[Euglycemic ketosis in an adolescent with type 1 diabetes on insulin and dapaglifozin: Case report]. / Cetosis normoglicémica en adolescente con diabetes tipo 1 recibiendo insulina y dapaglifozina: Reporte de un caso.

Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 inhibitor (SGLT2-I) induces glycosuria and reduces hyperglycemia in adults with type 2 diabetes. OBJECTIVE: To present an “euglycemic” diabetic ketosis in an adolescent with type 1 diabetes (T1D) receiving dapagliflozin, to alert about the risk of a drug not approved in children nor in T1D. CASE REPORT: A 17 years old adolescent with T1D during 9 years, was started on dapagliflozin 10 mg / day to reduce insulin dose and weight. During 11 months on treatment, capillaries ketones were undetectable and she exhibited a reduction in body mass index 23.9 to 21.1 kg/m2, basal insulin 40 to 17 U, glycated hemoglobin 8.3 to 7.5%, capillary glucose 175 to 161 mg/dl and glucose variability (standard deviation) 85 to 77. Suddenly nausea and vomits appeared. The patient was on an insulin pump and well calibrated continuous glucose monitoring, showing stable glucose levels under 200 mg/dl, and an insulin bolus was delivered. Vomiting without hyperglycemia persisted; three hours later, she was severely dehydrated and fainting, with ketones 4.6 nmol/l and glucose 224 mg/dl. She received IV saline fluids, ondansetron, carbohydrates and several insulin boluses. Hydration and general condition improved soon, however despite several insulin doses, ketosis continued for 24 hours. It is remarkable that the pump was working well and the cannula was not changed. After the ketosis was resolved, she continued using the same cannula with good metabolic control. CONCLUSION: Euglycemic ketosis is a life-threatening condition that must be suspected.

Cetosis normoglicémica en adolescente con diabetes tipo 1 recibiendo insulina y dapaglifozina: Reporte de un caso / Euglycemic ketosis in an adolescent with type 1 diabetes on insulin and dapaglifozin: Case report

Dapaglifozina, un inhibidor del cotransportador de sodio-glucosa 2 (I-SGLT2) induce glucosuria y reduce la glicemia en adultos con diabetes tipo 2. Objetivo: Presentar una cetosis diabética “normoglicémica” en una adolescente con diabetes tipo 1 (DM1) que recibía dapaglifozina y alertar sobre el riesgo del uso I-SGLT2 que parece promisorio, pero no está aprobado en niños ni en DM1. Caso clínico: Paciente de 17 años sin cetosis durante 9 años con DM1, inició dapaglifozina 10 mg/día para reducir la insulina y el peso. Durante 11 meses de tratamiento tuvo cetonas capilares indetectables, redujo el índice de masa corporal 23,9 a 21,1 kg/m², la insulina basal 40 a 17 U, la hemoglobina glicosilada 8,3 a 7,5%, la glicemia capilar 175 a 161 mg/dl y la variabilidad de la glucosa (desvío estándar 85 a 77). Inesperadamente aparecieron náuseas y vómitos. La paciente portaba bomba de insulina con monitorización continua de glucosa, bien calibrada (glucosas intersticiales concordantes con glicemias), que mostraba glucosa estable bajo 200 mg/dl. Recibió insulina pero los vómitos persistieron; en tres horas, aparecieron deshidratación y desmayos, con cetonas 4,6 nmol/l y glicemia 224 mg/dl. Recibió suero fisiológico, ondansetrón, carbohidratos y varias dosis de insulina con pronta recuperación del estado general e hidratación, sin embargo, la cetosis continuó durante 24 horas. Cabe destacar que la bomba estaba funcionando bien y no se cambió la cánula. Al superar la cetosis, continuó con la misma cánula con buen control metabólico. Conclusión: Es importante sospechar la cetosis diabética normoglicémica por ser de riesgo vital.

Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 inhibitor (SGLT2-I) induces glycosuria and reduces hyperglycemia in adults with type 2 diabetes. Objective: To present an “euglycemic” diabetic ketosis in an adolescent with type 1 diabetes (T1D) receiving dapagliflozin, to alert about the risk of a drug not approved in children nor in T1D. Case report: A 17 years old adolescent with T1D during 9 years, was started on dapagliflozin 10 mg / day to reduce insulin dose and weight. During 11 months on treatment, capillaries ketones were undetectable and she exhibited a reduction in body mass index 23.9 to 21.1 kg/m2, basal insulin 40 to 17 U, glycated hemoglobin 8.3 to 7.5%, capillary glucose 175 to 161 mg/dl and glucose variability (standard deviation) 85 to 77. Suddenly nausea and vomits appeared. The patient was on an insulin pump and well calibrated continuous glucose monitoring, showing stable glucose levels under 200 mg/dl, and an insulin bolus was delivered. Vomiting without hyperglycemia persisted; three hours later, she was severely dehydrated and fainting, with ketones 4.6 nmol/l and glucose 224 mg/dl. She received IV saline fluids, ondansetron, carbohydrates and several insulin boluses. Hydration and general condition improved soon, however despite several insulin doses, ketosis continued for 24 hours. It is remarkable that the pump was working well and the cannula was not changed. After the ketosis was resolved, she continued using the same cannula with good metabolic control. Conclusion: Euglycemic ketosis is a life-threatening condition that must be suspected.

[Metabolic control and school performance in children with type 1 diabetes]. / Control metabólico y rendimiento escolar en niños con diabetes tipo 1.

The impact of type 1 diabetes (T1D) on school performance is controversial. OBJECTIVE: To study the relationship between school performance and metabolic control in children with T1D (Ch-T1D), comparing their school grades to general population children (Ch-GP). PATIENTS AND METHOD: Clinical data for 66 Ch-T1D was reviewed, school grades were compared in Ch-T1D with Glycated Haemoglobin (HbA1c) HbA1c < 7.5% and ≥ 7.5%. School marks were also compared between Ch-T1D and Ch-GP from the same level, community and school type (public, private o chartered). Simple linear regression analysis and Mann Whitney test were used to compare groups. A p < 0.05 was considered significant. RESULTS: Ch-T1D were: 13.4 ± 2.9 years old, T1D duration: 5.3 ± 3.2 years, HbA1c was 8.6 ± 1.9% and capillary blood glucose was measured 3.2 ± 1.2 times per day. Grade averages showed no correlation with HbA1c, diabetes duration, hypothyroidism, mental health issues, neither with hypoglycemia or ketoacidosis records. However, primary education Ch-T1D showed lower grades than Ch-GP 5.6 ± 0.7 and 6.0 ± 0.2 (p = 0,0002). School grades correlated with the number of capillary blood glucose readings per day, Pearson correlation coefficient (r) 0.25, 0.41, 0.52 and 0.58 with general grade point average, math, language, and history average respectively (p < 0.05). School non-pass rate was 6.1% in Ch-T1D and 4.8% in Ch-GP (p = 0.65) and school dropout rate was 10.5% in Ch-T1D and 7.7% in Ch-GP (p = 0.47). CONCLUSION: Ch-T1D attending primary school showed lower school grades than Ch-GP, and patients who more frequently checked capillary blood glucose showed better school grades. T1D may have a deleterious impact on school performance.

Control metabólico y rendimiento escolar en niños con diabetes tipo 1 / Metabolic control and school performance in children with type 1 diabetes

El impacto de la diabetes tipo 1 (DM1) en el rendimiento escolar es controversial. Objetivo: Evaluar la relación entre rendimiento escolar y control metabólico en niños con DM1 (N-DM1) y comparar sus resultados con niños de la población general (N-PG). Pacientes y Método: Se revisaron datos clínicos de 66 N-DM1. Se compararon las calificaciones de N-DM1 según Hemoglobina Glicosilada (HbA1c) < 7,5% y ≥ 7,5% con N-PG del mismo nivel, comuna, tipo de colegio (municipal, particular subvencionado y particular pagado) y localidad. Para la comparación de los grupos se utilizó la regresión lineal simple y el test de suma de los rangos de Wilcoxon (Mann y Whitney) previa comprobación de incumplimiento de normalidad con el test de Shapiro-Wilk según el caso. Se consideró un valor de p < 0,05 como estadísticamente significativo con una confiabilidad del 95%. Resultados: La edad fue 13,4 ± 2,9 años, tiempo de evolución DM1 5,3 ± 3,2 años, HbA1c 8,6 ± 1,9% y controles de glicemia capilar 3,2 ± 1,2 veces por día. Las calificaciones no mostraron correlación con HbA1c, duración de DM1, hipotiroidismo, problemas de salud mental, antecedentes de hipoglicemia ni de cetoacidosis. N-DM1 de educación básica mostraron calificaciones inferiores a N-PG del mismo nivel 5,6 ± 0,7 vs 6,0 ± 0,2 (p = 0,0002). Las calificaciones se correlacionaron con el número de controles diarios de glicemia capilar, coeficiente de correlación de Pearson (r) de 0,25, 0,41, 0,52 y 0,58 con el promedio general, matemática, lenguaje e historia respectivamente (p < 0,05). Un 6,1% de N-DM1 y 4,8% de N-PG no fue promovido de curso (p = 0,65). La deserción escolar fue 10,5% en N-DM1 y 7,7% en N-PG (p = 0,47). Conclusión: N-DM1que cursaban educación básica tuvieron calificaciones inferiores a N-PG y los pacientes que controlaban su glicemia capilar con mayor frecuencia mostraron mejores calificaciones. La DM1 puede tener un impacto deletéreo en el rendimiento escolar.

