Physical Activity at Different Life Stages and Its Consequence on the Initial Immunization and Inflammatory Response Against COVID-19.

BACKGROUND: To evaluate the influence of previous physical activity (PA) during childhood, adolescence, and current PA practice on the production of antibodies and inflammatory response between the first and second doses of the COVID-19 vaccine. METHODS: Fifty-nine men and 56 women were evaluated before the first vaccine, and 12 weeks later, blood samples were taken to quantify production of anti-severe acute respiratory syndrome coronavirus-2 immunoglobulin G antibodies and cytokines. Previous PA during childhood and adolescence was self-referred, and current PA was assessed using the International Physical Activity Questionnaire. RESULTS: A positive and significant association was observed only between PA practice during adolescence and an increase in antibody production in adulthood (ß = 2012.077, 95% confidence interval, 257.7953-3766.358, P = .025). Individuals who practiced PA during adolescence showed higher production of antibodies between the first and second vaccine dose compared to nonpractitioners (P = .025) and those that accumulated ≥150 minutes per week of current moderate-vigorous PA (MVPA), and presented higher antibody production in relation to who did <150 minutes per week of MVPA (P = .046). Individuals that were practitioners during childhood produced higher G-CSF (P = .047), and those that accumulated ≥150 minutes per week of current MVPA demonstrated lower IP-10 levels (P = .033). However, PA practitioners during adolescence presented higher G-CSF (P = .025), IL-17 (P = .038), IL-1RA (P = .005), IL-1ß (P = .020), and IL-2 (P = .026) levels. CONCLUSION: Our results suggest that adults that accumulated at least 150 minutes of MVPA per week or practiced PA during adolescence developed an improved immune and inflammatory response against COVID-19 vaccination.

Association between phase angle and adverse clinical outcomes in hospitalized patients with COVID-19: A systematic review.

Phase angle, obtained by bioelectrical impedance, is an indicator of cellular integrity and has been proposed as a prognostic parameter in patients who are critically ill. This systematic review aimed to evaluate the association between phase angle and adverse clinical outcomes in hospitalized patients with coronavirus disease-2019 (COVID-19). An extensive literature search was performed in the MEDLINE/PubMed, Embase, and Web of Science databases, with interest in observational studies evaluating the association between phase angle and adverse clinical outcomes in individuals aged ≥18 years hospitalized with COVID-19. Studies were independently selected by two reviewers, according to eligibility criteria. Subsequently, data were extracted and presented in a qualitative synthesis. The evaluation of the quality of the studies was performed according to the Newcastle-Ottawa scale. The full methodology was published in PROSPERO (ID CRD42022306177). A total of 392 articles were identified, resulting in seven selected studies, of which six were prospective cohorts and one was retrospective. In the quality assessment, six studies obtained scores equal to or greater than seven, indicating a low risk of bias. A total of 750 participants composed the samples of the selected studies. Five studies reported an independent association between phase angle and adverse clinical outcomes during hospitalization for COVID-19, with emphasis on prolonged hospitalization and mechanical ventilation and higher mortality in patients with a lower phase angle. Thus, phase angle measurement can be useful in the early identification of risks in patients hospitalized with COVID-19, for the purpose of adequacy of clinical management.

Parental vaccine hesitancy and concerns regarding the COVID-19 virus.

PURPOSE: This study assessed parental vaccine hesitancy in a metropolitan area of the United States. The study aimed to determine what characteristics and contributing factors influenced parental vaccine hesitancy and concerns regarding COVID-19. DESIGN AND METHODS: An online survey was used to recruit 93 parents to answer demographic and vaccine hesitancy information. Vaccine hesitancy was measured using the Parent Attitudes about Childhood Vaccines survey. The study was conducted between June 2020 and September 2020 during the COVID-19 pandemic. RESULTS: The rate of vaccine hesitancy was 15%. One hundred percent of vaccine hesitant parents were mothers, at least 30 years of age, married, and had completed at least some college. When characteristics of vaccine hesitant parents were compared to non-hesitant parents, the hesitant parents reported having more children, with 93% reporting two or more children compared to only 74% of non-hesitant parents (p = 0.046). Fifty percent of hesitant parents reported no concerns regarding COVID-19 compared to only 20% of non-hesitant parents (p = 0.006), and significantly less hesitant parents reported willingness to have their children receive a safe, effective COVID-19 vaccine if it were available compared to non-hesitant parents (p < 0.001). CONCLUSIONS: Our findings indicate that older mothers with two or more children are more likely to be vaccine hesitant and this hesitancy extends to the current COVID-19 pandemic. PRACTICE IMPLICATIONS: Healthcare providers can use the results of this study to identify parents at risk for vaccine hesitancy and initiate individualized education to promote on-time childhood vaccination.

