Reference values for serum levels of insulin-like growth factor (IGF-1) and IGF-binding protein 3 (IGFBP-3) and their ratio in Chinese adolescents

OBJECTIVE: To establish the reference values for serum levels of IGF-1 and IGFBP-3 and their ratio in Chinese adolescents aged 12-19 years. DESIGN AND METHODS: 2102 Chinese adolescents were randomly selected from all secondary schools in Hong Kong with 1734 having IGF-1 and IGFBP-3 levels as measured by automated chemiluminescent assays (IMMULITE 2000). LMS (Lambda-Mu-Sigma) method was used to generate reference percentile curves for IGF-1, IGFBP-3 and their ratio. RESULTS: After excluding participants with abnormal thyroid function, 798 boys and 894 girls were included in the analysis with a mean (+/-SD) age of 15.3 (+/-2.0) and 15.7 years (+/-2.0), respectively. Both serum IGF-1 and IGFBP-3 levels tended to be higher in girls than boys before the age of 16. In boys, there was progressive decline in IGF-1 after a pubertal peak at the age of 13-14. In girls, there was a similar decline after the age of 12. In both boys and girls, there was progressive age-dependent decline in IGFBP-3 after the age of 15-16. The pattern of changes for IGF-1/IGFBP-3 ratio was similar to that of the IGF-1 levels. CONCLUSIONS: These reference values of IGF-1 and IGFBP-3 in healthy adolescents should facilitate the clinical management of adolescents with GH-IGF axis disorders.     

Effects of octreotide on serum insulin-like growth factor I and insulin-like growth factor binding proteins in patients with cirrhosis

Hyperinsulinaemia and reduced insulin sensitivity are common features in patients with cirrhosis. Octreotide, a long-acting somatostatin analogue, is used in cirrhotic patients in the treatment of bleeding oesophageal varices. Octreotide has potent effects on the growth hormone (GH )/insulin-like growth factor I (IGF-I ) axis in healthy subjects, but the effects on the GH/IGF-I axis in patients with cirrhosis have been described only briefly. The effects of a 12 h infusion of octreotide (bolus 0.75 &#119 g/kg followed by 0.75 &#119 g/kg/h) in 25 subjects (normals n = 9, compensated cirrhotics n = 8, decompensated cirrhotics n = 8) were compared with those in placebo-treated controls (n = 19) during fasting conditions. IGF-I, free IGF-I, IGF binding proteins (IGFBPs), insulin, C-peptide, GH and glucose were measured. Insulin resistance was calculated using the HOMA method. Octreotide reduced levels of total IGF-I in patients with compensated cirrhosis (p = 0.03) and free IGF-I in decompensated cirrhosis (p < 0.01). Insulin resistance was significantly reduced in normal subjects, whereas the reduction in insulin resistance did not reach statistical significance in patients with cirrhosis. In normal subjects, octreotide increased the IGFBP-1 area under curve threefold (p < 0.01) and decreased IGFBP-3 levels (p < 0.01), but these effects were blunted in the cirrhotic patients. Similarly, the reduction of insulin and C-peptide was blunted in the cirrhotic patients, whereas a significant reduction in GH was demonstrated in all groups. The effects of octreotide on the GH/IGF-I axis are mitigated in patients with cirrhosis and this may be a reflection of relative hyperinsulinaemia during octreotide treatment in these patients.     

The influence of growth hormone substitution therapy on erythroid and myeloid progenitor cells and on peripheral blood cells in adult patients with growth hormone deficiency