The impact of type 1 diabetes (T1D) on school performance is controversial. Objective: To study the relationship between school performance and metabolic control in children with T1D (Ch-T1D), comparing their school grades to general population children (Ch-GP). Patients and Method: Clinical data for 66 Ch-T1D was reviewed, school grades were compared in Ch-T1D with Glycated Haemoglobin (HbA1c) HbA1c < 7.5% and ≥ 7.5%. School marks were also compared between Ch-T1D and Ch-GP from the same level, community and school type (public, private o chartered). Simple linear regression analysis and Mann Whitney test were used to compare groups. A p < 0.05 was considered significant. Results: Ch-T1D were: 13.4 ± 2.9 years old, T1D duration: 5.3 ± 3.2 years, HbA1c was 8.6 ± 1.9% and capillary blood glucose was measured 3.2 ± 1.2 times per day. Grade averages showed no correlation with HbA1c, diabetes duration, hypothyroidism, mental health issues, neither with hypoglycemia or ketoacidosis records. However, primary education Ch-T1D showed lower grades than Ch-GP 5.6 ± 0.7 and 6.0 ± 0.2 (p = 0,0002). School grades correlated with the number of capillary blood glucose readings per day, Pearson correlation coefficient (r) 0.25, 0.41, 0.52 and 0.58 with general grade point average, math, language, and history average respectively (p < 0.05). School non-pass rate was 6.1% in Ch-T1D and 4.8% in Ch-GP (p = 0.65) and school dropout rate was 10.5% in Ch-T1D and 7.7% in Ch-GP (p = 0.47). Conclusion: Ch-T1D attending primary school showed lower school grades than Ch-GP, and patients who more frequently checked capillary blood glucose showed better school grades. T1D may have a deleterious impact on school performance.

Growth hormone signaling in fibroblasts from newborn boys and prepubertal boys.

BACKGROUND/AIM: Responsiveness to GH in target cells is mediated by its receptor, which activates the Janus kinase-2 (JAK2) and STAT5 (signal transducers and activators of transcription 5) leading to the expression of IGF-1 and IGFALS. The aim of this study was to compare the GH signaling pathway in newborns and prepubertal boys. SUBJECTS AND METHODS: We determined the GHR protein content and the effect of stimulation with recombinant human GH (rhGH; 200ng/mL) on JAK2 and STAT5 phosphorylation in skin fibroblast cultures obtained from newborns and prepubertal boys. The transcript levels of IGFALS and IGF-I, were also studied and compared after 16h or 24h of stimulation with GH in both study groups. RESULTS: Newborn infants showed less GHR protein than the prepubertal boys. After rhGH stimulation, JAK2 and STAT5 phosphorylation was absent in skin fibroblasts from newborns, but was clearly detectable in prepubertal boys. After 16h of treatment with rhGH, IGFALS and IGF-I transcript levels increased in the prepubertal boys when compared to baseline. In newborns, however, we did not observe a response after 16 and 24h of rhGH stimulation. CONCLUSION: The significant attenuation of the GH signaling pathway observed in fibroblasts from newborn boys appears to be related to a reduction in GHR content and lack of phosphorylation of JAK2 and STAT5 in response to rhGH. This might impair STAT5 dimer formation, leading to a reduction in the transcript levels of IGFALS and IGF-I during the newborn period.

