯降低(P = 0.043),高密度脂蛋白(HDL)胆固醇降低(P < 0.001),骨龄加快(P = 0.011)。结论sox对青春期前KS男孩心脏代谢健康指标有积极影响;然而,它确实能降低高密度脂蛋白胆固醇并促进骨龄。
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引用次数: 29
Sex Differences in Associations of Adiposity Measures and Insulin Resistance in US Hispanic/Latino Youth: The Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth) 美国西班牙裔/拉丁裔青年肥胖测量和胰岛素抵抗相关性的性别差异:西班牙裔社区儿童健康研究/拉丁裔青年研究(SOL Youth)
Pub Date : 2016-11-01 DOI: 10.1210/jc.2016-2279
Q. Qi, S. Hua, K. Perreira, Jianwen Cai, L. Van Horn, N. Schneiderman, B. Thyagarajan, A. Delamater, R. Kaplan, C. Isasi
ContextUS Hispanic/Latino youth are disproportionally affected by the obesity and diabetes.ObjectiveWe examined associations of adiposity measures with insulin resistance (IR) and hyperglycemia and the influences of sex and pubertal development on these associations.Design, Setting, and ParticipantsWe performed a cross-sectional analysis of 1223 8- to 16-year-old Hispanic/Latino youth from a community-based study in the United States (SOL Youth).Main Outcome MeasuresWe measured IR (≥75th percentile of sex-specific Homeostatic Model Assessment of Insulin Resistance) and hyperglycemia (fasting glucose ≥100 mg/dL or hemoglobin a1c ≥5.7%).ResultsIn boys, body mass index (BMI) showed the strongest association with IR [prevalence ratio (PR), 2.10; 95% confidence interval (CI), 1.87 to 2.36 per standard deviation], which was not statistically different compared with body fat percentage (%BF) (PR, 2.03; 95% CI, 1.81 to 2.29) and waist circumference (WC) (PR, 1.89; 95% CI, 1.67 to 2.13) but was significantly stronger compared with fat mass index (FMI) (PR, 1.79; 95% CI, 1.63 to 1.96), waist-to-hip ratio (WHR) (PR, 1.32; 95% CI, 1.21 to 1.44), and waist-to-height ratio (WHtR) (PR, 1.76; 95% CI, 1.54 to 2.01) (P for difference, <0.05). In girls, %BF (PR, 2.73; 95% CI, 2.34 to 3.20) showed a significantly stronger association with IR compared with BMI (PR, 1.48; 95% CI, 1.29 to 1.70), FMI (PR, 1.71; 95% CI, 1.49 to 1.95), WC (PR, 1.96; 95% CI, 1.70 to 2.27), WHR (PR, 1.95; 95% CI, 1.70 to 2.23), and WHtR (PR, 1.79; 95% CI, 1.53 to 2.09) (P for difference, <0.003). Associations between adiposity measures and IR were generally stronger among children in puberty versus those who had completed puberty, with significant interactions for WC and WHtR in boys and for BMI in girls (P for interaction, <0.01). Adiposity measures were modestly associated with hyperglycemia (PR, 1.14 to 1.25), with no interactions with sex or pubertal status.ConclusionsSex and puberty may influence associations between adiposity measures and IR in US Hispanic/Latino youth. Multiple adiposity measures are needed to better assess IR risk between boys and girls according to pubertal status.