It has been reported that hypophysectomized rats exhibit normochromic, normocytic anaemia. Pancytopenia with impaired DNA synthesis in the bone marrow can be restored in these hypophysectomized rats by syngeneic pituitary grafts placed under the kidney capsule or treatment with growth hormone (GH). Until now, adults with hypopituitarism have received adequate replacement therapy with thyroxine, cortisol and sex steroids, but not with GH. We therefore investigated the effects of GH replacement therapy on the proliferation and differentiation of erythroid and myeloid progenitor and peripheral blood cells in 11 adult patients with growth hormone deficiency in a double-blind, placebo-controlled study for the first 6 months of therapy. The placebo group showed no changes during the first 6 months without therapy in either insulin-like growth factor I (IGF-I) levels, erythroid and myeloid progenitor precursor cells or peripheral blood cells. After commencement of GH therapy, IGF-I levels rose significantly during 24 months of therapy from 75.3±13.5 to 225±34.7ngmL^?1 (P<0.001). Erythroid and myeloid progenitor precursor cells showed a steep and significant increase after 18 and 24 months of therapy (erythroid: from 10.7±3.5 to 261.4±79.8, P<0.02, after 18 months and to 276.8±149.8 × 10⁵ mononuclear cell colonies, P<0.03, after 24 months; granulocyte–macrophage colony-forming units: from 39.7±9.8 to 316.9±124.6, P<0.002, after 18 months and to 366±188.7×10⁵ mononuclear cell colonies, P<0.03, after 24 months), whereas the peripheral red and white blood cells exhibited only minimal non-significant changes. The principal regulators of erythropoiesis, such as erythropoietin, and parameters reflecting erythropoiesis in the peripheral blood, such as reticulocytes, remained almost unchanged throughout the whole study period. We therefore conclude that patients with GH deficiency do not have anaemia, but have haematopoietic precursor cells in the lower normal range, and that GH substitution therapy over a period of 24 months has a marked effect on erythroid and myeloid progenitor precursor cells but only negligible effects on peripheral blood cells in GH-deficient adults.     

Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia.

Insulin-like growth factors (IGFs) in blood form two complexes with specific binding proteins (BPs): a large, growth hormone (GH)-dependent complex with restricted capillary permeability, and a smaller complex, inversely related to GH, with high turnover of its IGF pool and free capillary permeability. The distribution of BPs and of IGFs I and II between these complexes was studied in sera from healthy adults treated with IGF I or/and GH and from patients with extrapancreatic tumor hypoglycemia. Like GH, IGF I administration raises IGF I and two glycosylation variants of IGFBP-3 in the large complex, but unlike GH drastically reduces IGF II. During IGF I infusion, IGFBP-3 appears in the small complex whose IGFBP-2 and IGF I increase three- to fivefold and fivefold, respectively. GH treatment, associated with elevated insulin levels, suppresses IGFBP-2 and inhibits its increase owing to infused IGF I. The small complex of tumor sera contains increased amounts of IGFBP-2 and -3, and two- to threefold elevated IGF II. Conclusions: low GH and/or insulin during IGF I infusion and in extrapancreatic tumor hypoglycemia enhance expression of IGFBP-2 and favor partition of IGFBP-3 into the small complex. Free capillary passage and high turnover of its increased IGF I or II pools may contribute to compensate for suppressed insulin secretion during IGF I infusion or to development of tumor hypoglycemia.     

老年2型糖尿病患者健康体适能的影响因素分析

目的：分析老年2型糖尿病（T2DM）健康体适能的影响因素及与有氧运动的关系,为老年T2DM运动疗法提供参考。方法：选择2021年1月至2022年6月在我院参加体检的老年T2DM患者125例为调查对象,分析有氧运动（方法、等级）、健康体适能评分,采用单多重线性回归分析老年T2DM患者健康体适能的影响因素。结果：125例老年T2DM患者器官功能、活动功能、躯体调适能力、健康体适能评分分别为（54.43±8.35）、（51.54±7.26）、（57.36±8.42）、（54.42±8.26）分。不同性别、年龄、病程、家庭经济状况、运动时间、运动频率、运动强度老年T2DM患者健康体适能评分比较,差异有统计学意义（P＜0.05）。影响老年T2DM患者器官功能的因素为年龄、经济状况、运动时间、运动频率（P＜0.05）;活动功能的影响因素为性别、年龄、运动时间、运动频率、运动强度（P＜0.05）;躯体调适功能的影响因素为年龄、病程、经济状况、运动时间、运动频率（P＜0.05）;健康体适能的影响因素为性别、年龄、经济状况、运动时间、运动频率（P＜0.05）。结论：老年T2DM患者健康体适能影响因素包括有氧运动时间与运动频率。开展运动时间＞60 min/d、运动频率＞5次/周、中等强度运动疗法有利于提高老年T2DM患者健康体适能。     