Effects of levothyroxine on growth hormone (gh) sensitivity in children with idiopathic short stature.

BACKGROUND: The possible relationship between the circulating concentrations of T4 and GH sensitivity has not been elucidated. OBJECTIVE: The aim of this study is to evaluate the effect of levothyroxine supplementation on GH sensitivity in prepubertal boys with idiopathic short stature (ISS). METHODS: We selected 28 prepubertal boys with ISS (mean age 8.2±0.5years) and free T4 (Ft4) concentrations between the 3rd and the 25th percentiles (Ft4: 0.8-1.5ng/dl). They were randomly divided into two groups: Group A received thyroid supplementation (1-3µg/kg/day) for 120days, and Group B received placebo for the same period. To evaluate GH sensitivity, an IGF-I generation test (GH: 33µg/kg/day sc for 3days) was performed in both groups: under basal conditions, and after 120days of levothyroxine supplementation (or placebo). RESULTS: After thyroid supplementation, Group A had higher Ft4 concentrations compared with Group B (2.14±0.06 vs 1.48±0.06ng/dl, p=0.01), their growth velocity was significantly higher (2.3±0.1 vs 1.5±0.2cm/4months), and they exhibited a greater increase in IGF-I after GH administration (Group A: 32.5±3.8% vs Group B 17.3±2.6%). CONCLUSION: Supplementation with levothyroxine for 120days promotes an increase in growth velocity, and a greater IGF-I response to short-term GH administration in prepubertal boys with ISS and low-normal thyroid hormone concentrations.

Effects of thyroid hormone on the GH signal transduction pathway.

BACKGROUND/AIM: The importance of thyroid hormone on growth and development in children is well recognized. In addition, linear growth is highly dependent on the response of peripheral tissues to growth hormone, a process known as GH sensitivity, but little is known about the possible effects of T4 on this process. METHODS: We determined the effect of stimulation with recombinant human GH (rhGH; 200 ng/mL) alone or in combination with two different concentrations of T4 (250 nM and 500 nM for 24 h) on JAK2 and STAT5 activation in skin fibroblast cultures obtained from prepubertal boys with normal height. RESULTS: JAK2 and STAT5 were activated under co-incubation with T4 (at both concentrations) and rhGH in the non-nuclear fraction of the fibroblasts. In addition, after 24h of co-incubation with rhGH and T4 (500 nM), we observed an increase in phospho-STAT5 in the nuclear fraction, when compared to GH and T4 stimulation alone. This effect was not observed when the fibroblasts were co-incubated with GH and the lower concentration of T4 (250 nM). CONCLUSION: Combined stimulation with GH and T4 at a concentration of 500 nM increases synergistically nuclear phospho-STAT5 in skin fibroblasts, which may amplify tissue sensitivity to GH. These findings may help to explain the effect of T4 administration on growth velocity in some children with idiopathic short stature.

Phosphotyrosine phosphatases in GH-stimulated skin fibroblasts from children with idiopathic short stature.

AIM: Some cases of idiopathic short stature (ISS) may be caused by defects in the modulation of the negative feedback regulation of the growth hormone receptor (GHR)/ Janus kinase (JAK)2/signal transducers and activators of transcription (STAT)5 signaling pathway. The cytosolic tyrosine phosphatases, protein tyrosine phosphatase 1B (PTP1B) and Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase-1 (SHP-1), the later which translocates to the nucleus after activation, interact with JAK2 in a GH-dependent manner. The possible contribution of PTP1B and SHP-1 to GH signaling in fibroblasts from ISS patients has not been studied. METHODS: We determined the basal protein content of PTP1B and SHP-1 in the presence of recombinant human GH (rhGH) for 24 h in skin fibroblast cultures, obtained from patients with ISS, and were compared with a normal height control children group. JAK2 activation was determined in both groups. RESULTS: JAK2 activation was delayed in fibroblasts from ISS patients compared to controls. Under basal conditions, the protein content of SHP-1 was lower in ISS, and after incubation with rhGH, it decreased in the non-nuclear and nuclear fraction of controls, but not in ISS patients. The protein content of PTP1B, however, increased in a similar fashion in fibroblasts from both ISS and control children. CONCLUSION: The delayed activation of JAK2 and the lack of response of SHP-1 after incubation with GH in fibroblasts from ISS patients, suggests that the growth retardation observed in some of these children may be mediated in part by this phosphotyrosine phosphatase.

