RESUMO
Previously, we demonstrated decreased protein breakdown and insulin resistance in pubertal adolescents compared with prepubertal children. Puberty-related increases in sex steroids and/or GH could be potentially responsible. In the present study, the effects of 4 months of testosterone enanthate (50 mg in every 2 weeks) on body composition, protein, fat, and glucose metabolism and insulin sensitivity were evaluated in adolescents with delayed puberty. Body composition was assessed by H218O-dilution principle. Protein breakdown, oxidation, and synthesis were measured during primed constant infusion of [1-13C]leucine. Whole-body lipolysis was measured during primed constant infusion of [2H5]glycerol. Insulin action in suppressing proteolysis and lipolysis and stimulating glucose disposal was assessed during a stepwise hyperinsulinemic (10 and 40 mU-m2.min) euglycemic clamp. Fat and glucose oxidation rates were calculated from indirect calorimetry measurements. After 4 months of testosterone treatment, height, weight, and fat free mass (FFM) increased and fat mass, percent body fat, plasma cholesterol, high- and low-density lipoproteins, and leptin levels decreased significantly. Whole-body proteolysis and protein oxidation were lower after testosterone treatment (proteolysis, 0.49 +/- 0.03 vs 0.54 +/- 0.04 g.h.kg FFM, P = 0.032; oxidation, 0.05 +/- 0.01 vs. 0.09 +/- 0.01 g.h.kg FFM, P = 0.015). Protein synthesis was not different, and resting energy expenditure was not different. Total body lipolysis was not affected by testosterone treatment, however, fat oxidation was higher after testosterone (pre-: 2.4 +/- 0.7 vs. post-: 3.5 +/- 0.7 mumol.kg.min, P = 0.031). During the 40 mU.m2.min hyperinsulinemia, insulin sensitivity of glucose metabolism was not affected with testosterone therapy (59.1 +/- 8.8 vs. 57.1 +/- 8.2 mumol.kg.min per muU/mL). However, metabolic clearance rate of insulin was higher posttestosterone (13.6 +/- 1.1 vs. 16.7 +/- 0.8 mL.kg.min, P = 0.004). In conclusion, after 4 months of low-dose testosterone treatment in adolescents with delayed puberty 1) FFM increases and fat mass and leptin levels decrease; 2) postabsorptive proteolysis and protein oxidation decrease; 3) fat oxidation increases; and 4) insulin sensitivity in glucose metabolism does not change, whereas insulin clearance increases. These longitudinal observations are in agreement with our previous cross-sectional studies of puberty and demonstrate sparing of protein breakdown of approximately 1.2 g.kg.day FFM, wasting of fat mass, but no change in insulin sensitivity after short periods of low-dose testosterone supplementation.
Assuntos
Composição Corporal/efeitos dos fármacos , Puberdade Tardia/tratamento farmacológico , Puberdade Tardia/metabolismo , Testosterona/uso terapêutico , Adolescente , Gorduras/metabolismo , Glucose/metabolismo , Humanos , Hiperinsulinismo/metabolismo , Estudos Longitudinais , Masculino , Oxirredução/efeitos dos fármacos , Proteínas/metabolismo , Puberdade Tardia/patologiaRESUMO
Syndrome X, or the syndrome of insulin resistance, is a cluster of related metabolic abnormalities of hyperinsulinemia, glucose intolerance, increased very low density lipoprotein (VLDL), decreased high density lipoprotein (HDL), and hypertension in nonobese adults and plays an important role in the genesis of cardiovascular disease. The aim of the present study was to examine the relationships among insulin sensitivity, plasma lipid levels, and body composition in the pediatric age group to determine whether these associations are present in childhood. Twenty healthy Caucasian Tanner stage I (TI) children (age, 10.7 +/- 0.3 yr; body mass index, 18.9 +/- 0.8 kg/m2) and 22 pubertal Tanner stage II-IV (TII-IV) adolescents (age, 14.0 +/- 0.3 yr; body mass index, 20.0 +/- 0.4 kg/m2) were studied. In vivo insulin-mediated glucose disposal (Rd) was evaluated during a 40 mu/m2. min hyperinsulinemic-euglycemic clamp. Body composition was assessed isotopically by the H218O dilution principle. Fasting blood was obtained for cholesterol, triglyceride (TG), VLDL, low density lipoprotein (LDL), and HDL determinations. In both groups, the strongest correlation of Rd was with percent body fat (%BF) (TI: r = -0.82; P < 0.001; TII-IV: r = -0.73; P < 0.001). In addition, in TI, Rd was correlated with TG (r = 0.64; P = 0.001), VLDL (r = 0.64; P = 0.001), and diastolic blood pressure (r = -0.50; P = 0.01). There were no such correlations in TII-IV. In TI, % BF correlated positively with LDL and negatively with TG and VLDL. In TII-IV, % BF correlated positively with cholesterol and LDL. After correcting for %BF, partial correlation analysis revealed no relationship between Rd and lipid levels in either group. This suggests that the relationship of insulin sensitivity to lipid levels was secondary to the effect of body composition on lipid levels. However, regardless of body composition, the basal insulin level was correlated with TG (r = 0.38; P = 0.04) and VLDL (r = 0.40; P = 0.04) in TII-IV subjects. We conclude that 1) the primary correlate of insulin sensitivity is %BF in both prepubertal and pubertal subjects, with no relationship to plasma lipids; 2) in prepubertal children, diastolic blood pressure is negatively correlated with insulin sensitivity and positively with insulin levels, independent of adiposity; and 3) after the onset of puberty, basal insulin levels are positively correlated with VLDL and TG regardless of the degree of adiposity. This observation could be a very early manifestation of the genesis of syndrome X in childhood.
