RESUMO
INTRODUCTION: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, metabolic associated fatty liver disease, and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to treat obesity, with known anti-inflammatory properties. How the GLP-1RA exenatide effects inflammation in adolescents with obesity is not fully investigated. METHODS: Forty-four patients were randomized to receive weekly subcutaneous injections with either 2 mg exenatide or placebo for 6 months. Plasma samples were collected at baseline and at the end of the study, and 92 inflammatory proteins were measured. RESULTS: Following treatment with exenatide, 15 out of the 92 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL-18Rα was significantly lowered following treatment. CONCLUSIONS: Weekly injections with 2 mg of exenatide lowers circulating IL-18Rα in adolescents with obesity, which may be a potential link between exenatide and its anti-inflammatory effect in vivo. This contributes to exenatide's pharmaceutical potential as a treatment for obesity beyond weight control and glucose tolerance, and should be further studied mechanistically.
Assuntos
Diabetes Mellitus Tipo 2 , Artes Marciais , Obesidade Infantil , Adolescente , Humanos , Exenatida/uso terapêutico , Hipoglicemiantes/uso terapêutico , Obesidade Infantil/complicações , Peptídeos/uso terapêutico , Peçonhas/uso terapêutico , Inflamação/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêuticoRESUMO
BACKGROUND: There are still controversies whether insulin resistance (IR) develops in preterm born children during early childhood. OBJECTIVE: To investigate the role of leptin, soluble leptin receptor (sOB-R), adiponectin, visfatin and insulin sensitivity in the pathogenesis of possible IR in preterm born children during early childhood. PATIENTS AND METODS: Twenty-nine preterm small for gestational age (SGA) born children (Group 1) and 25 preterm appropriate for gestational age (AGA) born children (Group 2), matched for gestational age and sex were included in the study. Mean chronological age at investigation was 3.3±0.7years and not different between the groups. Blood samples for fasting blood glucose, insulin, proinsulin, adiponectin, leptin, sOB-R and visfatin were obtained. RESULTS: Mean height and weight standard deviation scores (SDS) at investigation were significantly lower in Group 1 than in Group 2, but there was no significant difference in body mass index (BMI) SDS between the groups. Catch-up growth (CUG) was higher in Group 1 than in Group 2. There was no difference regarding homeostasis model assessment for IR (HOMA-IR), leptin, sOB-R, adiponectin, proinsulin and visfatin values between the groups. In the whole group, log visfatin showed a negative correlation with Δweight SDS. There was a positive correlation between HOMA-IR and BMI SDS. Adiponectin levels showed a positive correlation with log visfatin levels in all groups. CONCLUSION: Preterm born children whether AGA or SGA do not show IR in early childhood if BMI is normal. Significant differences between the preterm SGA and preterm AGA groups regarding the adipocytokine levels were not detected.
Assuntos
Recém-Nascido Prematuro/sangue , Resistência à Insulina , Adiponectina/sangue , Adiponectina/metabolismo , Glicemia , Índice de Massa Corporal , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Insulina/sangue , Leptina/sangue , Leptina/metabolismo , Masculino , Nicotinamida Fosforribosiltransferase/sangue , Nicotinamida Fosforribosiltransferase/metabolismo , Nascimento Prematuro , Proinsulina/sangue , Receptores para Leptina/sangue , Receptores para Leptina/metabolismoRESUMO
Increased intestinal permeability (IIP) precedes several autoimmune disorders. Although Hashimoto's thyroiditis (HT) is the most common autoimmune disorder, the role of IIP in its pathogenesis had received little attention. Zonulin plays a critical role in IIP by modulating intracellular tight junctions. Rise of serum zonulin levels were shown to indicate IIP in human subjects. In this case-control study, we examined the hypothesis that patients with HT have IIP. We studied 30 children and adolescents with HT, and 30 patients with congenital hypothyroidism (CH) matched for age, gender and body mass index (BMI). Serum zonulin levels, free thyroxine (fT4), thyroid stimulating hormone (TSH), anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were measured. Zonulin levels were significantly higher in patients with HT than patients with CH (59.1±22.9 ng/mL vs. 43.3±32.9 ng/mL, p=0.035). In patients with HT, zonulin levels were positively correlated with weight (r=0.406, p=0.03), BMI (r=0.486, p=0.006) and levothyroxine dose (r=0.463, p=0.02). In patients with CH, zonulin levels were positively correlated with age (r=0.475, p=0.008), weight (r=0.707, p<0.001), BMI (r=0.872, p<0.001) and levothyroxine dose (r=0.485, p=0.007). After adjusting for age, weight, TSH and fT4 levels, serum zonulin was only associated with levothyroxine dose in patients with HT (R2=0.36, p=0.05). In patients with CH, only weight was associated with zonulin levels (R2=0.62, p<0.001). In conclusion, higher zonulin levels in children and adolescents with HT suggested IIP in these patients. Additionally, the association between zonulin levels and levothyroxine dose might imply a relationship between serum zonulin and disease severity.