Rebrote virológico en el tratamiento de hepatitis B con entecavir: ¿resistencia? / Virological breakthrough in treating hepatitis B with entecavir: It means resistance?

Paciente varón de 45 años natural de Lima, casado con antecedentes de , múltiples parejas sexuales y operado de fimosis, que debuta con eritema nodoso y diagnosticado de hepatitis B crónica en Agosto del 2008, en controles por consultorio se realiza diagnóstico de cirrosis hepática child A y hepatocarcinoma. Inicia tratamiento para la hepatitis B con Entecavir 0,5mg y luego se realiza hepatectomía del segmento V, En Febrero 2009 en controles de imágenes se evidencia recidiva de hepatocarcinoma en el segmento VI (lesión de 14mm) con AFP de 68 ng/dl, se realiza etanolización, con evolución final favorable. Durante el seguimiento no se observa evidencia de recidiva de HCC, continua con Entecavir 0,5 mg /d y en abril 2010, luego de 72 semanas de tratamiento con adecuada adherencia al tratamiento presenta rebrote virológico (carga viral positiva de 646 UI/dl), y se decide agregar a la terapia Tenofovir. Actualmente paciente con buena evolución con última carga viral de Abril del 2012 negativa recibiendo terapia doble para VHB. Reportamos el caso por ser uno de los primeros en nuestro país de resistencia probable a Entecavir y donde se pone de manifiesto la necesidad de examenes complementarios que confirmen dicha sospecha.

A 45 year- old - married man, with several sexual partners, initiated symptoms with nodosum erythema and in August 2008, is diagnosed of chronic hepatitis due to hepatitis B virus (HBV). Later he was diagnosed of Child A cirrhosis and hepatocarcinoma. He began HBV treatment with Entecavir 0,5 mg; then he underwent a V segment hepatectomy. In February 2009 he presented a relapse with a tumor of 14 mm on VI segment with AFP values of 68 ng/dl, so he underwent an ethanolization with good evolution. During the follow up, he has not presented evidence of relapse of hepatocarcinoma and continued with Entecavir 0,5 mg/d. In April 2010, after 72 weeks of therapy with good compliance, the patient presented a virological breakthrough (viral load 646 UI/dl) and Tenofovir was added to his therapy. Nowadays the patient is receiving double therapy for HBV and his last viral load, April 2012, was negative. This could be the first case in our country of a probable resistance to Entecavir; complementary tests are needed in order to rule out this suspicion.

Expression of SOCS1, SOCS2, and SOCS3 in growth hormone-stimulated skin fibroblasts from children with idiopathic short stature.

BACKGROUND/AIM: Possible etiologies of idiopathic short stature (ISS) include a range of conditions, some of which may be caused by defects in the modulation of the growth hormone (GH)-signaling pathway. The Janus kinase/signal transducer and activator of transcription pathway is regulated by several mechanisms, including negative feedback regulation by the suppressors of cytokine signaling (SOCS). However, the specific induction of SOCS transcript levels in fibroblasts from ISS patients has not been studied. METHODS: We determined the transcript levels of the SOCS1-3 genes under basal conditions, and in the presence or absence of stimulation with rhGH for 24 h in skin fibroblast cultures obtained from patients with ISS and children with normal height. RESULTS: Under basal conditions, ISS patients express higher SOCS2-3 transcript levels than control children. After incubation with recombinant human GH (rhGH), the transcript levels of SOCS2 increased significantly in ISS patients compared to controls (0.79 +/- 0.06 vs. 0.55 +/- 0.07; p = 0.03), a pattern which did not achieve statistical significance for SOCS3 transcript levels (0.55 +/- 0.08 vs. 0.40 +/- 0.07). CONCLUSION: The higher baseline transcript levels of the SOCS genes, and the increase observed for SOCS2 after rhGH treatment in ISS patients, suggest that growth retardation in some of these children may be mediated, at least in part, by intracellular overexpression of the SOCS genes.

Prevalence of components of the metabolic syndrome according to birthweight among overweight and obese children and adolescents.