西班牙裔/拉丁裔青年受肥胖和糖尿病的影响尤为严重。目的探讨肥胖指标与胰岛素抵抗(IR)和高血糖的关系,以及性别和青春期发育对这些关系的影响。设计、环境和参与者我们对1223名来自美国社区研究(SOL youth)的8至16岁的西班牙/拉丁裔青年进行了横断面分析。我们测量了IR(胰岛素抵抗性别特异性稳态模型评估≥75百分位数)和高血糖(空腹血糖≥100 mg/dL或糖化血红蛋白≥5.7%)。结果在男孩中,体重指数(BMI)与IR的相关性最强[患病率比(PR)为2.10;95%可信区间(CI), 1.87 ~ 2.36 /标准差],与体脂率(%BF)比较无统计学差异(PR, 2.03;95% CI, 1.81 ~ 2.29)和腰围(WC) (PR, 1.89;95% CI, 1.67 ~ 2.13),但与脂肪质量指数(FMI)相比显著增强(PR, 1.79;95% CI, 1.63 ~ 1.96),腰臀比(WHR) (PR, 1.32;95% CI, 1.21 ~ 1.44),腰高比(WHtR) (PR, 1.76;95% CI, 1.54 ~ 2.01) (P为差异,<0.05)。女孩中BF % (PR, 2.73;95% CI, 2.34 ~ 3.20)与BMI相比,IR的相关性显著增强(PR, 1.48;95% CI, 1.29 ~ 1.70), FMI (PR, 1.71;95% CI, 1.49 ~ 1.95), WC (PR, 1.96;95% CI, 1.70 ~ 2.27), WHR (PR, 1.95;95% CI, 1.70 ~ 2.23)和WHtR (PR, 1.79;95% CI, 1.53 ~ 2.09) (P为差异,<0.003)。青春期儿童与已完成青春期的儿童相比,肥胖测量与IR之间的关联通常更强,男孩的WC和WHtR以及女孩的BMI之间存在显著的相互作用(相互作用P <0.01)。肥胖测量与高血糖有一定的相关性(PR, 1.14 - 1.25),与性别或青春期状态没有相互作用。结论性别和青春期可能影响美国西班牙裔/拉丁裔青年肥胖测量和IR之间的关联。根据青春期状况,需要多种肥胖测量来更好地评估男孩和女孩之间的IR风险。
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引用次数: 21
Prepubertal Impact of Protein Intake and Physical Activity on Weight-Bearing Peak Bone Mass and Strength in Males 青春期前蛋白质摄入和体力活动对男性负重峰值骨量和力量的影响
Pub Date : 2016-11-01 DOI: 10.1210/jc.2016-2449
T. Chevalley, J. Bonjour, M. Audet, F. Merminod, B. van Rietbergen, R. Rizzoli, S. Ferrari
ContextPeak bone mass (PBM) and strength are important determinants of fracture risk in later life. During growth, bone is responsive to changes in nutrition and physical activity (PA), particularly before pubertal maturation.ObjectiveIn prepubertal healthy boys, protein intake (Prot-Int) enhances the impact of PA on weight-bearing bone. We hypothesized that the synergism between Prot-Int and PA on proximal femur as recorded at 7.4 years would track until PBM.MethodsA total of 124 boys were followed from 7.4 to 15.2 and 22.6 years. At 7.4 years, they were dichotomized according to the median of both PA and Prot-Int.ResultsIn boys with PA greater than the median (310 vs 169 kcal ⋅ d-1), higher vs low Prot-Int (57.7 vs 38.0 g ⋅ d-1) was associated with +9.8% greater femoral neck (FN) bone mineral content (BMC) (P = 0.027) at 7.4 years. At 15.2 and 22.6 years, this difference was maintained: FN BMC: +12.7% (P = 0.012) and +11.3% (P = 0.016), respectively. With PA greater than the median, in Prot-Int greater than vs less than the median, differences in FN BMC z scores were +0.60, +0.70, and +0.68 at 7.4, 15.2, and 22.6 years, respectively. Microfinite element analysis of distal tibia at 15.2 and 22.6 years indicated that in the 2 groups with PA greater than the median, cross-sectional area, stiffness, and failure load were greater in Prot-Int greater than vs less than the median.ConclusionsThis study demonstrates the crucial influence of Prot-Int on the response to enhanced PA and the importance of prepubertal years for modifying the bone growth trajectory and, thereby, for achieving higher PBM and greater strength in healthy male participants.