Effectiveness of rectal indomethacin in the prevention of acute pancreatitis after endoscopic retrograde cholangiopancreatography in unselected patients

BACKGROUND AND AIMS: several studies have shown that rectal indomethacin decreases the risk of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, in recent studies, its effectiveness is being questioned, especially in average risk patients. Our principal aim was to evaluate the efficacy of rectal indomethacin prophylaxis in the development of post-ERCP pancreatitis (PEP). METHODS: a retrospective cohort study was conducted at a third-level university hospital. Data was collected from every patients who underwent ERCP between January 2014 and June 2016. After February 2015, all patients received 100 mg of rectal indomethacin prior to ERCP. We analyzed groups, with indomethacin and without indomethacin, in unselected patients. RESULTS: a total of 524 patients were analyzed, with a mean age of 71.1 ± 17.0 (standard deviation [SD]) years. Of the total number of patients, 393 (75%) had an average risk; 277 received rectal indomethacin prior to ERCP, while 247 did not. In the group with indomethacin, 12 patients developed PEP (4.33%) versus ten in the indomethacin-free group (4.04%) (OR 1.33; 95% confidence interval [CI], 0.52-3.40; p = 0.56). Severe-moderate PEP developed in seven patients (2.52%) in the indomethacin group and in two patients (0.81%) in the indomethacin-free group (p = 0.24). Previous sphincterotomy was a protective factor (OR 0.02; 95% CI, 0.02-0.2; p = 0.001) and age < 45 years was a risk factor: (OR 3.43; 95% CI, 1.14-10.32; p = 0.03). CONCLUSIONS: rectal indomethacin does not appear to decrease the risk of developing PEP in unselected patients

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Effectiveness of rectal indomethacin in the prevention of acute pancreatitis after endoscopic retrograde cholangiopancreatography in unselected patients.

BACKGROUND AND AIMS: several studies have shown that rectal indomethacin decreases the risk of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, in recent studies, its effectiveness is being questioned, especially in average risk patients. Our principal aim was to evaluate the efficacy of rectal indomethacin prophylaxis in the development of post-ERCP pancreatitis (PEP). METHODS: a retrospective cohort study was conducted at a third-level university hospital. Data was collected from every patients who underwent ERCP between January 2014 and June 2016. After February 2015, all patients received 100 mg of rectal indomethacin prior to ERCP. We analyzed groups, with indomethacin and without indomethacin, in unselected patients. RESULTS: a total of 524 patients were analyzed, with a mean age of 71.1 ± 17.0 (standard deviation [SD]) years. Of the total number of patients, 393 (75%) had an average risk; 277 received rectal indomethacin prior to ERCP, while 247 did not. In the group with indomethacin, 12 patients developed PEP (4.33%) versus ten in the indomethacin-free group (4.04%) (OR 1.33; 95% confidence interval [CI], 0.52-3.40; p = 0.56). Severe-moderate PEP developed in seven patients (2.52%) in the indomethacin group and in two patients (0.81%) in the indomethacin-free group (p = 0.24). Previous sphincterotomy was a protective factor (OR 0.02; 95% CI, 0.02-0.2; p = 0.001) and age < 45 years was a risk factor: (OR 3.43; 95% CI, 1.14-10.32; p = 0.03). CONCLUSIONS: rectal indomethacin does not appear to decrease the risk of developing PEP in unselected patients.

Normal values for water-perfused esophageal high-resolution manometry.