Assuntos
Composição Corporal , Resistência à Insulina , Insulina/fisiologia , Lipídeos/sangue , Tecido Adiposo/patologia , Adolescente , Criança , Glucose/metabolismo , Humanos , Puberdade/fisiologiaRESUMO
We had previously demonstrated greater insulin secretion and lower insulin sensitivity in black pubertal adolescents compared with whites. This study aimed to investigate whether similar black/white differences are present in the prepubertal period or are characteristics of the pubertal period. Twelve black and 11 white healthy prepubertal children, matched for age, body mass index, and Tanner I pubertal development, underwent a 2-h hyperglycemic clamp (225 mg/dL). Physical fitness was assessed by maximal oxygen consumption (VO2max) measurement during graded bicycle ergometry, and resting energy expenditure was measured by indirect calorimetry after overnight fast. Fasting and first phase insulin concentrations were higher in blacks than in whites [14.7 +/- 1.3 vs. 10.4 +/- 1.2 (P = 0.02) and 76.9 +/- 6.8 vs. 52.1 +/- 6.4 microU/mL (P = 0.016)]. There were no differences in second phase insulin levels and insulin sensitivity index. Both maximal oxygen consumption (VO2max) and resting energy expenditure were lower in black children, whereas insulin-like growth factor I was higher. After controlling for these differences, race contributed significantly to basal insulin, but not to first phase insulin. In summary, previously reported black/white differences in insulin secretion and sensitivity during adolescence may have their origin in early childhood manifested as hyperinsulinemia. However, genetic (race) vs. environmental factors (physical activity/fitness and energy balance) should be carefully scrutinized as potential factors responsible for such differences.
Assuntos
População Negra , Resistência à Insulina , Insulina/metabolismo , Puberdade , População Branca , Glicemia/análise , Criança , Feminino , Técnica Clamp de Glucose , Humanos , Insulina/sangue , Secreção de Insulina , Masculino , Concentração Osmolar , Valores de Referência , Análise de Regressão , Caracteres SexuaisRESUMO
Leptin has been demonstrated to reflect body fat mass (FM) in humans, but the regulation of leptin levels during childhood growth and development is poorly understood. We studied the relation between plasma leptin, fasting insulin, insulin sensitivity, and resting energy expenditure in 22 healthy prepubertal children and 27 adolescents. Body composition was assessed by the H2(18)O-dilution principle, insulin sensitivity by a hyperinsulinemic (40 mU/m2/min)-euglycemic clamp, and energy expenditure by indirect calorimetry. Plasma leptin in prepubertal children (9.3 +/- 2.0 ng/mL) was not different from that in pubertal adolescents (10.9 +/- 2.2 ng/mL). Plasma leptin correlated with FM (r = .77, P < .001). There were no gender differences in leptin after controlling for FM differences. In prepubertal and pubertal subjects, plasma leptin correlated with fasting insulin independently of FM (r = .60, P < .001), but did not correlate with insulin sensitivity independently of body fat content. Leptin showed no relationship to resting energy expenditure after adjusting for body composition. The present cross-sectional evaluation of normal children shows that (1) plasma leptin reflects body fat content, (2) leptin concentrations are similar between prepubertal children and pubertal adolescents, (3) there are no gender differences in leptin independent of adiposity, and (4) leptin correlates with fasting insulin but not with insulin sensitivity. Contrary to animal data, our cross-sectional results in healthy children do not suggest a role for leptin in puberty or a female-related leptin resistance as reported in adults. It remains to be determined at which stage of human development the sexual dimorphism in leptin becomes evident.
