Teresa Salazar

University of Santiago, Chile, CiudadSantiago, Santiago, Chile

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Publications (32)86.9 Total impact

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    ABSTRACT: Abstract 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.
    Journal of pediatric endocrinology & metabolism: JPEM 01/2013; · 0.75 Impact Factor
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    ABSTRACT: The biochemical mediators responsible for variations in stature among normal subjects are largely unknown. To obtain some initial information about potential endocrine factors, we measured the serum concentrations of GH, IGF-1, IGFBP-3 and GHBP in healthy young men shorter than 159 cm and taller than 187 cm. We studied 14 volleyball and basketball players (tall group), and 14 jockey students from a horse racetrack (short group). A careful medical history was taken, including dietary intake, and physical examination with special attention to the possible presence of genetic stigmata was performed. Serum prealbumin was determined as an index of nutritional status. A buccal smear was performed to exclude Klinefelter's syndrome. The BMI and serum prealbumin levels were comparable in both groups of individuals. The nutritional survey, however, revealed that the tall subjects had a higher intake of calories (42.2+/-11.2 vs. 30.1+/-15.15 kcal/kg, p<0.05), and protein (1.5+/-0.6 vs. 0.8+/-0.4 mg/kg, p<0.01). Serum concentrations of GHBP did not differ in the two groups (0.95+/-0.37 nmol/l in the tall, and 0.95+/-0.53 nmol/l in the short group), and did not correlate with height, serum IGF-I levels, or BMI. We observed a significant difference in the serum concentrations of IGF-I in the two groups of individuals (42.02+/-9.37 nmol/l in the tall and 31.79+/-3.18 nmol/l in the short group, p<0.05), and this growth factor showed a positive correlation with height (r = 0.5, p<0.01). These preliminary findings suggest that final height differences in young men do not appear to be mediated by variations in GHBP concentrations.
    Journal of pediatric endocrinology & metabolism: JPEM 01/2011; 13(7):887-92. · 0.75 Impact Factor
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    ABSTRACT: 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. We determined total and phosphorylated STAT3 after GH stimulation in fibroblasts from children with idiopathic short stature (ISS) and control children with normal stature. We studied 15 prepubertal children (age 7.6 ± 0.4 years) with short stature (height -2.8 ± 0.2 SDS), decreased growth velocity (<p10), a GH response of >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. 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. These results suggest that some children with ISS may exhibit a reduction in the nuclear content of their phosphorylated STAT3.
    Hormone Research in Paediatrics 01/2010; 74(4):251-8. · 1.55 Impact Factor
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    ABSTRACT: 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.
    Journal of pediatric endocrinology & metabolism: JPEM 11/2009; 22(11):1041-50. · 0.75 Impact Factor
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    ABSTRACT: To assess normative data and the usefulness of spontaneous and LHRH analogue-stimulated serum LH and FSH levels measured by immunoradiometric assays (IRMA) in the evaluation of normal puberty. Prospective. Healthy girls in Tanner I and Tanner II from the local community were invited to participate (n = 47). A leuprolide acetate test (500 mcg/m(2); sc) was performed. LH and FSH levels were determined using IRMA. Tanner II girls were assessed every 6 months until Tanner V. Girls who progressed from Tanner II to Tanner III in the next 6 months were called Tanner II-2; otherwise, they were called Tanner II-1. The prepubertal upper limit (CI 95%) was 0.49 IU/l for basal LH and 5.1 IU/l for stimulated LH. Taking into account these LH cut-off limits, 72.2% and 66.7% of Tanner II-1 and 41.6% and 41.7% of Tanner II-2 subjects presented overlapping values for basal and stimulated LH, respectively, as compared with the Tanner I group. The cut-offs for basal and stimulated LH to predict progression from Tanner II to Tanner III in the next 6 months were a basal LH level > or =0.49 IU/l (Sensitivity = 0.58; 1-Specificity = 0.33) and a poststimulated LH level > or =4.75 IU/l (Sensitivity = 0.67; 1-Specificity = 0.44). According to an IRMA, the basal and leuprolide acetate gonadotrophin response patterns during the beginning stages of puberty overlapped between Tanner I and Tanner II, and the cut-offs of basal and stimulated LH levels to predict progress from Tanner II to Tanner III had low sensitivities for the following 6 months.
    Clinical Endocrinology 10/2009; 72(4):489-95. · 3.40 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    Hormone Research 02/2009; 72(1):10-4. · 2.48 Impact Factor
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    ABSTRACT: 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.
    Journal of pediatric endocrinology & metabolism: JPEM 01/2009; 21(12):1119-27. · 0.75 Impact Factor
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    ABSTRACT: 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. 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. 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). 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.
    Hormone Research 06/2008; 70(2):73-8. · 2.48 Impact Factor
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    ABSTRACT: 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). 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). 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.