BACKGROUND: Normal values for water-perfused esophageal high-resolution manometry have still not been established in our environment, despite its generalized use and the recommendation to determine reference values for each Motility Unit based on their equipment. Normal values established with solid-state highresolution manometry are currently being used as reference values for water-perfused high-resolution manometry. OBJECTIVES: To obtain normal values for water-perfused esophageal high-resolution manometry, based on the esophageal motility analysis of healthy subjects. METHODS: 16 healthy volunteers without history of digestive complaints or esophageal symptoms were included. 22-channel water-perfused high-resolution manometry was performed. RESULTS: Normal values were calculated as 5th-95th percentile ranges for the following parameters; upper esophageal sphincter resting pressure (UESRP) (40-195 mmHg); upper esophageal sphincter residual pressure (UESResP) (30-115 mmHg), contractile front velocity (CFV) (2.4-7.1 cm/s), distal contractile integral (DCI) (285-2820 mmHg.s.cm), distal contraction latency (DL) (6.1-10.9 s), intrabolus pressure (IBP) (7-19 mmHg), integrated relaxation pressure (IRP 4s) (2-20 mmHg), lower esophageal sphincter resting pressure(LESRP) (5-54 mmHg), esophageal shortening (Es) (0.3-1.3 cm) and lower esophageal sphincter lift (LESL) (0,1-1,2 cm). CONCLUSION: Normal values for the most important parameters (such as IRP 4s, DL and CFV), obtained using a 22-channel waterperfused system resemble previously published data from other perfusion devices. However, there exist small but significant variations compared with values established with solid-state highresolution manometry. Thus, when using water-perfused catheters, caution is required when normative values are used that were established with solid-state catheters.

Valores de referencia de manometría esofágica de alta resolución mediante sistema de perfusión / Normal values for water-perfused esophageal high-resolution manometry

ANTECEDENTES: los valores de referencia de la manometría esofágica de alta resolución mediante sistema de perfusión aún no han sido establecidos en nuestro medio, a pesar de su empleo generalizado en múltiples Unidades de Motilidad y la recomendación de determinar valores de referencia propios de cada Unidad en función de sus equipos. Actualmente se utilizan como referencia los valores de normalidad de la manometría de alta resolución en estado sólido. OBJETIVOS: el objetivo de este estudio es establecer los valores de normalidad para la manometría de alta resolución de perfusión de 22 canales a partir del análisis de la motilidad esofágica de individuos sanos. MÉTODOS: se incluyeron 16 voluntarios sanos, sin patología digestiva ni síntomas esofágicos, a los que se realizó una manometría de alta resolución mediante sistema de perfusión de 22 canales. RESULTADOS: los datos vienen referidos como la media y el rango comprendido entre los percentiles 5 y 95. Los percentiles 5 y 95 de cada uno de los parámetros fueron de 40-195 mmHg para la presión de reposo del esfínter esofágico superior (PRESS), 30-115 mmHg para la presión residual del esfínter esofágico superior (PResEES), 2,4-7,1 cm/s para la velocidad de frente contráctil (VFC), 285-2.820 mmHg.s.cm para la integral contráctil distal (ICD), 6,1-10,9 s para la latencia distal (LD), 7-19 mmHg para la presión intrabolo (PIB), 2-20 mmHg para la presión de relajación integrada a los 4 segundos (PRI4s) y 5-54 mmHg para la presión de reposo del esfínter esofágico inferior (PREEI). Los percentiles 5 y 95 del acortamiento esofágico (aE) fueron 0,3-1,3 cm y del ascenso del esfínter esofágico inferior (aEEI) 0,1-1,2 cm. CONCLUSIÓN: los rangos de normalidad obtenidos mediante sistema de perfusión de 22 canales para los parámetros manométricos más importantes (PRI4s, LD, VFC) son similares a los previamente publicados con equipos de perfusión, existiendo variaciones pequeñas, pero significativas, respecto a los valores establecidos por equipos de estado sólido

