Cardiovascular disease risk markers in children under 10 years of age and their relationship with serum concentrations of IGF-1, IGFBP-1, IGFBP-2 and IGFBP-3 / Marcadores de riesgo cardiovascular en niños menores de 10 años y su relación con niveles séricos de IGF-1, IGFBP-1, IG-FBP-2 e IGFBP-3

Abstract Introduction: Any type of nutritional imbalance experienced during childhood will affect the health of an individual, both in their childhood and their adulthood. Several studies have proved that there is an association between cardiovascular disease (CVD) risk and endocrine and lipid markers at early stages of life. Objective: To establish the relationship between nutritional status (IGF-1 and serum levels of its binding proteins IGFBP-1, IGFBP-2 and IGFBP-3), and CVD risk markers in students aged 7 to 9 years. Materials and methods: Cross-sectional observational study conducted in 84 children attending two schools from Bogotá D.C. and Soacha, Colombia, to identify the relationship between possible variations in CVD risk markers and nutritional status. Sexual development stage, lipid profile, anthropometric data, blood sugar levels and IGF-1 and IGFBP serum levels of all participants were measured. Statistical analysis was conducted using the Pearson's correlation coefficient, the analysis of variance (ANOVA), and the Kruskall-Wallis, Games-Howell and Dunnett's tests. The confidence interval and statistical significance were 95% and p<0.05, respectively. Results: IGFBP-1 and IGFBP-2 levels proportionally decreased as weight increased. An inverse correlation between both proteins and triglyceride levels was found, as well as a direct correlation with HDL cholesterol levels. Conclusions: Alterations in CVD risk markers can be identified during childhood. If said alterations are timely detected, it is possible to adopt preventive and therapeutic actions such as the promotion of public policies aimed at preventing childhood overweight and obesity, which in turn will reduce the risk of developing cardiovascular disease in adulthood.

Resumen Introducción. Los desequilibrios nutricionales en la infancia afectan la salud tanto en la niñez como en la adultez. Estudios previos demuestran la asociación de marcadores endocrinos y lipídicos con riesgo cardiovascular (RCV) desde edades tempranas. Objetivo. Establecer la relación entre estado nutricional (niveles séricos de IGF-1 y sus proteínas enlazantes IGFBP-1, IGFBP-2 e IGFBP-3) y marcadores de RCV en estudiantes de 7 a 9 años. Materiales y métodos. Estudio observacional comparativo transversal realizado en 84 niños de 2 colegios de Bogotá D.C. y Soacha, Colombia, para identificar la relación entre posibles variaciones de marcadores de RCV y estado nutricional. Se midieron los niveles de glucemia y niveles séricos de IGF-1 e IGFBP, el nivel de desarrollo sexual, el perfil lipídico y los valores antropométricos. Para el análisis estadístico se utilizaron el coeficiente de correlación de Pearson, un análisis de varianza (ANOVA) y las pruebas de Kruskal Wallis, Games-Howell y Dunnett. El intervalo de confianza fue del 95% y la significancia estadística, de p<0.05. Resultados. La reducción en los niveles de IGFB-1 e IGFBP-2 fue directamente proporcional al aumento de peso. Por otra parte, se observó una correlación inversa entre ambas proteínas y concentraciones de triglicéridos, y una directa con los niveles colesterol HDL. Conclusiones. Las alteraciones de marcadores de RCV se pueden identificar en la infancia. Si estas son detectadas a tiempo es posible adoptar medidas preventivas y terapéuticas como la promoción de políticas públicas dirigidas prevenir el sobrepeso infantil, lo que a su vez reducirá el riesgo de padecer enfermedades cardiovasculares en edades adultas.