肝素及低分子肝素对脑血管病患者血中妊娠相关血浆蛋白A浓度的影响

目的 探讨临床脑血管疾病治疗中应用的肝素和低分子肝素对血清学标志物PAPP.A浓度的影响,为进一步准确评价PAPP-A的临床意义提供依据.方法 选取山东大学齐鲁医院2009年11月至2010年5月收入院的40例脑血管病患者,分别采集药物注射前后的血标本.按照治疗方法及肝素和低分子肝素的用药情况分成4组:A组,10例皮下注射低分子肝素抗凝患者,注射前、治疗第1天、第2天和第7天注射后3 h以及末次注射后24 h分别抽取静脉血.B组,10例未用低分子肝素抗凝患者,入院时、入院第1天、第2天和第7天抽取静脉血.C组,10名肝素抗凝支架治疗患者,造影前、注射肝素前、注射肝素后第3、5、15、40和100分钟从动脉鞘管抽取动脉血.D组,10例未用肝素抗凝造影患者,造影前和造影完成后分别从动脉鞘管抽取动脉血.用ELISA方法检测各组标本中PAPP-A浓度,分析不同处理组组间差异及组内各时间点间的差异.结果 A组患者PAPP-A 浓度呈时间依赖性,随着给药天数的增加逐渐从注射前的12.36(9.90～14.32)mIU/L升高至第7天21.80(23.50～19.73)mIU/L,差异有统计学意义(M=38.72,P<0.01).C组患者静脉注射肝素后PAPP-A浓度5 min内由12.86(9.67～14.05)mIU/L升高至51.56(44.20～66.00)mIU/L,差异有统计学意义(M=46.06,P<0.01).皮下注射低分子肝素1周后A组PAPP-A的浓度为21.80(23.50～19.73)mIU/L,高于B组的11.81(9.21～12.89)mIU/L,差异有统计学意义(U<0.001,P<0.01).C组静脉注射肝素15 min时PAPP-A的浓度为43.70(37.70～54.30)mIU/L,高于D组造影后的14.18(11.25～15.86)mIU/L,差异有统计学意义(U<0.001,P<0.01).皮下注射低分子肝素后血中PAPP-A的峰值比静脉注射肝素的峰值低,A组与C组分别为21.80(23.50～19.73)、51.56(44.20～66.00)mIU/L,差异有统计学意义(U=0.999,P<0.01).结论 脑血管疾病临床治疗中应用肝素和低分子肝素会导致血中PAPP-A浓度的升高,选用PAPP-A作为评价指标时应考虑药物的影响.

Abstract：

Objecfive To investigate the effects of treatment for cerebrovascular disorder patients with heparin and low molecular weight heparin(LMWH) on serum PAPP-A concentrations and provide the basis for evaluating the clinical significance of PAPP-A in the following study.Methods Forty cases with cerebrovascular disease from Qilu Hospital from November 2009 to May 2010 were collected in this study.Blood samples were taken before and after drug administration.All cases were divided into four groups according to situation of medication.Group A consisted of 10 patients who received subcutaneous LMWH anticoagulation therapy, and blood samples were collected before LMWH injection, three hours after subcutaneous LMWH anticoagulation therapy in the first day, the second day and the seventh day and 24 hours after the last injection. Group B consisted of 10 patients who did not receive LMWH therapy, and blood samples were collected immediately after admission, the first day, the second day and the seventh day after admission. Group C consisted of 10 patients with percutaneous carotid intervention who received intravenous heparin at the beginning of stenting, and blood samples were collected from the arterial sheath just before angiography and heparin administration, and at 3, 5, 15, 40 and 100 min after heparin administration. Group D consisted of 10 patients who received carotid angiography but LMWH-free therapy,and blood samples were collected from the arterial sheath just before and after angiography. Serum PAPP-A concentrations were analyzed by ELISA to evaluate the differences of intra-groups and differences at different time points of inter-groups. Results In group A, PAPP-A concentrations were time dependent and elevated gradually from 12. 36 (9. 90-14. 32) mIU/L before LMWH injection to 21.80 (23.50-19.73) mIU/L at the seventh day after injection (M=38. 72, P < 0.01 ). In group C, there was a rapid increase of PAPP-A concentration from 12. 86 ( 9. 67-14. 05 ) mIU/L to 51.56 ( 44. 20-66. 00 ) mIU/L within 5 min after intravenous heparin injection (M=46. 06, P <0. 01 ). The PAPP-A concentration of one week after LMWH administration in group A was 21.80 (23.50-19.73) mIU/L, significantly higher than that in group B [11.81 (9. 21-12. 89) mIU/L] (U<0. O01, P<0.01). The PAPP-A concentration at 15 min after heparin administration in group C was 43.70 (37.70-54. 30) mIU/L, significantly higher than that after angiography in group D [14. 18 (11.25-15. 86) mIU/L] ( U<0. 001, P <0. 01 ). The peak level of blood PAPP-A after subcutaneous LMWH injection was significantly lower than that after intravenous heparin injection. The concentrations in group A and C were 21.80 ( 23.50-19. 73 ) and 51.56 (44. 20-66. 00) mIU/L respectively, and had a significant difference ( U=0. 999, P < 0. 01 ) . Conclusions Both intravenous heparin and subcutaneous LMWH administration induce an increase in serum PAPP-A concentration. The effect of drug should be considered when PAPP-A is selected as an evaluation indicator.     