BACKGROUND: Normal values for water-perfused esophageal high-resolution manometry have still not been established in our environment, despite its generalized use and the recommendation to determine reference values for each Motility Unit based on their equipment. Normal values established with solid-state highresolution manometry are currently being used as reference values for water-perfused high-resolution manometry. OBJECTIVES: To obtain normal values for water-perfused esophageal high-resolution manometry, based on the esophageal motility analysis of healthy subjects. METHODS: 16 healthy volunteers without history of digestive complaints or esophageal symptoms were included. 22-channel water-perfused high-resolution manometry was performed. RESULTS: Normal values were calculated as 5th-95th percentile ranges for the following parameters; upper esophageal sphincter resting pressure (UESRP) (40-195 mmHg); upper esophageal sphincter residual pressure (UESResP) (30-115 mmHg), contractile front velocity (CFV) (2.4-7.1 cm/s), distal contractile integral (DCI) (285-2820 mmHg.s.cm), distal contraction latency (DL) (6.1-10.9 s), intrabolus pressure (IBP) (7-19 mmHg), integrated relaxation pressure (IRP 4s) (2-20 mmHg), lower esophageal sphincter resting pressure (LESRP) (5-54 mmHg), esophageal shortening (Es) (0.3-1.3 cm) and lower esophageal sphincter lift (LESL) (0,1-1,2 cm). CONCLUSION: Normal values for the most important parameters (such as IRP 4s, DL and CFV), obtained using a 22-channel waterperfused system resemble previously published data from other perfusion devices. However, there exist small but significant variations compared with values established with solid-state highresolution manometry. Thus, when using water-perfused catheters, caution is required when normative values are used that were established with solid-state catheters

Accelerated early pubertal progression, ovarian morphology, and ovarian function in prospectively followed low birth weight (LBW) girls.

AIM: To compare pubertal development in age-matched healthy girls born with low birth weight (LBW) or appropriate birth weight for gestational age (AGA). SUBJECTS AND METHODS: Girls with breast in Tanner stage II and normal body mass index were followed for 3 years with a complete physical exam, bone age, pelvic ultrasound, and measurement of gonadal hormones using a leuprolide test. RESULTS: Forty-one girls (AGA 25/LBW 16) were followed up for 3 years. By 3 years, they had similar bone age, adjusted height, and body composition. In LBW girls, breast Tanner stage advanced faster during the first 2 years of follow-up, which was associated with higher serum androgens. Hirsutism score, ovarian volume, and number of follicles between AGA and LBW were not different nor was age of menarche. By the third year, basal and poststimulated levels of gonadotropins and androgens anti-Müllerian hormone and inhibin B were similar in both groups and did not show differences related to birth weight or degree of catch-up growth. CONCLUSION: LBW recruits showed a slightly faster breast development but no differences in androgen excess signs, internal genitalia, and gonadal hormonal patterns.

Cytoplasmic and nuclear STAT3 in GH-stimulated fibroblasts of children with idiopathic short stature.

BACKGROUND: STAT5, which plays an important role in GH signal transduction, has been studied extensively in children with growth retardation, but there is scarce information regarding STAT3. AIM: We determined total and phosphorylated STAT3 after GH stimulation in fibroblasts from children with idiopathic short stature (ISS) and control children with normal stature. SUBJECTS AND METHODS: We studied 15 prepubertal children (age 7.6 ± 0.4 years) with short stature (height -2.8 ± 0.2 SDS), decreased growth velocity (10 ng/ml to the clonidine stimulation test and decreased serum IGF-I concentrations (<-1 SDS), and 19 control children with normal stature (age 6.7 ± 0.3 years). We determined the levels of total and phosphorylated STAT3 in the cytoplasmic and nuclear fractions of fibroblast cultures obtained from a skin biopsy, stimulated with GH (200 ng/ml) for 15-60 min. RESULTS: We observed a reduction in nuclear pSTAT3 levels and a lower nuclear/cytoplasmic STAT3 phosphorylated ratio in 3 patients from the study group compared to the control children. CONCLUSION: These results suggest that some children with ISS may exhibit a reduction in the nuclear content of their phosphorylated STAT3.

The IGF-I response to growth hormone is related to body mass index in short children with normal weight.