Utilidad de la proteína de unión al factor de crecimiento similar a la insulina tipo 1 en la ruptura prematura de membrana / Utility of insulin-like growth factor-binding protein type 1 in premature membrane rupture

Introducción: Fercuentemente no disponemos de una clara evidencia de la pérdida de líquido amniótico observado por examen con espéculo, por lo que el diagnóstico de rotura prematura de membranas puede ser con frecuencia incierto, por lo que se necesitan pruebas de diagnóstico apropiadas y complementarias para la toma de decisiones. Objetivo: conocer la precisión diagnóstica de la proteína-1 de unión al factor de crecimiento similar a la insulina (IGFBP-1) en la rotura prematura de membranas al compararla con la medición del bolsilla mayor por ecografía y el Test de de Ferning. Material y métodos: 102 gestantes de 24 a 37 semanas con signos y/o síntomas de rotura de membranas fueron elegibles, fueron evaluadas con las pruebas IGFBP-1, ecografía y Test de Ferning. Resultados: Para el IGFBP-1 se obtuvo 95% de sensibilidad (S), 95% de especificidad (E), 95% de valor predictivo positivo (VPP) y 96% de valor predictivo negativo (VPN). Par el Test de Fernig se obtuvieron valores de 85%, 25%, 25% y 83% respectivamente. En tanto que para la ecografía los hallazgos fueron de 81%, 29%, 56% y 58% respectivamente. Conclusión: el ensayo IGFBP-1 fue el método más preciso para diagnosticar la ruptura prematura de membranas con la mayor sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo.

Introduction: We do not have clear evidence of the loss of amniotic fluid observed by speculum examination, so the diagnosis of premature rupture of membranes can often be uncertain and appropriate and complementary diagnostic tests are needed for decision making. Objective: to know the diagnostic accuracy of insulin-like growth factor-binding protein-1 (IGFBP-1) in the premature rupture of membranes when compared with the measurement of the greater pocket by ultrasound and the Ferning test. Material and methods: 102 pregnant women from 24 to 37 weeks with signs and / or symptoms of rupture of membranes were eligible, which were evaluated with the IGFBP-1, ultrasound and Ferning Test. Results: For IGFBP-1 95% sensitivity (S), 95% specificity (E), 95% positive predictive value (PPV) and 96% negative predictive value (NPV) were obtained. For the Ferning Test values of 85%, 25%, 25% and 83% respectively were obtained. While for ultrasound the findings were 81%, 29%, 56% and 58% respectively. Conclusion: the IGFBP-1 assay was the most accurate method to diagnose the premature rupture of membranes with the highest sensitivity, specificity, positive predictive value and negative predictive value.

The diagnostic value of serum AMH, IGF-1 and IGFBP-1 levels in polycystic ovarian syndrome / 中国基层医药

Objective To explore the relation between serum AMH,IGF-1 and IGFBP-1 levels and polycystic ovarian syndrome (PCOS) and its clinical significance.Methods Serum levels of AMH,IGF-1 and IGFBP-1 were measured by ELISA in 80 patients with PCOS and 80 healthy subjects.Results The levels of serum AMH,IGF-1,IGFBP-1 in PCOS group were (7.18 ± 1.50) ng/L,(200.85 ± 27.78) ng/L,(4.05 ± 0.65) ng/L respectively,which in the control group were (3.70 ± 1.01) ng/L,(110.58 ± 12.50) ng/L,(8.16 ± 1.39) ng/L.The serum levels of AMH,IGF-1 in the PCOS group were significandy higher than those in the control group(t =13.14,26.80,P ＜ 0.01),while the serum level of IGFBP-1 in the PCOS group was significantly lower than that in the control group(t =16.28,P ＜0.01).The serum levels of AMH,IGF-1,IGFBP-1 in patients with obese group were (7.18 ± 1.50) ng/L,(200.85 ± 27.78) rng/L,(4.05 ± 0.65)ng/ L respectively,which in the non-obese group were (15.52 ± 2.41) ng/L,(143.85 ± 15.61) ng/L,(6.75 ± 0.93) ng/L.The serum level of IGF-1 in the obese group was significantly higher than that in the non-obese group(t =10.87,P ＜0.01),while the serum levels of AMH and IGFBP-1 in the obese group were significandy lower than those in the non-obese group(t =18.98,15.27,P ＜0.01).Conclusion Serum AMH,IGF-1 and IGFBP-1 may be involved in the pathogenesis and obesity of PCOS,which may be associated with the pathogenesis of PCOS.