低分子肝素钠联合硫酸镁对重度子痫前期患者血清高敏C反应蛋白和D-二聚体的影响分析

目的探讨低分子肝素钠联合硫酸镁对重度子痫前期患者的血清高敏C反应蛋白(hs-CRP)、D-二聚体(D-D)水平的影响。方法选择该院接诊的100例重度子痫前期患者,通过随机数表法分为观察组(50例)和对照组(50例),对照组采用硫酸镁治疗,观察组在硫酸镁治疗的基础上联合低分子肝素钠治疗。观察两组患者治疗前后血清hs-CRP、D-D、收缩压以及舒张压的变化,比较平均治疗时间、终止孕周时间、临床疗效及并发症的发生率。结果治疗后,观察组hs-CRP,D-D水平均低于对照组,差异有统计学意义(P0.05);观察组收缩压、舒张压水平低于对照组,差异具有统计学意义(P0.05);观察组平均治疗时间,终止妊娠孕周时间均短于对照组,差异具有统计学意义(P0.05);观察组总有效率96.00%(48/50)高于对照组74.00%(37/50),并发症发生率6.00%(3/50)低于对照组24.00%(12/50),差异具有统计学意义(P0.05)。结论低分子肝素钠联合硫酸镁可以有效降低重度子痫前期患者体内hs-CRP和D-D水平,抑制炎性反应,使新生儿的预后得到改善,值得在临床上应用推广。     

2型糖尿病合并下肢血管病变患者网膜素-1与炎性因子检测的意义

目的探讨网膜素-1(omentin-1)与炎性因子与2型糖尿病(T2DM)患者下肢血管病变(LVD)的相关性。方法将126例T2DM患者分为T2DM组(68例)与T2DM+LVD组(58例),选择健康体检者40例纳入对照组,比较各组体质量指数(BMI)、腰臀比(WHR)、血压、空腹血糖(FBG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、血脂、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、omentin-1、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和超敏C反应蛋白(hs-CRP),分析血浆omentin-1水平与其他指标的相关性,分析omentin-1的影响因素和T2DM患者发生LVD的影响因素。结果 T2DM组与T2DM+LVD组BMI、WHR、DBP、2FBG hPG、HbA1c、TC、TG、LDL-C、FINS、HOMA-IR、TNF-α、IL-6、hs-CRP均高于对照组,T2DM+LVD组病程长于T2DM组,对照组、T2DM组和T2DM+LVD组DBP、HbA1c、LDL-C、TNF-α、IL-6、hs-CRP呈升高趋势,omentin-1、ABI呈降低趋势,差异均有统计学意义(P0.05);omentin-1与ABI呈正相关(P0.05),与FPG、HbA1c、LDL-C、TNF-α、IL-6、hs-CRP均呈负相关(P0.05);TNF-α、ABI、HbA1c是血浆omentin-1水平的独立影响因素;omentin-1、TNF-α、IL-6和HbA1c是T2DM患者发生LVD的影响因素。结论 omentin-1可能参与了T2DM患者LVD的发生和发展,其血浆水平不仅受到糖脂代谢的影响,还可能受到炎性因子的影响。     