    Journal of pediatric endocrinology & metabolism: JPEM 02/2008; 21(2):117-25. · 0.75 Impact Factor
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    ABSTRACT: Small for gestational age (SGA) has been associated with decreased insulin sensitivity (IS). A possible mechanism is the postnatal development of a metabolically disadvantageous body composition (BC). To determine whether there are differences between IS and BC in girls in early puberty who were SGA (birth weight < 10th percentile) or appropriate for gestational age (AGA, 10th-90th percentile). Age-matched (SGA/AGA) early pubertal girls (Tanner II) were recruited from local schools. We determined waist circumference (WC), the sum of four skinfolds (S4S), and per cent fat mass (fat %) by impedanciometry. Leptin and OGTT assays were performed. The insulinogenic index (I-In), HOMA-IR (homeostasis model assessment of insulin resistance) and WBISI (whole body insulin sensitivity) were calculated. Median age (interquartile range) for 30 SGA and 35 AGA girls was 10.2 (1.1) vs. 9.8 (0.9), respectively (P = NS). BMI percentiles were 62.6 (56) vs. 67.4 (39); WC 60.5 (9.5) vs. 62.2 (6.5) cm; S4S 52 (30) vs. 52.2 (29.5) cm, and fat %[26.2 (6.7) vs. 28.5 (6.3)] was similar in both groups. SGA girls had higher leptin levels [15.4 (9.7) vs. 9.6 (11) ng/ml; P = 0.01] and I-In [2.05 (1.86) vs. 1.47 (1.27) microU/ml* mg/dl; P = 0.02]. No differences between HOMA-IR [2.07 (1.26) vs. 2.04 (1.4)] and WBISI [5.3 (3.3) vs. 5.1 (3.1)] were found between groups. The higher leptin level and I-In in girls born SGA at the beginning of puberty may be early indicators of an underlying subtle degree of insulin resistance, despite similar BMI and BC to AGA girls.
    Clinical Endocrinology 10/2007; 67(4):526-32. · 3.40 Impact Factor
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    ABSTRACT: 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.
    Hormone Research 02/2007; 68(3):132-8. · 2.48 Impact Factor
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    ABSTRACT: 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. 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. The study was performed at a University Research Centre located at a General Hospital in Santiago, Chile. 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. 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). 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.
    Clinical Endocrinology 12/2006; 65(5):687-92. · 3.40 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Journal of Clinical Endocrinology &amp Metabolism 11/2006; 91(11):4645-9. · 6.43 Impact Factor
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    ABSTRACT: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.
    Journal of Clinical Endocrinology &amp Metabolism 10/2006; 91(9):3377-81. · 6.43 Impact Factor
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    ABSTRACT: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestational-age (SGA) at birth may be a consequence of rapid early postnatal weight gain. We prospectively studied early changes in fasting insulin sensitivity and insulin secretion, assessed by a short intravenous glucose tolerance test that was conducted several times from birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns and in 13 newborns with a birthweight appropriate for gestational age (AGA). Most SGA infants showed postnatal upward weight centile crossing and by 3 years were similar in size to AGA infants. SGA infants had lower pre-feed insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7 pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not differ between SGA and AGA infants, but SGA infants had a lower glucose disposition index (beta cell compensation) (median 235 vs 501 min mmol(-1) l(-1), p=0.02), which persisted after allowing for postnatal weight gain (p=0.009). SGA infants showed a marked transition from lower pre-feed insulin and increased insulin sensitivity at birth to insulin resistance over the first 3 years of life. This transition was related to rapid postnatal weight gain, which could indicate a propensity to central fat deposition. The additional observation of reduced compensatory beta cell secretion underlines the need for long-term surveillance of glucose homeostasis in all SGA subjects, whether or not they show postnatal catch-up growth.
    Diabetologia 01/2006; 48(12):2609-14. · 6.49 Impact Factor
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    ABSTRACT: 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.
    Journal of Clinical Endocrinology &amp Metabolism 12/2004; 89(11):5500-3. · 6.43 Impact Factor
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    ABSTRACT: 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.