Value of non phosphorylated insulin -like growth factor binding protein -1 in cervical vaginal excretion and residual amniotic fluid index monitoring in the diagnosis of premature rupture of membranes / 中国基层医药

Objective To explore the method of rapid diagnosis preterm premature rupture of membrane (PPROM)and prognosis factors of residual amniotic fluid in mother and infant through monitoring nonphosphorylated insulin -like growth factor binding protein -1 (IGFBP -1)and the residual amniotic fluid index (AFI)of the cervi-covaginal secretions from PPROM women.Methods 96 cases of PPROM were tested IGFBP -1 of cervicovaginal secretions,AFI were tested by abdominal ultrasound through fast chromatography methods,and the cause was ana-lyzed.The pregnancy outcome and neonatal prognosis were compared.Results 92 cases positive of IGFBP -1 were diagnosed with PPROM.The risk factors of PPROMwere mainly reproductive tract infections,abortion,induced labor history and unknown causes (including no evidence of infection,fetal membrane dysplasia unclear or other factors), the twins,multiplets,macrosomia,breech or cephalopelvic disproportion,gestational hypertension disease,uterine fibroids or deformity,malnutrition and polyhydramnios.In the 92 patients with PPROM pregnant women,the duration from premature rupture of membrane to delivery was (105.7 ±13.9)h,cesarean section rate was 51.1%,fever rate of pregnant women was 7.6%,the rate of placental abruption was 4.3%,the rate of fetal distress was14.1%,perinatal infection rate was 21.7%,and neonatal asphyxia rate was 7.6%,the neonatal mortality was 7.6%.To compare the AFI≤40mm group with AFI >40 mm group,the duration from premature rupture of membrane to delivery was short-ened remarkably (t =10.904,P <0.05),the neonatal mortality rate was significantly increased (χ2 =4.359,P <0.05).Conclusion Measurement of IGFBP -1 and AFI in cervicovaginal secretions can rapid diagnosis PPROMand evaluate the results of pregnancy and neonatal prognosis,and can guide clinical improvement of pregnancy safety and reduce neonatal mortality.

Insulin-like growth factor (IGF)-I and IGF binding proteins axis in diabetes mellitus

Increasing evidence suggests an important role of the insulin-like growth factor (IGF)-IGF binding protein (IGFBP) axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM). Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.

Relationship among serum levels of suppressors of cytokine signaling-3, insulin-like growth factor binding ;protein-1 and hyperglycemia in critically ill children / 中华实用儿科临床杂志

Objective To investigate the relationship among serum levels of suppressors of cytokine signaling-3(SOCS-3),insulin-like growth factor binding protein-1(IGFBP-1) and hyperglycemia in critically ill children. Methods The 64 critically ill children who suffered from sepsis,after surgical repair of congenital heart dis-ease by extracorporeal circulation, and after surgery of severe traumatic from January 2009 to January 2012 in Depart-ment of Pediatric Intensive Care Unit( PICU) of Guangzhou Women and Children′s Medical Center were selected as the research object. According to the blood glucose levels on admission, the 64 children were divided into the normal glu-cose group and the hyperglycemia group. The 15 cases of healthy children in the same period in Guangzhou Women and Children′s Medical Center were selected as the healthy control group. The levels of blood glucose,insulin,SOCS-3,IG-FBP-1 and insulin resistance index( HOMA-IR) were measured and compared among groups when they were on ad-mission. Results (1) The blood glucose of the hyperglycemia group was significantly higher than those in the normal glucose group and the healthy control group[(9. 83±2. 48) mmol/L vs (4. 82±0. 76) mmol/L,(4. 49±0. 81) mmol/L] (P0. 05). (4) The blood glucose was positively correlated with the insulin and HOMA-IR(r=0. 455,0. 773,P0. 05). Con-clusions In the critically ill children,hyperglycemia was related to the insulin resistance which can not be evaluated through changes in serum levels of SOCS-3 and IGFBP-1. In addition,it cannot be excluded that the critically ill chil-dren may have insulin resistance and pancreaticβ-cell dysfunction simultaneously.