AIM: We investigated whether the insulin-like growth factor (IGF)-I response to growth hormone (GH) is regulated by body mass index (BMI) in short children with normal weight. METHODS: We studied 37 prepubertal children with idiopathic short stature (ISS), comparing children with high-normal BMI (standard deviation scores, SDS 1.23 +/- 0.11, n = 20) and low-normal BMI (SDS -0.93 +/- 0.12, n = 17). The IGF-I response to GH was determined with an abbreviated IGF-I generation test, by measuring serum IGF-I concentrations at baseline and 24 h after the administration of GH (0.033 mg/kg). RESULTS: Children with high- and low-normal BMI had similar age (8.5 +/- 0.7 vs. 8.7 +/- 0.7 years) and height (-2.0 +/- 0.1 vs. -2.2 +/- 0.2 SDS). However, children with high-normal BMI exhibited higher mean basal IGF-I (191 +/- 15 vs. 139 +/- 11 ng/ml, p < 0.05), higher mean IGF-I levels 24 h after GH administration (261 +/- 22 vs. 164 +/- 14 ng/ml, p < 0.05) and a higher IGF-I percent increase after GH administration (37 +/- 5 vs. 17 +/- 4%, p < 0.05) compared with children with normal-low BMI. CONCLUSION: BMI modulates the IGF-I response to GH, suggesting that GH sensitivity may be influenced by the nutritional status in children with ISS and normal body weight.

Differences in body composition and energy expenditure in prepubertal children born term or preterm appropriate or small for gestational age.

Small size at birth may result from fetal undernutrition which may occur at different times during gestation. Early postnatal catch-up growth and excess childhood weight gain are associated with an increased risk of adult cardiovascular disease and type 2 diabetes mellitus. The aim of this study was to assess the relative contributions of body composition and energy expenditure on fasting insulin sensitivity during late childhood. We took advantage of two previously described prospective cohorts of children born either at term or prematurely, with a wide range of birth weights adjusted for gestational age. Seventy-one prepubertal children (mean age 7.5 +/- 0.3 years) were examined: 23 term SGA (8 M, 15 F), 12 preterm SGA (7 M, 5 F), 16 term AGA (8 M, 8 F), and 20 preterm AGA (9 M, 11 F). Mean height SDS was -0.18 +/- 0.11 and mean BMI SDS was 0.27 +/- 0.03. Change in weight SDS was significantly higher in children born SGA compared to their AGA counterparts (p < 0.001). Change in weight SDS was highly correlated with fasting insulin (p < 0.03) and leptin (p < 0.001). Fasting insulin correlated only with serum leptin levels. Body composition appeared to be the main determinant of fasting leptin levels. No differences in lipid profile were observed between the different groups. There was a clear tendency to higher insulin and leptin levels in children born SGA compared with their AGA counterparts. IGF-I levels were significantly higher only in SGA term compared to AGA term. Resting energy expenditure (REE) was lower in SGA born at term and higher in SGA born preterm compared to their AGA counterparts. In conclusion, fasting insulin sensitivity is mainly determined by leptin levels which in turn are determined by body composition. IGF-I and REE showed a divergent pattern in SGA term compared to SGA preterm groups. IGF-I levels were determined only by weight change from birth to age 2 years, which may not be as pronounced in VLBW children compared to SGA term and thus may preclude a difference in IGF-I levels in the group of preterm children. The divergent effect in REE in SGA born at term compared to SGA born preterm compared to their AGA counterparts may explain the divergent effects on IGF-I. This difference might be a consequence of different timing in the exposure to intrauterine nutritional deficiency.

Relationship between insulin sensitivity and IGF-I sensitivity in low birth weight prepubertal children.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and insulin are structurally related proteins with similar receptors and signal transduction systems. AIM: We postulate that some low birth weight (LBW) children may have decreased sensitivity to both insulin and IGF-I. METHODS: We studied 48 prepubertal LBW children aged 7.6 +/- 2.4 years. Insulin sensitivity was determined using an oral glucose tolerance test, and IGF-I sensitivity was assessed by determining nocturnal GH concentrations at baseline and after administration of recombinant human IGF-I/IGFBP-3 complex. RESULTS: Children were classified into quartiles of insulin sensitivity based on their glucose AUC/insulin AUC index. Children in the lowest quartile of insulin sensitivity exhibited a lower IGF-I sensitivity after administration of the rhIGF-I/rhIGFBP-3 complex compared to children in the highest quartile of insulin sensitivity (percent change in GH AUC: -44.2 +/- 5.7 vs. -21.6 +/- 6.8, p < 0.05). CONCLUSION: LBW children in the lowest quartile of insulin sensitivity exhibited a lower pituitary GH response to the administration of rhIGF-I/rhIGFBP-3. Our findings suggest that reduced sensitivity to insulin and IGF-I may coexist in some prepubertal LBW children.