Assuntos
Composição Corporal , Metabolismo Energético , Insulina/farmacologia , Proteínas/metabolismo , Puberdade/fisiologia , Caracteres Sexuais , Adolescente , Glicemia/metabolismo , Criança , Feminino , Humanos , Insulina/sangue , Leptina , Masculino , Oxirredução , Valores de ReferênciaRESUMO
An outbreak of neonatal infection with Salmonella urbana in three neonatal wards of a teaching hospital in Bangkok, Thailand is described. The outbreak lasted for 5 days. Fifty-seven neonates had gastrointestinal infection, 37 had diarrhoea, and three had bacteraemia. The attack rates were 43% for infection, 29% for diarrhoea, and 2.3% for bacteraemia. Epidemiological evaluation suggested that a contaminated wash basin in the labour nursery was the source of infection. Delay in controlling this outbreak occurred because the staff assumed that person-to-person transmission was the mode of spread, thus ignoring epidemiological data that would have led to the identification of the source of infection.
Assuntos
Infecção Hospitalar/epidemiologia , Surtos de Doenças , Gastroenteropatias/epidemiologia , Berçários Hospitalares/normas , Infecções por Salmonella/epidemiologia , Sepse/epidemiologia , Infecção Hospitalar/etiologia , Infecção Hospitalar/prevenção & controle , Gastroenteropatias/etiologia , Gastroenteropatias/prevenção & controle , Hospitais de Ensino/normas , Humanos , Incidência , Recém-Nascido , Infecções por Salmonella/etiologia , Infecções por Salmonella/prevenção & controle , Engenharia Sanitária/normas , Sepse/etiologia , Sepse/prevenção & controle , Tailândia/epidemiologiaRESUMO
The determination of body composition as part of the clinical and auxologic follow up of childhood growth disorders necessitates the use of a quick, portable, reliable and simple non-invasive method. The present study was undertaken to validate bioelectrical conductance, height2/resistance (Ht2/R), against isotopically determined total body water (TBW) using heavy water tracer H2[18O]. The subjects (n = 56) consisted of normal children, children with various endocrine disorders, and young adults between the ages of 8-26 years. Isotopically determined TBW and fat free mass (FFM) were highly correlated with Ht2/R (r = 0.94, p = < 0.001, and r = 0.94, p = < 0.001, respectively). In a multiple regression analysis, 96% of the variability in FFM in normal subjects could be predicted by the following equation: FFM = 0.524 Ht2/R + 0.415 Wt-0.32, while in the group of patients by FFM = 0.659 Ht2/R + 0.254 Wt + 2.851. These data suggest that bioelectrical impedance measurements give valid and reliable estimates of FFM in children and adolescents. This easy technique could be incorporated in the auxologic follow up of children on hormone therapy.
Assuntos
Composição Corporal , Impedância Elétrica , Técnicas de Diluição do Indicador , Adolescente , Adulto , Estatura , Água Corporal , Criança , Feminino , Hormônio do Crescimento/deficiência , Humanos , Masculino , Síndrome do Ovário Policístico , Puberdade , Puberdade Tardia , Análise de RegressãoRESUMO
BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of persistent hypoglycemia in infants. The current standard treatment is subtotal pancreatectomy (Px). However, the long-term outcome following surgery needs further attention. METHODS: We analyzed 10 children (7 M, 3 F) with PHHI who underwent partial (65-80%) and subtotal (81-95%) Px. Follow-up ranged from 2 to 9.4 yr (mean = 4.2 yr). We divided them into 2 groups based upon the age at onset of hypoglycemia: early (< 1 mo) and late (> or = 1 mo). RESULTS: The seven patients in the early-onset group underwent 85-95% Px between ages of 18 d and 3 mo. Three of them initially treated by 85-90% Px had persistent hypoglycemia postoperatively. Two out of three required a 2nd operation with 95% Px for controlling hypoglycemia, though both still had persistent hypoglycemia and required medication to control blood glucose. The remaining four had 95% Px and had maintained euglycemia postoperatively. One patient developed diabetes 6 yr after surgery. Six of seven patients had delayed development and subnormal IQ. Three patients of the late-onset group (3 mo, 6 mo and 4 yr) underwent partial Px (80%, 65% and 65%, respectively) and maintained euglycemia postoperatively. Despite 65% Px, one developed diabetes 3 yr after surgery. CONCLUSIONS: These results suggest that children with early-onset hypoglycemia have more severe hyperinsulinism than those with late-onset hypoglycemia. The former require 95% Px for maintaining euglycemia, but long-term complications with diabetes may be common. In contrast, the latter require lower percentage Px which may reduce the incidence of diabetes in the future.