Negative acute phase proteins in patients with chronic urticaria / 中华皮肤科杂志

Objective To investigate the relationship between negative acute phase proteins and chronic urticaria (CU).Methods Fifty patients with CU were enrolled into this study,and divided into three grades,i.e.,mild (grade 1),moderate (grade 2) and severe (grade 3) according to symptoms.Twenty-eight health checkup examinees served as the control group.Immunoturbidimetry was performed to determine serum levels of prealbumin (PA) and transferrin (TRF).Enzyme-linked immunosorbent assay was conducted to measure serum levels of insulinlike growth factor-1 (IGF-1) and tumor necrosis factor-α (TNF-α).Statistical analysis was carried out to assess differences in these indices between these two groups,the relationship among these indices and between these indices and disease severity.Results Compared with the control group,the patients with CU showed reduced serum levels of PA ((229.99 ± 54.16) vs.(272.06 ± 36.42) mg/L,t =3.667,P ＜ 0.05) and IGF-1 ((177.23 ± 46.48) vs.(239.88 ± 45.16) μg/L,t =5.748,P＜ 0.05),but higher serum levels of TNF-α ((25.39 ± 11.01) vs.(14.13 ± 6.12) ng/L,t =4.989,P＜ 0.05),and similar serum levels of TRF ((2.48 ± 0.49) vs.(2.48 ± 0.25) g/L,P＞ 0.05).The serum level of PA showed a significant negative correlation with that of TNF-α (r =-0.312,P ＜ 0.05),as well as with disease severity (r =-0.635,P ＜ 0.01),whereas the serum level of TNF-α showed a significant positive correlation with disease severity (r =0.409,P ＜ 0.01),and no statistical correlation was found between the remaining indices (all P ＞ 0.05) in the patients with CU.Conclusions Serum levels of some negative acute phase proteins decrease and negatively correlate with disease severity in patients with CU.Acute phase response may be involved in the occurrence of CU.

Predição do parto prematuro: avaliação sequencial do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile / Preterm birth prediction: sequential evaluation of the cervix and the test for phosphorylated protein-1 linked to insulin-like growth factor

OBJETIVOS: Averiguar a utilidade da medida do comprimento do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile (phIGFBP-1), realizados de maneira sequencial, na predição do parto prematuro e a existência de correlação entre os testes. MÉTODOS: Foram submetidos a análise secundária os dados de 101 gestantes assintomáticas com antecedente de prematuridade. A medida ultrassonográfica do comprimento do colo e o teste para phIGFBP-1 foram realizados em paralelo a cada três semanas, entre a 24ª e a 34ª semana. O melhor valor de corte do colo uterino para cada avaliação foi estabelecido por meio de curva ROC, e ambos os testes foram comparados entre si por meio de testes não paramétricos. Foram obtidas a sensibilidade, a especificidade e os valores preditivos de cada teste e da associação dos exames para a ocorrência de parto antes de 37 semanas. RESULTADOS: Houve 25 partos prematuros (24,8%). O comprimento do colo apresentou maior sensibilidade e foi capaz de predizer o parto prematuro em todas as avaliações, com acurácia semelhante em diferentes idades gestacionais. O teste para phIGFBP-1 não foi útil na 24ª semana, porém foi capaz de predizer independentemente a prematuridade na 27ª à 30ª e 33ª semana. A associação dos exames elevou a sensibilidade (81,8%) e o valor preditivo negativo (93,7%) quando comparada à utilização isolada dos testes. O comprimento cervical médio foi menor em gestantes com teste positivo. CONCLUSÕES: Tanto o comprimento cervical quanto o teste para phIGFBP-1 foram capazes de predizer independentemente o parto prematuro, e a associação sequencial de ambos os exames apresentou elevada sensibilidade e alto valor preditivo negativo.