    Journal of Clinical Endocrinology &amp Metabolism 08/2003; 88(8):3645-50. · 6.43 Impact Factor
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    ABSTRACT: To study the consequences of low birth weight on glucose and lipid metabolism 48 hours after delivery. We studied 136 small for gestational age (SGA) and 34 appropriate for gestational age (AGA) term neonates who were born in Santiago, Chile. Prefeeding venous blood was obtained 48 hours after birth for determination of glucose, free fatty acids, beta-hydroxy butyrate, insulin, C-peptide, leptin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 (IGFBP-1), and cortisol. SGA newborns had lower glucose (SGA versus AGA, median [interquartile range]: 3.6 mmol/L [2.9-4.1 mmol/L] vs 3.9 mmol/L [3.6-4.6 mmol/L]) and insulin levels (31.3 pmol/L [20.8-47.9 pmol/L] vs 62.5 pmol/L [53.5-154.9]) than AGA infants, and they had higher glucose/insulin ratios (13.9 mg/dL/uIU/mL [8.6-19.1 mg/dL/uIU/mL] vs 8.2 mg/dL/uIU/mL [4.6-14.1 mg/dL/uIU/mL]). SGA infants also had higher levels of IGFBP-1 (5.1 nmol/L [4.4-6.7 nmol/L] vs 2.9 nmol/l [1.4-4.2 nmol/L]), free fatty acids (0.72 mEq/L [0.43-1.00 mEq/L] vs 0.33 mEq/L [0.26-0.54 mEq/L]) and beta-hydroxy butyrate (0.41 mEq/L [0.15-0.91 mEq/L] vs 0.09 mEq/L [0.05-0.13 mEq/L]). Sex-hormone binding globulin levels were not significantly different between the 2 groups. In early postnatal life, SGA infants display an increased insulin sensitivity with respect to glucose disposal but not with respect to suppression of lipolysis, ketogenesis, and hepatic production of IGFBP-1. It will be important to determine how these differential sensitivities to insulin vary with increasing age.
    PEDIATRICS 05/2003; 111(4 Pt 1):804-9. · 4.47 Impact Factor
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    ABSTRACT: We hypothesized that some children with idiopathic short stature in Chile might bear heterozygous mutations of the GH receptor. We selected 26 patients (3 females, 23 males) from 112 patients who consulted for idiopathic short stature at the University of Chile. Their chronological age was 8.3 +/- 1.9, and bone age was 6.1 +/- 1.0 yr. Their height was -3.0 +/- 0.7 SDS; IGF-I, -1.2 +/- 1.1 SD; IGF binding protein 3, -0.7 +/- 2.0 SDS; and GH binding protein, 0.4 +/- 0.8 SDS. Patients were admitted, and blood samples were obtained every 20 min to determine GH concentrations overnight. Coding sequences and intron-exon boundaries of exons 2-10 of GH receptor gene were amplified by PCR and subsequently analyzed through single-strand conformational analysis. Mean serum GH concentration, over 12-h, was 0.20 +/- 0.08 nM; pulse amplitude, 0.40 +/- 0.15 nM; number of peaks, 5.8 +/-1.5 peaks/12 h; peak value of GH during the 12-h sampling, 1.03 +/- 0.53 nM; and area under the curve, 151.4 +/- 56.1 nM/12 h. There were positive correlations between mean GH vs. area under the curve (P < 0.001) and GH peak (P < 0.01). The single-strand conformational analysis of the GH receptor gene showed abnormal migration for exon 6 in 9 patients and for exon 10 in 9 patients, which (by sequence analysis) corresponded to 2 polymorphisms of the GH receptor gene: an A-to-G transition in third position of codon 168 in exon 6 and a C-to-A transversion in the first position of codon 526 in exon 10. We further sequenced all coding exons and intron-exon boundaries in the most affected patients (nos. 6, 9, 11, 14, 15, 16, and 23). This analysis revealed a C-to-T transition in codon 161 of exon 6 in patient 23, which results in an amino acid change (Arg to Cys) in an heterozygous form in the patient and his father. In conclusion, the results of our study suggest that, in Chilean patients with idiopathic short stature, GH receptor gene mutations are uncommon, although we cannot exclude mutations that were missed by single-strand conformational analysis or mutations within introns or in the promoter regions of the GH receptor gene.
    Journal of Clinical Endocrinology &amp Metabolism 10/2001; 86(9):4375-81. · 6.43 Impact Factor
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    ABSTRACT: Circulating concentrations of the high affinity growth hormone binding protein (GHBP) may be a marker of GH receptor density as well as GH sensitivity. To determine values of GHBP for a normal Chilean pediatric population. We determined GHBP levels in 73 males and 73 females between 4 to 15.5 years and 4 to 16.8 years respectively, divided in 7 groups according to age and puberal status. The population was normally distributed in weight, height and body mass index (BMI). GHBP activity increased up to Tanner IV in males and Tanner III in females, and decreased slightly thereafter in Tanner V and IV respectively. There was a significant difference between GHBP levels of preschool children and those found in Tanner II to V in both sexes (p < 0.05). In addition, we found a positive correlation between GHBP vs weight, height and BMI (p < 0.001) in males and females. The availability of this methodology allows us to establish the normative value of GHBP in our population and provides useful information to interpret GH circulating levels in children with growth disorders.
    Revista medica de Chile 04/2001; 129(4):382-9. · 0.36 Impact Factor