BACKGROUND/OBJECTIVES: Extremes of birthweight (BW) have been associated with increased rates of metabolic risks. The objective was to study the prevalence of metabolic risks markers among obese and overweight (OW) subjects according to BW. SUBJECTS/METHODS: A cross-sectional study was performed in a cohort of 1002 patients (2-18 years, 40.6% male) evaluated for OW or obese subjects in two private clinics. Anthropometrics, fasting lipids, glycemia, and insulin were obtained. RESULTS: Of the subjects, 76.1% were born appropriate for gestational age (AGA), 10.9% small for gestational age (SGA), and 13% large for gestational age (LGA). Children born LGA presented a more severe degree of obesity compared with those born AGA and SGA (p<0.0001). No differences in glycemia, insulin, and lipid levels were detected among the groups. Abnormal glucose was found in 37 subjects: one with type 2 diabetes mellitus (from the previously glucose-intolerant subjects), 10 with glucose intolerance, and 27 with impaired fasting glucose. According to Boney criteria, 6.6% of the patients (6-18 years old) exhibited metabolic syndrome (MS) (69.4% AGA, 12.9% SGA, and 17.7% LGA). CONCLUSIONS: Being born LGA represents a higher risk of severe obesity. At this age, the most frequent component of MS was an abnormal lipid profile with low high-density lipoprotein and high triglycerides. Finally, the most frequent finding associated with abnormalities of glucose tolerance was a family history of diabetes. Thus, BW, lipid profile, and family history are mandatory when these patients are evaluated.

[Virological breakthrough in treating hepatitis B with entecavir: it means resistance?]. / Rebrote virológico en el tratamiento de hepatitis B con entecavir ¿resistencia?

A 45 year-old married man, with several sexual partners, initiated symptoms with nodosum erythema and in August 2008, is diagnosed of chronic hepatitis due to hepatitis B virus (HBV). Later he was diagnosed of Child A cirrhosis and hepatocarcinoma. He began HBV treatment with Entecavir 0.5 mg; then he underwent a V segment hepatectomy. In February 2009 he presented a relapse with a tumor of 14 mm on VI segment with AFP values of 68 ng/dl, so he underwent an ethanolization with good evolution. During the follow up, he has not presented evidence of relapse of hepatocarcinoma and continued with Entecavir 0.5 mg/d. In April 2010, after 72 weeks of therapy with good compliance, the patient presented a virological breakthrough (viral load 646 UI/dl) and Tenofovir was added to his therapy. Nowadays the patient is receiving double therapy for HBV and his last viral load, April 2012, was negative. This could be the first case in our country of a probable resistance to Entecavir; complementary tests are needed in order to rule out this suspicion.

[Prevalence of metabolic syndrome in children and adolescents who consult with obesity]. / Prevalencia de síndrome metabólico en niños y adolescentes que consultan por obesidad.

BACKGROUND: The higher prevalence of childhood obesity has led to search for metabolic syndrome (MS) in this age group. AIM: To study the prevalence of MS in obese children and adolescents. MATERIAL AND METHODS: Cross sectional study of 255 obese children and adolescents aged 11.3 ± 2.4 years, 45% males, 60% pubertal, with a body mass index (BMI) z score of 2.7 ± 0.6, who were evaluated for obesity. MS was defined as the presence of at least three of the following criteria, according to Ferranti: fasting glucose (FG) ≥ 100 mg/dl, triglycerides (TG) ≥ 100 mg/dl, HDL < 50 mg/dl, waist circumference (WC) > percentile (p) 75 and blood pressure (BP) > p90. Patients were also classified using Cook criteria: FG ≥ 100 mg/dl, TG ≥ 110 mg/dl, HDL < 40 mg/dl, WC > p 90, BP > p 90. RESULTS: MS was observed in 45 and 22.7% of patients, according to Ferranti and Cook definitions, respectively. WC was the most frequent criteria and glucose was the most uncommon. Males had higher body mass index, WC and TG levels than females. According to Ferranti and Cook definitions, MS prevalence was 53.5 and 28% in males and 37.6 and l8.4% in females (p < 0.05). Fifty and 26.1% of pubertal patients exhibited MS vs 36.9 and 17.5% in pre-pubertal subjects (p < 0.05) using Ferranti and Cook criteria, respectively. The frequency of MS increased along with a higher BMI. CONCLUSIONS: MS is a prevalent condition in obese children and adolescents, especially in males and pubertal children. It is necessary to have a better and universal definition for MS in pediatrics including all ages, in order to be focused in obesity prevention and treatment.