PURPOSE: To investigate the usefulness of the measurement of cervical length and of the test for phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) performed sequentially in the prediction of preterm birth and the correlation between tests. METHODS: We analyzed data from 101 asymptomatic pregnant women with a history of premature delivery. The ultrasound measurement of cervical length and phIGFBP-1 test were performed in parallel every three weeks, between 24 and 34 week. The best cutoff value for each cervical evaluation was established by the ROC curve, and the two tests were compared using nonparametric tests. We determined the sensitivity, specificity and predictive values of each test and of the association of the exams for the occurrence of delivery before the 37th weeks. RESULTS: There were 25 preterm births (24.8%). The cervix length showed the highest sensitivity and was able to predict preterm birth in all evaluations, with similar accuracy at different gestational ages. The test for phIGFBP-1 was not helpful at 24 weeks, but was able to predict prematurity when performed at 27, 30 and 33 weeks. The combination of tests increased the sensitivity (81.8%) and negative predictive value (93.7%) when compared to the separate use of each test. The mean cervical length was lower in women with a positive test. CONCLUSIONS: Both cervical length and the test for phIGFBP-1 were able to predict premature delivery, and sequential combination of both tests showed a high sensitivity and high negative predictive value.

The Value of Insulin Like Growth Factor Binding Protein-1 of Cervicovaginal Secretion in the Delayed Pregnancy Termination / 中国医师杂志

Objective To study the value of insulin like growth factor binding protein-1 of cervicovaginal secretion in the delayed pregnancy termination. Methds Phosphorylated isoforms of IGFBP-1 in cervicovaginal secretion of 202 delayed pregnant women were measured by immmmunochromatography. Results In the IGFBP-1 positive group. The rate of successful pregnant termination in three days was 91 2%, while in IGFBP-1 negative group, the rate of that was 41 8%..There was statistically significant diference in the rate of successful pregnant termination between the two groups(P

Transforming Growth Factor-alpha Regulation of Insulin-like Growth Factor-II, Insulin-like Growth Factor Binding Protein-1 and 3 secretion and Epidermal Growth Factor receptor expression in human luteinized granulosa cells / 대한산부인과학회잡지

OBJECTIVE: To investigate the effects of transforming growth factor (TGF)-alpha on insulin-like growth factor (IGF)-II, insulin-like growth factor binding protein (IGFBP)-1, and 3 secretion and epidermal growth factor (EGF) receptor expression in cultured human luteinized granulosa cells. MATERIALS AND METHODS: Human luteinized granulosa cells were obtained from follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing in vitro fertilization and cultured for 72 hours with TGF-alpha at concentration of 1.0, 10.0, 100.0 ng/ml. The luteinized granulosa cells not treated with TGF-alpha served as control. The secretion of IGF-II, IGFBP-1 and 3 were determined in conditioned media by immunoradiometric assay (IRMA) and reverse transcription-polymerase chain reaction (RT-PCR) was performed for EGF receptor mRNA expression. RESULTS: The cell numbers of 1.0 and 10.0 ng/ml supplement groups were significantly decreased compared to control (p<0.05, p<0.05, respectively), although the cell viabilities were similar in all groups. IGF-II levels were significantly higher in TGF-alpha treatment group at 1.0 and 10.0 ng/ml (p<0.01, p<0.01, respectively), but lower in 100.0 ng/ml (p<0.01). However, the concentrations of IGFBP-1, and 3 per one granulosa cell in each group were no statistically significant differences among the groups. The mRNA concentration of EGF receptor in cultured human luteinized granulosa cells were not significantly different among the groups. CONCLUSION: This study suggests that TGF-alpha regulate intrafollicular bioavailable IGF-II levels, by which TGF-alpha might involved luteinizations. However, TGF-alpha may not directly regulate EGF receptor mRNA expression in cultured human luteinized granulosa cells.