Assuntos
Hiperinsulinismo/complicações , Hiperinsulinismo/cirurgia , Hipoglicemia/complicações , Hipoglicemia/cirurgia , Pancreatectomia , Resultado do Tratamento , Fatores Etários , Glicemia/metabolismo , Diabetes Mellitus/etiologia , Feminino , Glucose/administração & dosagem , Teste de Tolerância a Glucose , Transtornos do Crescimento/etiologia , Humanos , Hipoglicemia/tratamento farmacológico , Lactente , Recém-Nascido , Insulina/sangue , Deficiência Intelectual/etiologia , Masculino , Reoperação , Estudos RetrospectivosRESUMO
Leptin, the protein product of the obesity gene, produced by adipose tissue, regulates body weight and energy expenditure through CNS feedback mechanisms. In obesity, leptin levels are elevated suggestive of leptin resistance. Because of increased prevalence of obesity in African-Americans, the aim of this study was to assess leptin and its relationship to adiposity in African-American children. We measured plasma leptin levels in 42 African-American children (23 M, 19 F), age 11.8 +/- 0.3 yr, and compared them with 30 American-White children matched for age, body composition and puberty. Body composition was assessed by bioelectrical impedance and plasma leptin by RIA. Data are presented as means +/- SEM and statistical significance is implied by p < 0.05. There was no racial difference in plasma leptin levels (Blacks: 9.8 +/- 1.6, Whites 9.8 +/- 1.9 ng/ml). Leptin correlated with %BF in Black (r = 0.75, p = 0.005) and White (r = 0.79, p = 0.005) children. There were no gender or puberty related differences in leptin levels in African-American children. We concluded that leptin levels are comparable between African-American and American White children of similar body composition. The major determinant of serum leptin levels in these children is degree of adiposity with no gender or puberty related differences. Longitudinal studies are needed to assess leptin's role during puberty in both genders.
Assuntos
Leptina/sangue , População Negra , Composição Corporal/fisiologia , Criança , Métodos Epidemiológicos , Jejum/metabolismo , Feminino , Humanos , Lipídeos/sangue , Masculino , Valores de Referência , Caracteres Sexuais , Aumento de Peso/fisiologia , População BrancaRESUMO
This study reports the result of treatment with the combination of raw cornstarch and nifedipine in two infants affected with hyperinsulinemic hypoglycemia of variable severity. The first infant developed hypoglycemia during early neonatal period and required subtotal pancreatectomy. She still developed hypoglycemia after her second operation. The second infant developed hypoglycemia at the age of 7 months. Raw cornstarch and nifedipine efficiently normalized both infants' blood glucose levels. Although they still need frequent feedings, no hypoglycemic episode was reported except when they were sick. Their growth and development were markedly improved after initiation of treatment.
Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Nifedipino/uso terapêutico , Pancreatopatias/tratamento farmacológico , Amido/uso terapêutico , Quimioterapia Combinada , Humanos , Lactente , Recém-NascidoRESUMO
The patient was the first child of a short mother (140 cm) born at term with a birthweight of 2,700 g. On arrival, she was 1 4/12-year-old, weighed 4,150 g and 47 cm long. Her bone age was at the 6 month-old level. Endocrine investigation revealed undetectable plasma growth hormone (GH), thyrotropin (TSH) and prolactin (PRL) levels. CT scan of ovaries revealed bilateral ovarian agenesis in spite of normal, 46 XX karyotype. MRI of the brain did not demonstrate intracranial tumor or congenital malformation. Peak plasma GH level after oral clonidine provocation, insulin induced hypoglycemia, and I.V. GH-RF stimulation were 0.6, 0, and 0 ng/ml respectively. Peak plasma TSH response after I.V. TRH stimulation was 0.04 microU/ml. The patient could not secrete PRL at any time after insulin induced hypoglycemia, TRH and metoclopramide stimulations. On the other hand the child had elevated basal plasma cortisol (38 micrograms/dl at 8.00 AM) and raised 24 hr urinary 17 OHCS excretion (50 mg/1 g Cr against normal value of 3 mg/1 g Cr) without evidence of Cushing syndrome probably indicate partial glucocorticoid resistance. Peak plasma cortisol responses after intravenous metoclopramide and insulin induced hypoglycemia were 46 and 42.9 micrograms/dl respectively. Dexamethasone administration reduced plasma cortisol to 2.9 micrograms/dl. The child had also elevated basal plasma FSH (36 microU/ml) and LH (5 microU/ml) with further elevation to the peak of 123 and 99 microU/ml respectively after LHRH stimulation. All evidence suggested the diagnosis of congenital complete absence of GH, TSH, and PRL which is characteristic of Pit-1-gene deletion.