峰值骨量(PBM)和强度是晚年骨折风险的重要决定因素。在生长过程中,骨骼对营养和身体活动(PA)的变化做出反应,特别是在青春期成熟之前。目的在青春期前健康男孩中,蛋白质摄入(Prot-Int)可增强PA对负重骨的影响。我们假设在7.4岁时记录的股骨近端Prot-Int和PA之间的协同作用将持续到PBM。方法对124例男孩进行随访,随访年龄分别为7.4 ~ 15.2岁和22.6岁。在7.4岁时,根据PA和Prot-Int的中位数进行二分类。结果PA大于中位数(310 vs 169 kcal⋅d-1)的男孩,7.4岁时,高/低Prot-Int (57.7 vs 38.0 g⋅d-1)与股骨颈(FN)骨矿物质含量(BMC)增加+9.8% (P = 0.027)相关。在15.2岁和22.6岁时,这种差异保持不变:FN BMC分别为+12.7% (P = 0.012)和+11.3% (P = 0.016)。如果PA大于中位数,Prot-Int大于或小于中位数,在7.4、15.2和22.6年时,FN BMC z评分的差异分别为+0.60、+0.70和+0.68。在15.2岁和22.6岁时对胫骨远端进行的微有限元分析表明,在PA大于中位数的两组中,Prot-Int的横截面积、刚度和破坏载荷均大于中位数和小于中位数。结论:本研究证明了Prot-Int对PA增强反应的关键影响,以及青春期前年龄对改变骨骼生长轨迹的重要性,从而在健康男性参与者中获得更高的PBM和更大的力量。
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引用次数: 13
Effect of Soy in Men With Type 2 Diabetes Mellitus and Subclinical Hypogonadism: A Randomized Controlled Study 大豆对男性2型糖尿病和亚临床性腺功能减退的影响:一项随机对照研究
Pub Date : 2016-10-31 DOI: 10.1210/jc.2016-2875
T. Sathyapalan, A. Rigby, S. Bhasin, N. Thatcher, E. Kilpatrick, S. Atkin
Context: Isoflavones found in soy products have a chemical structure similar to estrogen, leading to concerns of an adverse estrogenic effect in men, particularly in those with type 2 diabetes mellitus (T2DM) who have low testosterone levels due to hypogonadism. Objective: The primary outcome was change in total testosterone levels. The secondary outcomes were the changes in glycemia and cardiovascular risk markers. Design: This was a randomized double-blind parallel study. Setting: This study occurred in a secondary care setting in United Kingdom. Participants: Two hundred men with T2DM and a total testosterone level ⩽12 nmol/L were included. Intervention: Fifteen grams of soy protein with 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily as snack bars for 3 months were administered. Results: There was no change in either total testosterone or in absolute free testosterone levels with either SPI or SP. There was an increase in thyrotropin (TSH) and reduction in free thyroxine (fT4; P < 0.01) after SPI supplementation. Glycemic control improved with a significant reduction in hemoglobin A1c (−4.19 [7.29] mmol/mol, P < 0.01) and homeostasis model of assessment - insulin resistance after SPI. Cardiovascular risk improved with a reduction in triglycerides, C-reactive protein, and diastolic blood pressure (DBP; P < 0.05) with SPI vs SP supplementation. There was a 6% improvement in 10-year coronary heart disease risk after 3 months of SPI supplementation. Endothelial function improved with both SPI and SP supplementation (P < 0.01), with an increased reactive hyperemia index that was greater for the SPI group (P < 0.05). Conclusions: Testosterone levels were unchanged and there was a substantial improvement in glycaemia and cardiovascular risk markers with SPI compared with SP alone over 3 months. There was also a substantial increase in TSH and a reduction in fT4.