Ala54Thr polymorphism of the fatty acid-binding protein 2 gene (intestinal-type FABP) is associated with changes in insulin sensitivity in SGA pubertal girls.

INTRODUCTION: Associations between FABP2 Ala54Thr polymorphism and increased fasting insulin concentration, fasting fatty acid oxidation and reduced glucose uptake have been identified in several populations. The aim of this study was to evaluate the association of Ala54 Thr polymorphism of the FABP2 gene with insulin sensitivity in pubertal girls born small for gestational age (SGA). RESULTS: The frequency of the Thr54 allele did not differ between AGA and SGA girls (0.52 vs 0.43). Girls born SGA positive for the Ala/Thr polymorphism were older at the beginning of puberty compared to girls born AGA with the Thr54 allele (p < 0.01). These girls had lower whole body insulin sensitivity index (WBISI) (4.1 +/- 1.7 vs 9.2+/-7.4, p < 0.05), higher leptin (17.3 +/- 5.9 vs 12.1 +/- 13.7, p < 0.02), insulin area under the curve (AUC) (64,272 +/- 9,209 vs 27,981 +/- 15,637, p < 0.001), proinsulin (17.3 +/- 5.4 vs 10.9 +/- 3.6, p < 0.01) and insulinogenic index (4.6 +/- 3.0 vs 2.9 +/- 5.9, p < 0.01). Conversely, girls born SGA positive for the Ala/Thr polymorphism were older at the beginning of puberty (ns) compared to girls born SGA positive for the Ala/Ala polymorphism. These girls had higher insulin AUC (64,272 +/- 9,209 vs 33,322 +/-7,533, p < 0.01), insulinogenic index (4.6 +/- 3.0 vs 2.5 +/- 3.6, p < 0.01) and lower WBISI (4.1 +/- 1.7 vs 6.3 +/- 1.8, p < 0.05). DISCUSSION: Our results suggest that the Thr54 variant of the FABP2 gene could be associated with a synergic effect in the SGA group regarding higher leptin levels (p < 0.05), lower insulin sensitivity by WBISI (p < 0.05) and higher insulin secretion determined by higher insulinogenic index (p < 0.01), insulin AUC (p < 0.01) and beta-cell stress measured by higher proinsulin (p < 0.05). Our data suggest an involvement of genetic factors in the insulin resistance associated with reduced fetal growth and strengthen the hypothesis that this association could be the consequence of interactions between detrimental factors during fetal life and genetic susceptibility.

E180splice mutation in the growth hormone receptor gene in a Chilean family with growth hormone insensitivity: a probable common Mediterranean ancestor.

Mutations in the GH receptor gene have been identified as the cause of growth hormone insensitivity syndrome (GHIS), a rare autosomal recessive disorder. We studied the clinical and biochemical characteristics and the coding sequence and intron-exon boundaries of the GH receptor gene in a consanguineous family with severe short stature which consisted of two patients, their parents and five siblings. The two adolescents had heights of -4.7 and -5.5 SDS, respectively, with elevated growth hormone associated with low IGF-I, IGFBP-3 and GHBP concentrations. Molecular analysis of the GH receptor gene revealed a mutation in exon 6, present in both patients This mutation, E180 splice, has been previously described in an Ecuadorian cohort, and in one Israeli and six Brazilian patients. We determined the GH receptor haplotypes based on six polymorphic sites in intron 9. Co-segregation of the E180splice mutation with haplotype I was found in this family, compatible with a common Mediterranean ancestor, as shown for previous cases with the E180splice mutation described to date.

Relationship between nocturnal growth hormone concentrations, serum IGF-I/IGFBP-3 levels, insulin sensitivity and GH receptor allelic variant in small for gestational age children.