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doenças do Sistema Endócrino/genética , Deleção de Genes , Hormônio do Crescimento/deficiência , Prolactina/deficiência , Tireotropina/deficiência , Proteínas de Ligação a DNA , Feminino , Humanos , Lactente , Fator de Transcrição Pit-1 , Fatores de TranscriçãoRESUMO
Fourteen black and 16 white healthy adolescents underwent a 2-hour hyperglycemic clamp (12.5 mmol/L) to investigate racial differences in insulin secretion and sensitivity. First-phase and second-phase insulin concentrations were higher in black subjects than in white subjects (first phase: 944 +/- 110 pmol/L vs. 462 +/- 52 pmol/L, p = 0.0003; second phase: 1050 +/- 146 pmol/L vs. 652 +/- 53 pmol/L, p = 0.0012). The insulin sensitivity index was lower in black adolescents (8.21 +/- 1.05) compared with white adolescents (12.55 +/- 1.42 mumol/kg per minute per picomole per liter, p = 0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable in healthy black versus white adolescents.
Assuntos
População Negra , Resistência à Insulina , Insulina/metabolismo , População Branca , Adolescente , Glicemia , Criança , Técnica Clamp de Glucose , Humanos , Secreção de Insulina , Valores de ReferênciaRESUMO
This investigation examined whether puberty differs from prepuberty in regard to the effects of increased free fatty acid (FFA) on in vivo glucose metabolism. Nine prepubertal and 13 pubertal healthy children were studied. Each subject was studied twice, once with 0.9% sodium chloride solution (control study) and once with 20% Intralipid infusion in the basal state and during a 3-h hyperinsulinemic-euglycemic clamp, with [6,6-2H2]glucose tracer. During control studies, prepubertal children had lower basal fat oxidation and higher insulin-mediated glucose disposal than pubertal adolescents. During Intralipid infusion, basal glucose uptake increased in prepubertal children but did not change in pubertal adolescents. Insulin-stimulated whole body glucose disposal did not change in prepubertal children (control 77.6 +/- 8.9, Intralipid 84.5 +/- 13.3 micromol x kg(-1) x min(-1)) but decreased in pubertal adolescents (control 55.0 +/- 3.6, Intralipid 46.7 +/- 3.4 micromol x kg(-1) x min(-1), P = 0.01) despite comparable decrements in glucose oxidaion. We conclude that in prepubertal children lipids exert effects in the basal state by stimulating hepatic glucose production and glucose disposal, whereas in pubertal adolescents they induce peripheral tissue insulin resistance by decreasing insulin-stimulated glucose uptake. This differential response could be due to developmental-maturational changes in tissue sensitivity and/or specificity to the glucose-FFA interaction.
Assuntos
Emulsões Gordurosas Intravenosas/farmacologia , Ácidos Graxos/fisiologia , Glucose/fisiologia , Puberdade/fisiologia , Criança , Feminino , Glucose/biossíntese , Técnica Clamp de Glucose , Humanos , Hiperinsulinismo/sangue , Insulina/sangue , Insulina/fisiologia , Fígado/metabolismo , MasculinoRESUMO
PIT1 abnormality is defined as a genetic abnormality in the PIT1 gene that encodes a pituitary specific transcription factor, Pit-1/GHF-1. PIT1 abnormality indicates combined deficiency of thyrotropin (TSH), growth hormone (GH) and prolactin (PRL), and has been reported in several cases. We studied the PIT1 gene in a patient with combined deficiency of TSH, GH and PRL. A novel mutation substituting a termination codon for Glutamate at 250th codon (E250X) was identified in the homozygous state in the patient. Both of the healthy parents harbored this mutation in the heterozygous state. This nonsense mutation results in complete loss of helix 3 of the POU homeodomain of Pit-1/GHF-1. As helix 3 of the homeodomain is involved directly in DNA binding, the mutant Pit-1/GHF-1 may lose the DNA binding activity of the POU homeodomain and lose its transcriptional activation. The E250X mutation is therefore considered to be the cause of the combined deficiency of TSH, GH and PRL in this patient.