背景:豆制品中发现的异黄酮具有与雌激素相似的化学结构,这引起了人们对男性不良雌激素效应的担忧,特别是对那些因性腺功能减退而睾酮水平较低的2型糖尿病(T2DM)患者。目的:主要观察指标为总睾酮水平的变化。次要结果是血糖和心血管危险指标的变化。设计:这是一项随机双盲平行研究。环境:本研究发生在英国的二级医疗机构。参与者:纳入200名总睾酮水平≥12 nmol/L的2型糖尿病男性。干预措施:每天15克大豆蛋白含66毫克异黄酮(SPI)或15克大豆蛋白不含异黄酮(SP)作为零食棒,持续3个月。结果:SPI和SP对总睾酮和绝对游离睾酮水平均无影响,促甲状腺激素(TSH)升高,游离甲状腺素(fT4)降低;P < 0.01)。血糖控制得到改善,糖化血红蛋白(A1c)显著降低(- 4.19 [7.29]mmol/mol, P < 0.01), SPI后评估胰岛素抵抗的稳态模型显著降低。心血管风险随着甘油三酯、c反应蛋白和舒张压(DBP)的降低而改善;P < 0.05)。在补充SPI 3个月后,10年冠心病风险提高了6%。添加SPI和SP均可改善内皮功能(P < 0.01),且SPI组反应性充血指数升高(P < 0.05)。结论:在3个月的时间里,与单独使用SPI相比,睾酮水平没有变化,血糖和心血管危险指标有显著改善。TSH也大幅增加,fT4也大幅减少。
{"title":"Effect of Soy in Men With Type 2 Diabetes Mellitus and Subclinical Hypogonadism: A Randomized Controlled Study","authors":"T. Sathyapalan, A. Rigby, S. Bhasin, N. Thatcher, E. Kilpatrick, S. Atkin","doi":"10.1210/jc.2016-2875","DOIUrl":"https://doi.org/10.1210/jc.2016-2875","url":null,"abstract":"Context: Isoflavones found in soy products have a chemical structure similar to estrogen, leading to concerns of an adverse estrogenic effect in men, particularly in those with type 2 diabetes mellitus (T2DM) who have low testosterone levels due to hypogonadism. Objective: The primary outcome was change in total testosterone levels. The secondary outcomes were the changes in glycemia and cardiovascular risk markers. Design: This was a randomized double-blind parallel study. Setting: This study occurred in a secondary care setting in United Kingdom. Participants: Two hundred men with T2DM and a total testosterone level ⩽12 nmol/L were included. Intervention: Fifteen grams of soy protein with 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily as snack bars for 3 months were administered. Results: There was no change in either total testosterone or in absolute free testosterone levels with either SPI or SP. There was an increase in thyrotropin (TSH) and reduction in free thyroxine (fT4; P < 0.01) after SPI supplementation. Glycemic control improved with a significant reduction in hemoglobin A1c (−4.19 [7.29] mmol/mol, P < 0.01) and homeostasis model of assessment - insulin resistance after SPI. Cardiovascular risk improved with a reduction in triglycerides, C-reactive protein, and diastolic blood pressure (DBP; P < 0.05) with SPI vs SP supplementation. There was a 6% improvement in 10-year coronary heart disease risk after 3 months of SPI supplementation. Endothelial function improved with both SPI and SP supplementation (P < 0.01), with an increased reactive hyperemia index that was greater for the SPI group (P < 0.05). Conclusions: Testosterone levels were unchanged and there was a substantial improvement in glycaemia and cardiovascular risk markers with SPI compared with SP alone over 3 months. There was also a substantial increase in TSH and a reduction in fT4.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"120 1","pages":"425–433"},"PeriodicalIF":0.0,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76007209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 41
Low DHEAS: A Sensitive and Specific Test for the Detection of Subclinical Hypercortisolism in Adrenal Incidentalomas 低DHEAS:一种检测肾上腺偶发瘤亚临床高皮质醇症的敏感和特异性试验
Pub Date : 2016-10-31 DOI: 10.1210/jc.2016-2718
Conall Dennedy, A. Annamalai, Olivia Prankerd-Smith, Natalie Freeman, Kuhan Vengopal, J. Graggaber, O. Koulouri, A. Powlson, A. Shaw, D. Halsall
ContextSubclinical hypercortisolism (SH) occurs in 5% to 30% of adrenal incidentalomas (AIs). Common screening tests for adrenocorticotropin-independent hypercortisolism have substantial false-positive rates, mandating further time and resource-intensive investigations.ObjectiveTo determine whether low basal dehydroepiandrosterone sulfate (DHEAS) is a sensitive and specific screening test for SH in AI.Setting and PatientsIn total, 185 patients with AI were screened for adrenal medullary (plasma metanephrines) and cortical [1 mg overnight dexamethasone suppression test (ONDST), 24-hour urinary free cortisol (UFC), serum DHEAS, plasma renin, and aldosterone] hyperfunction. Positive ONDST [≥1.8 mcg/dL (≥50 nmol/L)] and/or UFC (more than the upper limit of reference range) results were further investigated. We diagnosed SH when at least 2 of the following were met: raised UFC, raised midnight serum cortisol, 48-hour dexamethasone suppression test (DST) cortisol ≥1.8 mcg/dL (≥50 nmol/L).Results29 patients (16%) were diagnosed with SH. Adrenocorticotropin was <10 pg/mL (<2.2 pmol/L) in all patients with SH. We calculated age- and sex-specific DHEAS ratios (derived by dividing the DHEAS by the lower limit of the respective reference range) for all patients. Receiver operating characteristic curve analyses demonstrated that a ratio of 1.12 was sensitive (>99%) and specific (91.9%) for the diagnosis of SH. Cortisol following 1 mg ONDST of 1.9 mcg/dL (53 nmol/L) was a sensitive (>99%) screening test for SH but had lower specificity (82.9%). The 24-hour UFC lacked sensitivity (69%) and specificity (72%).ConclusionA single basal measurement of DHEAS offers comparable sensitivity and greater specificity to the existing gold-standard 1 mg DST for the detection of SH in patients with AIs.