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Doença de Hashimoto/complicações , Enteropatias/etiologia , Mucosa Intestinal/metabolismo , Adolescente , Autoanticorpos/sangue , Estudos de Casos e Controles , Criança , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/epidemiologia , Hipotireoidismo Congênito/metabolismo , Hipotireoidismo Congênito/patologia , Feminino , Haptoglobinas , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/metabolismo , Doença de Hashimoto/patologia , Humanos , Enteropatias/epidemiologia , Enteropatias/metabolismo , Enteropatias/patologia , Mucosa Intestinal/patologia , Masculino , Permeabilidade , Projetos Piloto , Precursores de Proteínas/sangue , Hormônios Tireóideos/sangue , Tireotropina/sangue , Tiroxina/sangue , Turquia/epidemiologiaRESUMO
Odaman-Al I, Gezdirici A, Yildiz M, Ersoy G, Aydogan G, Salcioglu Z, Tahtakesen TN, Önal H, Küçükemre-Aydin B. A novel mutation in the SLC19A2 gene in a Turkish male with thiamine-responsive megaloblastic anemia syndrome. Turk J Pediatr 2019; 61: 257-260. Thiamine-responsive megaloblastic anemia (TRMA) is a very rare syndrome characterized by the triad of early onset megaloblastic anemia, sensorineural deafness and diabetes mellitus. Here we report, a 5-year-old boy who presented with transfusion dependent anemia and diabetes mellitus and was diagnosed with TRMA. Besides reporting a novel mutation of the causative gene SLC19A2, we wanted to emphasize this syndrome in the aspect of coexistence of insulin dependent diabetes, transfusion dependent anemia and thrombocytopenia.
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Anemia Megaloblástica/genética , DNA/genética , Diabetes Mellitus/genética , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana Transportadoras/genética , Mutação , Deficiência de Tiamina/congênito , Anemia Megaloblástica/metabolismo , Pré-Escolar , Análise Mutacional de DNA , Diabetes Mellitus/metabolismo , Perda Auditiva Neurossensorial/metabolismo , Humanos , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Deficiência de Tiamina/genética , Deficiência de Tiamina/metabolismo , TurquiaRESUMO
Odaman-Al I, Gezdirici A, Yildiz M, Ersoy G, Aydogan G, Salcioglu Z, Tahtakesen TN, Önal H, Küçükemre-Aydin B. A novel mutation in the SLC19A2 gene in a Turkish male with thiamine-responsive megaloblastic anemia syndrome. Turk J Pediatr 2019; 61: 257-260. Thiamine-responsive megaloblastic anemia (TRMA) is a very rare syndrome characterized by the triad of early onset megaloblastic anemia, sensorineural deafness and diabetes mellitus. Here we report, a 5-year-old boy who presented with transfusion dependent anemia and diabetes mellitus and was diagnosed with TRMA. Besides reporting a novel mutation of the causative gene SLC19A2, we wanted to emphasize this syndrome in the aspect of coexistence of insulin dependent diabetes, transfusion dependent anemia and thrombocytopenia.
Assuntos
Anemia Megaloblástica/genética , DNA/genética , Diabetes Mellitus/genética , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana Transportadoras/genética , Mutação , Deficiência de Tiamina/congênito , Anemia Megaloblástica/epidemiologia , Anemia Megaloblástica/metabolismo , Pré-Escolar , Análise Mutacional de DNA , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Feminino , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/metabolismo , Humanos , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Deficiência de Tiamina/epidemiologia , Deficiência de Tiamina/genética , Deficiência de Tiamina/metabolismo , Turquia/epidemiologiaRESUMO
The CYP17A1 gene encodes the enzyme P450c17, which mediates both 17α-hydroxylase and 17,20-lyase activities and is essential for production of cortisol and sex steroids. Loss-of-function mutations of this gene cause 17α-hydroxylase/17,20-lyase deficiency, characterized by hypertension, hypokalemia and sexual infantilism. A 6-year-old phenotypically female patient presented with hypertension and hyperpigmentation. Her blood test results showed low cortisol and high adrenocorticotropic hormone (ACTH), progesterone, deoxycorticosterone and gonadotropin levels and were consistent with the diagnosis of 17α-hydroxylase/17,20-lyase deficiency. Her karyotype was 46XY. Genetic studies of the patient revealed a novel homozygous point mutation, c.1307G>A, within the coding sequence of the CYP17A1 gene. 17α-hydroxylase/17,20-lyase deficiency should be considered in the differential diagnosis of hypertension in children and adolescents, and physical examination of these patients should be done very carefully.
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Hiperplasia Suprarrenal Congênita/diagnóstico , Esteroide 17-alfa-Hidroxilase , Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/genética , Hormônio Adrenocorticotrópico/sangue , Criança , Feminino , Homozigoto , Humanos , Cariotipagem , Mutação Puntual , Esteroide 17-alfa-Hidroxilase/metabolismoRESUMO
OBJECTIVE: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. METHODS: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. RESULTS: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. CONCLUSION: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan.