Growth hormone may help to increase final height in patients with short stature, but its efficacy is variable. It has been recently reported that the isoform of the GH receptor (GHR) that lacks exon 3 (d3-GHR) is associated with a greater growth response to GH therapy. We hypothesized that nocturnal growth hormone concentrations, basal IGF-I and IGFBP-3 levels, and insulin sensitivity might show variations among individuals depending on their GHR allelic variant. To test this hypothesis, we studied 38 prepubertal LBW children with nocturnal GH concentrations, IGF-I and IGFBP-3 levels and insulin sensitivity during OGTT and Insulin test. The GHR allelic variant was analyzed through multiplex PCR analysis in DNA from peripheral leukocytes. Characteristics of the overnight GH secretion [(mean GH: 6.8 +/- 0.6 vs. 6.2 +/- 0.5 ng/ml), (AUC: 3,227 +/- 280 vs. 2,908 +/- 212 ng/ml.min), (peak number: 4.4 +/- 0.3 vs. 4.4 +/- 0.2), (amplitude: 12 +/- 1.1 vs. 10.8 +/- 1.1 ng/ml)] did not differ between groups (f1/f1 vs. f1/d3 plus d3/d3). In addition, we did not observe any significant differences in serum IGF-I SDS (-0.49 +/- 0.26 vs. -0.40 +/- 0.35) or IGFBP-3 SDS (-1.21 +/- 0.24 vs. -0.89 +/- 0.21) nor in insulin sensitivity (WIBSI: 12 +/- 1.2 vs. 10.8 +/- 1.1) in LBW children with full length GHR compared to children carrying at least one GHRd3 allele. The distribution of the f1/f1 allelic variant and fi/d3 or d3/d3 was similar in the LBW children with or without catch-up growth. These results suggest that the GHR allelic variant does not play a significant role in the regulation of GH-IGF-I/BP3 axis or in insulin sensitivity in prepubertal LBW children.

Effects of the IGF-I/IGFBP-3 complex on GH and ghrelin nocturnal concentrations in low birth weight children.

OBJECTIVE: There is limited information regarding the effects of IGF-I and/or IGFBP-3 on circulating ghrelin concentrations. To determine the effects of IGF-I on GH and ghrelin concentrations, we examined the GH and ghrelin nocturnal profiles before and after the administration of the IGF-I/-IGFBP-3 complex (Iplex) to low birth weight children. DESIGN: The children were studied on two separate occasions, the first under basal conditions, and the second time after the sc administration of 1 mg/kg of Iplex at 2100 h. Blood samples for determination of GH and ghrelin were obtained every 20 min between 2300 h and 0700 h, while the children were sleeping. In each patient, we calculated the mean GH and ghrelin area under the curve (GH AUC and GHR AUC), both under basal conditions and after the administration of the IGF-I/IGFBP-3 complex. SETTING: The study was performed at a University Research Centre located at a General Hospital in Santiago, Chile. PATIENTS: Twenty prepubertal children (11 boys and 9 girls), born after a full-term pregnancy with a birth weight below 2.8 kg were studied at a mean +/- SEM age of 7.3 +/- 0.5 years (range 4-11 years). Their mean height was -1.8 +/- 0.3 standard deviation score (SDS) and their mean BMI was 0.1 +/- 0.2 SDS at the time of the study. MAIN OUTCOME AND RESULTS: Mean nocturnal GH AUC exhibited a significant decrease (2903 +/- 185 vs 1860 +/- 122 ng/ml min, P < 0.01), whereas mean GHR AUC showed a significant increase after administration of the IGF-I/IGFBP-3 complex (68 +/- 16 vs 288 +/- 36 ng/ml min, P < 0.01). CONCLUSIONS: These findings indicate that the IGF-I/IGFBP-3 complex appears to have opposite effects on circulating GH and ghrelin concentrations in low birth weight children, suggesting that, in addition to its known negative feed-back effect on GH, IGF-I and/or IGFBP-3 may have a positive feed-back effect on ghrelin.

Longitudinal changes in insulin-like growth factor-I, insulin sensitivity, and secretion from birth to age three years in small-for-gestational-age children.