On the serum leptin and IGF-Ⅰ levels in patients with polycystic ovary syndrome / 中华内分泌代谢杂志

Serum levels of leptin, insulin like growth factor (IGF)Ⅰ, IGF binding protein 1(IGFBP1), fasting insulin (FINS) were determined in 36 patients with polycystic ovary syndrome (PCOS) and 26 control subjects. The results showed that serum leptin, IGF Ⅰ, FINS in PCOS patients were significantly higher than those in control subjects, and serum IGFBP1 level was significantly lower than that in control subjects. Serum leptin was positively correlated with FINS in PCOS patients.

Serum Insulin-like Growth Factors and their Binding Proteins in the Women With Polycystic Ovary / 대한산부인과학회잡지

OBJECTIVE: The involvement of IGF system in hyperandrogenism and abnormal follicular development is controversial. This study is to assess whether IGF system contribute to it in the women with polycystic ovary(PCO). METHODS: Baseline serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone (T), androstenedione (ADD), prolactin, thyroid stimulating hormone (TSH), free insulin-like growth factor(IGF)-I, free IGF-II, insulin-like growth factor binding protein(IGFBP)-1, and IGFBP-3 were measured in twelve healthy regularly cycling volunteers and forty-two women with PCO then, the changes of baseline serum levels were evaluated after laparoscopic ovarian electrocauterization in nine PCO patients. In addition, the expression pattern of IGF-I and IGF-II was examined in the ovary of control and PCO group. RESULTS: Baseline levels of LH, ADD, free IGF-II, and IGFBP-3 were significantly higher in PCO group. However, there were no significant differences in the levels of free IGF-I and IGFBP-1, although free IGF-I showed decreasing tendency in PCO group. And there was a significant positive correlation between the LH and free IGF-II level in the PCO(P=0.011, r2=0.3899), but not in the control. After ovarian electrocauterization, LH, T, and ADD levels decreased, and free IGF-I and IGFBP-3 level increased. While free IGF-II and IGFBP-1 level showed no significant changes. In the ovary, expression of both IGFs showed similar pattern in normal and PCO ovaries. CONCLUSIONS: The elevated IGFBP-3 level may alter the bioavailability of IGF(s) in the PCO. The change in IGF-I level and resumption of ovulation after electrocauterization, suggest a possible role of IGF system in the impairment of follicular development in the PCO.

Effects of Insulin-like Growth Factor-Ⅰ and Insulin-like Growth Factor Binding-protein 1 on Development of Ovarian Follicles during Superovulation Cycle / 中华妇产科杂志

Objective To investigate the effects of insulin-like growth factor Ⅰ (IGF-Ⅰ) and insulin-like growth factor binding-protein 1 (IGFBP-1) on development of ovarian follicles during gonadotropin stimulation in in-vitro fertilization (IVF) program. Methods Enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay were used to determine the levels of IGF-Ⅰ, IGFBP-1 and estradiol (E 2) in serum and follicular fluid obtained during oocyte pick-up (OPU) in 32 IVF-embryo transfer cycles. Results (1) Serum IGFBP-1 levels increased with growth of follicles [(3 5?1 0) ?g/L during OPU, (2 1?0 5) ?g/L before stimulation, P 0 05]. Significant positive correlation was found between serum IGFBP-1 and serum E 2 [(3 5?1 0) ?g/L, (3 293? 1 361) pmol/L, r =0 41, P

A decrease in circulating levels of immunoreactive insulin-like growth factor binding protein-1 (IGFBP-1) after endometrial ablation using a gynecologicresectoscope

To determine how endometrium alone would contribute to maintaining the circulating levels of Insulin-like growth factor binding protein-1 in vivo, serum immunoreactive IGFBP-1 levels were measured in 19 patients undergoing endometrial ablation using gynecologic resectoscopy. After endometrial ablation there was a significant decrease in the mean levels of circulating IGFBP-1, which was not correlated with the menstrual cycle. This result indicates that the endometrium is one of the sources of the circulating IGFBP-1.