Prevalencia de síndrome metabólico en niños y adolescentes que consultan por obesidad / Prevalence of metabolic syndrome in children and adolescents who consult with obesity

Background: The higher prevalence of chüdhood obesity has led to search for metabolic syndrome (MS) in this age group. Aim: To study the prevalence of MS in obese children and adolescents. Material ana Methods: Cross sectional study of 255 obese children and adolescents aged 11.3 ± 2.4 years, 45 percent males, 60 percent pubertal, with a body mass Índex (BMI) z score of 2.7 ± 0.6, who were evaluated for obesity. MS was defined as the presence of at least three of the following criteria, according to Ferranti: fasting glucose (FG) ≥ 100 mg/dl, triglycerides (TG) ≥ 100 mg/dl, HDL < 50 mg/dl, waist circumference (WC) > percentile (p) 75 and blood pressure (BP) > p90. Patients were also classified using Cook criteria: FG ≥100 mg/dl, TG ≥ 110 mg/dl, HDL < 40 mg/dl, WC > p 90, BP > p 90. Results: MS was observed in 45 and 22.7 percent of patients, according to Ferranti and Cook definitions, respectively. WC was the most frequent criteria and glucose was the most uncommon. Males had higher body mass Índex, WC and TG levéis than femóles. According to Ferranti and Cook áefinitions, MS prevalence was 53.5 and 28 percent in males and 37.6 andl8.4 percent in fernales (p < 0.05). Fifty and 26.1 percent of pubertal patients exhibited MS vs 36.9 and 17.5 percent in pre-pubertal subjects (p < 0.05) using Ferranti and Cook criteria, respectively. The frequency of MS increased along with a higher BMI. Conclusions: MS is a prevalent condition in obese children and adolescents, especially in males and pubertal children. It is necessary to have a better and universal definition for MS in pediatrics including all ages, in order to be focused in obesity prevention and treatment.

Menarche delay and menstrual irregularities persist in adolescents with type 1 diabetes.

BACKGROUND: Menarche delay has been reported in adolescent females with type 1 diabetes (T1DM), perhaps due to poor glycemic control. We sought to compare age at menarche between adolescent females with T1DM and national data, and to identify factors associated with delayed menarche and menstrual irregularity in T1DM. METHODS: This was a cross-sectional study and females ages 12- 24 years (n = 228) with at least one menstrual period were recruited during their outpatient diabetes clinic appointment. The National Health and Nutrition Examination Survey (NHANES) 2001-2006 data (n = 3690) for females 12-24 years were used as a control group. RESULTS: Age at menarche was later in adolescent females with T1DM diagnosed prior to menarche (12.81 +/- 0.09 years) (mean+/- SE) (n = 185) than for adolescent females diagnosed after menarche (12.17 0.19 years, p = 0.0015) (n = 43). Average age of menarche in NHANES was 12.27 +/- 0.038 years, which was significantly earlier than adolescent females with T1DM prior to menarche (p < 0.0001) and similar to adolescent females diagnosed after menarche (p = 0.77). Older age at menarche was negatively correlated with BMI z-score (r = -0.23 p = 0.0029) but not hemoglobin A1c (A1c) at menarche (r = 0.01, p = 0.91). Among 181 adolescent females who were at least 2 years post menarche, 63 (35%) reported usually or always irregular cycles. CONCLUSION: Adolescent females with T1DM had a later onset of menarche than both adolescent females who developed T1DM after menarche and NHANES data. Menarche age was negatively associated with BMI z-score, but not A1c. Despite improved treatment in recent decades, menarche delay and high prevalence of menstrual irregularity is still observed among adolescent females with T1DM.

Ghrelin plasma levels in patients with idiopathic short stature.

BACKGROUND: Novel molecular insights have suggested that ghrelin may be involved in the pathogenesis of some forms of short stature. Recently, growth hormone secretagogue receptor (GHSR) mutations that segregate with short stature have been reported. AIM: To study plasma ghrelin levels in prepubertal patients with idiopathic short stature (ISS). METHODS: Fasting total plasma ghrelin levels (radioimmunoassay) in 41 prepubertal patients with ISS (18 females, age 7.9 ± 0.5 years) compared with 42 age- and sex-matched controls (27 females, age 8.0 ± 0.3 years) with normal height. In a subset of 28 patients, the ghrelin receptor was sequenced. RESULTS: ISS patients exhibited a higher level of ghrelin (1,458 ± 137 vs. 935 ± 55 pg/ml, p < 0.01) and similar IGF-I levels (-0.66 ± 1.29 vs. -0.32 ± 0.78 SDS) compared to controls. Ten patients with ISS had ghrelin levels greater than +2 SDS compared to controls. These patients did not differ in height, BMI or IGF-I SDS compared to ISS patients with ghrelin levels within the normal range. Molecular analysis of GHSR did not show any mutations, but showed some polymorphisms. CONCLUSION: These results suggest that in ISS patients, short stature does not appear to be frequently caused by abnormalities in ghrelin signaling.