INTRODUCTION: Insulin resistance (IR) develops as early as age 1 to 3 yr in small for gestational age (SGA) infants who show rapid catch-up postnatal weight gain. In contrast, greater insulin secretion is related to infancy height gains. We hypothesized that IGF-I levels could be differentially related to gains in length and weight and also differentially related to IR and insulin secretion. METHODS: In a prospective study of 50 SGA (birth weight < 5th percentile) and 14 normal birth weight [appropriate for gestational age (AGA)] newborns, we measured serum IGF-I levels at birth, 1 yr, and 3 yr. IR (by homeostasis model assessment) and insulin secretion (by short iv glucose tolerance test) were also measured at 1 yr and 3 yr. RESULTS: SGA infants had similar mean length and weight at 3 yr compared with AGA infants. SGA infants had lower IGF-I levels at birth (P < 0.0001), but conversely they had higher IGF-I levels at 3 yr (P = 0.003) than AGA infants. Within the SGA group, at 1 yr IGF-I was associated with length gain from birth and insulin secretion (P < 0.0001); in contrast at 3 yr IGF-I was positively related to weight, body mass index, and IR. CONCLUSIONS: IGF-I levels increased rapidly from birth in SGA, but not AGA children. During the key first-year growth period, IGF-I levels were related to beta-cell function and longitudinal growth. In contrast, by 3 yr, when catch-up growth was completed, IGF-I levels were related to body mass index and IR, and these higher IGF-I levels in SGA infants might indicate the presence of relative IGF-I resistance.

Adiponectin levels in the first two years of life in a prospective cohort: relations with weight gain, leptin levels and insulin sensitivity.

Adiponectin, a novel adipocytokine with insulin sensitizing properties, is inversely related to obesity and insulin resistance in adults. We recently reported large variations in weight gain and insulin sensitivity during the first year in infants born small for gestational age (SGA) or appropriate for gestational age (AGA). We now determined whether adiponectin levels were related to postnatal growth and insulin sensitivity in a prospective cohort followed from birth to two years old (n = 85) (55 female/30 male, 65 SGA/20 AGA). Serum adiponectin levels at one year and two years were higher compared to reported levels in adults and older children, and decreased from one year (21.6 +/- 0.6 microg/ml) to two years (15.7 +/- 0.7 microg/ml) (p < 0.05). At two years adiponectin levels were lower in females (15.3 +/- 0.4 microg/ml) than males (16.4 +/- 0.6 microg/ml) (p < 0.05), but no gender difference was seen in leptin or insulin levels. No differences in adiponectin levels were seen between SGA and AGA infants at one or two years. However, in SGA infants changes in adiponectin between one to two years old were inversely related to weight gain (r = -0.310, p < 0.05). Changes in leptin levels between one to two years were positively related to weight gain in both SGA and AGA infants (r = 0.450 and r = 0.500 respectively, both p < 0.05). Adiponectin levels were unrelated to insulin levels at one or two years, nor to change in insulin levels between one to two years. In multiple regression analysis, adiponectin levels were related only to postnatal age; omitting age from the model, the determinants of higher adiponectin levels were male gender (p = 0.03), lower postnatal body weight (p < 0.001), and higher birth weight SD score (p = 0.004). In conclusion, fall in serum adiponectin levels during the first two years of life were related to increasing age and greater weight gain SGA infants, but were unrelated to insulin sensitivity.

Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort.

Strong associations between low birth weight and insulin resistance have been described. However, most of these studies have been retrospective. We aimed to determine whether infants born small for gestational age (SGA: birth weight <5th percentile for gestational age) have decreased insulin sensitivity, compared with appropriate for gestational age (AGA: birth weight >10th percentile) at 1 yr of age. We studied blood lipids, fasting insulin levels, other markers of insulin sensitivity, and insulin secretion during an iv glucose tolerance test in a cohort of 85 SGA and 23 AGA 1-yr-old infants. In addition, SGA infants were stratified according to catch-up growth (CUG) in weight (WCUG) or length (LCUG) during the first year of life. At 1 yr, SGA infants had a clear tendency to higher triglycerides. Fasting insulin was significantly higher in SGA infants with WCUG, compared with those who did not catch up and AGA infants (mean +/- SEM, 32.6 +/- 4.6 vs. 14.9 +/- 2.3 vs. 21.4 +/- 3.3 pM, respectively; P < 0.05). Length increment (in SD score) was the principal determinant of postload insulin secretion (R(2) = 0.1, P < 0.01). We conclude that insulin secretion and sensitivity are closely linked to patterns of rapid WCUG and LCUG during early postnatal life. Fasting insulin sensitivity is more related to WCUG and current body mass index, whereas insulin secretion seems to be directly related to LCUG.