亚临床高皮质醇症(SH)发生在5% - 30%的肾上腺偶发瘤(AIs)中。普通的促肾上腺皮质激素非依赖性高皮质醇症的筛查试验有大量的假阳性率,需要进一步的时间和资源密集的调查。目的探讨低基础硫酸脱氢表雄酮(DHEAS)是否可作为一种敏感、特异的筛查SH的方法。共筛查185例AI患者的肾上腺髓质(血浆肾上腺素)和皮质[1 mg地塞米松夜间抑制试验(ONDST), 24小时尿游离皮质醇(UFC),血清DHEAS,血浆肾素和醛固酮]功能亢进。进一步研究ONDST[≥1.8 mcg/dL(≥50 nmol/L)]和/或UFC(超过参考范围上限)阳性结果。当至少满足以下2项时诊断为SH: UFC升高,午夜血清皮质醇升高,48小时地塞米松抑制试验(DST)皮质醇≥1.8 mcg/dL(≥50 nmol/L)。结果29例(16%)患者被诊断为SH,促肾上腺皮质激素诊断为99%,特异性诊断为91.9%。1 mg ONDST (1.9 mcg/dL (53 nmol/L))后的皮质醇是SH的敏感(>99%)筛查试验,但特异性较低(82.9%)。24小时UFC缺乏敏感性(69%)和特异性(72%)。结论单一的DHEAS基础测量方法与现有的金标准1mg DST检测AIs患者SH具有相当的灵敏度和更高的特异性。
{"title":"Low DHEAS: A Sensitive and Specific Test for the Detection of Subclinical Hypercortisolism in Adrenal Incidentalomas","authors":"Conall Dennedy, A. Annamalai, Olivia Prankerd-Smith, Natalie Freeman, Kuhan Vengopal, J. Graggaber, O. Koulouri, A. Powlson, A. Shaw, D. Halsall","doi":"10.1210/jc.2016-2718","DOIUrl":"https://doi.org/10.1210/jc.2016-2718","url":null,"abstract":"Context\u0000Subclinical hypercortisolism (SH) occurs in 5% to 30% of adrenal incidentalomas (AIs). Common screening tests for adrenocorticotropin-independent hypercortisolism have substantial false-positive rates, mandating further time and resource-intensive investigations.\u0000\u0000\u0000Objective\u0000To determine whether low basal dehydroepiandrosterone sulfate (DHEAS) is a sensitive and specific screening test for SH in AI.\u0000\u0000\u0000Setting and Patients\u0000In total, 185 patients with AI were screened for adrenal medullary (plasma metanephrines) and cortical [1 mg overnight dexamethasone suppression test (ONDST), 24-hour urinary free cortisol (UFC), serum DHEAS, plasma renin, and aldosterone] hyperfunction. Positive ONDST [≥1.8 mcg/dL (≥50 nmol/L)] and/or UFC (more than the upper limit of reference range) results were further investigated. We diagnosed SH when at least 2 of the following were met: raised UFC, raised midnight serum cortisol, 48-hour dexamethasone suppression test (DST) cortisol ≥1.8 mcg/dL (≥50 nmol/L).\u0000\u0000\u0000Results\u000029 patients (16%) were diagnosed with SH. Adrenocorticotropin was <10 pg/mL (<2.2 pmol/L) in all patients with SH. We calculated age- and sex-specific DHEAS ratios (derived by dividing the DHEAS by the lower limit of the respective reference range) for all patients. Receiver operating characteristic curve analyses demonstrated that a ratio of 1.12 was sensitive (>99%) and specific (91.9%) for the diagnosis of SH. Cortisol following 1 mg ONDST of 1.9 mcg/dL (53 nmol/L) was a sensitive (>99%) screening test for SH but had lower specificity (82.9%). The 24-hour UFC lacked sensitivity (69%) and specificity (72%).\u0000\u0000\u0000Conclusion\u0000A single basal measurement of DHEAS offers comparable sensitivity and greater specificity to the existing gold-standard 1 mg DST for the detection of SH in patients with AIs.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"13 1","pages":"786–792"},"PeriodicalIF":0.0,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79111044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 60
Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes 基线HbA1c识别高危妊娠糖尿病:早期与标准妊娠糖尿病的应用
Pub Date : 2016-10-31 DOI: 10.1210/jc.2016-2951
A. Sweeting, G. Ross, J. Hyett, L. Molyneaux, K. Tan, M. Constantino, A. Harding, J. Wong
ContextThe increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes.ObjectiveTo determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed <24 vs ≥24 weeks' gestation (early vs standard GDM).Design and SettingThis was a retrospective cohort study undertaken at the Royal Prince Alfred Hospital Diabetes Antenatal Clinic, Australia, between 1991 and 2011.Patients and InterventionsPregnant women (N = 3098) underwent an HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively.Main Outcome MeasureThe association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM.ResultsHbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia.ConclusionsBaseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort.
背景:妊娠期糖尿病(GDM)的患病率日益增加,需要进行风险分层,将有限的产前资源用于风险最高的人群。最近的证据表明,妊娠早期糖化血红蛋白(HbA1c≥5.9% (41 mmol/mol))可预测不良妊娠结局。目的:在接受治疗的多民族队列中,确定GDM患者不良妊娠结局的最佳HbA1c阈值,并确定诊断为5.9% (41 mmol/mol)的女性发生大胎龄(优势比[95%置信区间]= 2.7[1.5-4.9])、巨大儿(3.5[1.4-8.6])、剖宫产(3.6[2.1-6.2])和高血压疾病(2.6[1.1-5.8])的最大风险是否存在差异。在早期GDM中,HbA1c也有类似的关联;然而,较低的HbA1c与胎龄较小的最大风险(P趋势= 0.004)和新生儿低血糖的患病率相关。结论基线HbA1c >5.9% (41 mmol/mol)表明标准GDM患者发生大胎龄、巨大儿、剖宫产和高血压疾病的风险增加。尽管在早期GDM中也有类似的关联,但在该队列中,较高的HbA1c水平并不能充分体现风险限制的效用,不能作为分诊工具。
{"title":"Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes","authors":"A. Sweeting, G. Ross, J. Hyett, L. Molyneaux, K. Tan, M. Constantino, A. Harding, J. Wong","doi":"10.1210/jc.2016-2951","DOIUrl":"https://doi.org/10.1210/jc.2016-2951","url":null,"abstract":"Context\u0000The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes.\u0000\u0000\u0000Objective\u0000To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed <24 vs ≥24 weeks' gestation (early vs standard GDM).\u0000\u0000\u0000Design and Setting\u0000This was a retrospective cohort study undertaken at the Royal Prince Alfred Hospital Diabetes Antenatal Clinic, Australia, between 1991 and 2011.\u0000\u0000\u0000Patients and Interventions\u0000Pregnant women (N = 3098) underwent an HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively.\u0000\u0000\u0000Main Outcome Measure\u0000The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM.\u0000\u0000\u0000Results\u0000HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia.\u0000\u0000\u0000Conclusions\u0000Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort.","PeriodicalId":22632,"journal":{"name":"The Journal of Clinical Endocrinology & Metabolism","volume":"2010 1","pages":"150–156"},"PeriodicalIF":0.0,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86312820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 38
期刊
The Journal of Clinical Endocrinology & Metabolism
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