ABCAl基因R219K多态性在新疆维吾尔族、汉族分布特征及与血脂水平关系

目的:探讨三磷酸腺苷结合盒转运蛋白A1(ABCA1)基因R219K多态性在新疆汉族和维吾尔族健康人群中的分布特征及与血脂水平的相关性。方法:采用聚合酶链反应-限制性片段长度多态性技术,对新疆640名汉族和468名维吾尔族健康体检者的ABCA1基因R219K多态性进行检测,比较2个民族基因型和等位基因的分布特征,并分析ABCA1基因R219K多态性与血脂水平的相关性。结果:ABCA1基因R219K多态性位点在汉族和维吾尔族KK的基因型频率(20.5%,14.3%)、RK基因型频率(51.1%,51.5%)及RR基因型频率(28.4%,34.2%)比较差异均有统计学意义(P<0.05)。2个民族K等位基因频率(46.0%,40.1%)和R等位基因频率(54.0%,59.9%)比较差异有统计学意义(P<0.05)。2个民族KK、RK基因型携带者较RR基因型携带者血清三酰甘油水平降低(P<0.05),维吾尔族KK基因携带者,汉族KK、RK基因型携带者血清高密度脂蛋白胆固醇水平高于RR基因型携带者,差异均有统计学意义(P<0.05)。结论:ABCA1基因R219K多态性在新疆维吾尔族、汉族之间存在差异,且该多态性与血清...     

慢加急性乙型肝炎肝衰竭患者Th1/Th2细胞的细胞因子变化及与肝功能指标的关系

目的利用流式细胞微球芯片捕获技术(CBA)检测慢加急性乙型肝炎肝衰竭(ACHBLF)患者辅助性T细胞1/2(Th1/Th2)分泌的细胞因子水平,探讨其在ACHBLF中变化的意义。方法收集33例ACHBLF、20例慢性乙型肝炎(CHB)患者血清及15名健康志愿者血清,CBA检测血清Th1/Th2细胞因子γ干扰素(IFN-γ)、白细胞介素2(IL-2)、白细胞介素4(IL-4)、白细胞介素6(IL-6)、白细胞介素10(IL-10)及肿瘤坏死因子α(TNF-α)水平,分析Th1/Th2细胞因子在ACHBLF患者血清中的变化。结果 ACHBLF患者外周血循环中TNF-α、IFN-γ、IL-4及IL-6的水平较CHB患者及健康对照者显著升高(P0.05);ACHBLF患者血清中IL-2及IL-10与CHB组和健康对照组比较,差异无统计学意义(P0.05)。ACHBLF患者血清中IL-4、IL-6、TNF-α及IFN-γ水平与总胆红素(TBil)、白蛋白(Alb)和凝血酶原活动度(PTA)间无明显相关性。结论 CBA可同时检测各种细胞因子,适合临床应用;ACHBLF患者TNF-α、IFN-γ、IL-4和IL-6的变化可能参与ACHBLF的发生和发展,未发现上述细胞因子与反映肝功能指标间的相关关系。     

抑郁症与强迫症患者治疗前后血清脑源性神经营养因子、白介素-2及白介素-6水平变化及其临床意义

目的探讨抑郁症与强迫症患者治疗前后血清脑源性神经营养因子(BDNF)、白介素-2(IL-2)、白介素-6(IL-6)水平变化及影响因素。方法患者按症状分为抑郁症组、强迫症组、对照组,每组30例。抑郁症组和强迫症组在帕罗西汀治疗基础上,配合心理治疗。酶联免疫吸附法(ELISA)检测3组血清BDNF、IL-2、IL-6水平。治疗前后进行量表评定,抑郁症状评定采用汉密尔顿抑郁量表(HAMD),强迫症状评定采用耶鲁-布朗强迫量表(Y-BOCS)。对抑郁症、强迫症患者血清BDNF、IL-2、IL-6水平与HAMD总分值、Y-BOCS总分值、病程、年龄、性别之间进行相关分析。结果治疗后抑郁症组血清BDNF水平较治疗前明显升高,IL-2、IL-6水平较治疗前明显降低,但BDNF水平仍明显低于对照组。治疗后强迫症组血清BDNF水平较治疗前明显升高,IL-2水平较治疗前明显降低,但BDNF水平仍明显低于对照组。抑郁症组血清BDNF水平与HAMD评分呈负相关(P<0.05),血清IL-2、IL-6水平与HAMD评分呈正相关。强迫症组血清BDNF水平与Y-BOCS评分呈负相关,血清IL-6与Y-BOCS评分呈正相关。结论 BDNF、IL-2、IL-6为抑郁症、强迫症的鉴别及诊疗提供可能依据。