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Cariotipagem , Síndrome de Turner/epidemiologia , Síndrome de Turner/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Prevalência , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Turquia/epidemiologiaRESUMO
OBJECTIVE: Children with Turner syndrome (TS) have a specific growth pattern that is quite different from that of healthy children. Many countries have population-specific growth charts for TS. Considering national and ethnic differences, we undertook this multicenter collaborative study to construct growth charts and reference values for height, weight and body mass index (BMI) from 3 years of age to adulthood for spontaneous growth of Turkish girls with TS. METHODS: Cross-sectional height and weight data of 842 patients with TS, younger than 18 years of age and before starting any therapy, were evaluated. RESULTS: The data were processed to calculate the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile values for defined ages and to construct growth curves for height-for-age, weight-for-age and BMI-for-age of girls with TS. The growth pattern of TS girls in this series resembled the growth pattern of TS girls in other reports, but there were differences in height between our series and the others. CONCLUSION: This study provides disease-specific growth charts for Turkish girls with TS. These disease-specific national growth charts will serve to improve the evaluation of growth and its management with growth-promoting therapeutic agents in TS patients.
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Estatura/fisiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Gráficos de Crescimento , Síndrome de Turner/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Cariótipo , Turquia , Síndrome de Turner/genética , Adulto JovemRESUMO
BACKGROUND/AIM: The exon 3-deleted/full-length (d3/fl) growth hormone (GH) receptor (GHR) polymorphism has been associated with responsiveness to GH therapy in some diagnostic groups. However, there are still controversies on this issue. To evaluate the effect of the GHR exon 3 polymorphism on growth after 1 and 2 years of GH therapy in Turkish patients with GH deficiency (GHD) and Turner's syndrome (TS) and the distribution of GHR exon 3 isoforms. MATERIALS AND METHODS: 218 patients with GHD (125 males/93 females) and 43 patients with TS were included in the study. The control group included 477 healthy adults aged from 18 to 57 years (54 females/423 males). Anthropometric parameters and insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were evaluated annually. GHR isoforms were studied using simple multiplex PCR. Height and body mass index were expressed as standard deviation score (SDS). RESULTS: There were no differences among TS, GHD and healthy adults regarding the distribution of GHR exon 3 isoforms (fl/fl, fl/d3 and d3/d3). There was a significant increase in height SDS in both diagnostic groups on GH therapy; however, there were neither differences in height SDS and Δheight velocity between fl/fl, fl/d3 and d3/d3 groups nor a correlation between the distribution of GHR exon 3 isoforms and change in IGF-1 SDS and IGFBP-3 SDS levels on GH therapy in either of the diagnostic groups. There was also no gender difference in GHR isoforms in healthy adults. CONCLUSION: The results suggest that responsiveness to GH therapy does not depend on the exon 3 GHR genotypes in GHD and TS patients.
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Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Polimorfismo Genético , Receptores da Somatotropina/genética , Síndrome de Turner/tratamento farmacológico , Síndrome de Turner/genética , Adolescente , Estatura/efeitos dos fármacos , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Éxons , Feminino , Deleção de Genes , Frequência do Gene , Estudos de Associação Genética , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Masculino , Receptores da Somatotropina/metabolismo , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Turquia , Síndrome de Turner/sangueRESUMO
OBJECTIVE: The exon 3-deleted/full-length (d3/fl) growth hormone receptor (d3/fl-GHR) polymorphism has been associated with responsiveness to GH therapy in some children and also with adult height variation in the general population. We aimed to evaluate the distribution of d3/fl-GHR polymorphism in a Turkish population. METHODS: The study included 477 (54 females/423 males) healthy adults with a mean±SD age of 31.1±9.0 years (range: 18-57). Height and body mass index (BMI) were expressed as standard deviation score (SDS) according to national standards. All adults had normal height and BMI SDSs (between -2 and +2). GHR exon 3 isoforms were studied by simple multiplex polymerase chain reaction method. Insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) values were also measured and expressed as SDS. RESULTS: The distribution of the GHR exon 3 genotypes in the Turkish healthy adults was 35% (n=167) for fl/fl, 39% (n=186) for fl/d3, and 26% (n=124) for d3/d3. There was no difference between genders in GHR exon 3 genotypes. Frequencies of fl allele and d3 allele were 54.5% and 45.5%, respectively. There were no differences in height SDS and BMI SDS among the three d3/fl-GHR genotype groups. There was a significant difference in IGFBP-3 SDS between fl/fl and fl/d3 groups (p=0.022). CONCLUSIONS: This study presents the results of GHR polymorphism in a Turkish population as a reference for further studies. The distribution was similiar to European populations. There were no correlations between GHR isoforms and height SDS or other clinical/biochemical characteristics of the individuals except for higher IGFBP-3 levels in the fl/d3 group as compared to the fl/fl group. Whether this finding implies an abnormality, needs further investigation.