[Diabetes as a risk factor for infections in cirrhotic patients]. / Diabetes como Factor de Riesgo para Infecciones en Pacientes Cirróticos.

AIMS AND OBJECTIVES: Infections are a common cause of morbidity and mortality in cirrhotic patients. Diabetes Mellitus (DM) is a predisposing factor for infections, and coexistence of DM and cirrhosis has increased in the last years, particularly in cirrhosis caused by hepatitis C virus. The aim of this study was to determine if there is an association between DM and infections in patients with cirrhosis. METHODS: Retrospective, cross sectional, analytical, multicenter study. Patients included were distributed in two groups: those with DM (glucose > 126 mg/dl) and those without DM. Frequency and type of infections were compared between both groups. Data was analyzed using Student's t test, Chi square, and Odds ratio analysis. RESULTS: 178 patients were included, 60.1% were male. Range age was between 25 and 88 years, and 25.8% reported DM. There were no demographic differences between groups. The frequency of infections in the DM group was 84.8% as compared to 48.5% in the controls (p=0.001; OR = 5.9). The most common infections were Urinary Tract Infection (UTI), Pneumonia, and Cellulites. We found a higher frequency of Pneumonia in the DM group, not so for UTI and Cellulites population. CONCLUSIONS: The occurrence of DM is a risk factor for infections in patients with hepatic cirrhosis, particularly increased is the risk for acquiring Pneumonia. KEYWORDS: Cirrhosis, Diabetes mellitus, Infections.

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.

Diabetes como factor de riesgo para infecciones en pacientes cirróticos / Diabetes as a risk factor for infections in cirrhotic patients

INTRODUCCIÓN: Las infecciones son causa común de morbi-mortalidad en pacientes cirróticos. La Diabetes Mellitus (DM) es un reconocido factor predisponente a infecciones y cuya coexistencia como causa o consecuencia se ha visto incrementada en la poblacióncirrótica, de manera particular en población cirrótica de etiología viral de tipo C y cuya prevalencia ha sido reportada hasta en más del 50 por ciento de pacientes en algunas series. Partimos de la hipótesis que la DM constituye un factor de riesgo para infecciones en los pacientes con Cirrosis Hepática. Nos planteamos el siguiente objetivo general: Determinar si existe asociación entre DM e infecciones en pacientes con cirrosis hepática. MATERIAL Y MÉTODOS: Estudio transversal, analítico, multicéntrico. Se dividió en 2 grupos, aquellos con DM (glicemia > 126 mg/dl) y sin DM. Se realizó una comparación de frecuencia y el tipo de infecciones en cada grupo. El análisis se realizó mediante las pruebas t Student, Chi Cuadrado y Odds Ratio como medida de asociación. RESULTADOS: Se incluyeron 178 pacientes (60,1 por ciento varones) entre 25 y 88 años. El 25,8 por cientotuvieron DM. No hubo diferencias demográficas entre los grupos DM y NDM. La frecuencia de infecciones en DM fue de 84,8 por ciento comparada con 48,5 por ciento en los no DM (p = 0,001 y OR = 5,90). Las infecciones más comunes fueron infecciones urinarias (ITU), neumonías y celulitis. Encontramos una mayor frecuencia de neumonías en el grupo DM, no así de ITU ni celulitis. CONCLUSIÓN: Existe una mayor frecuencia de infecciones en los pacientes cirróticos con DM. La frecuencia de Neumonías es mayor entre cirróticos infectados con DM, no así la de ITU o de celulitis.

AIMS AND OBJECTIVES: Infections are a common cause of morbidity and mortality in cirrhotic patients. Diabetes Mellitus (DM) is a predisposing factor for infections, and coexistence of DM and cirrhosis has increased in the last years, particularly in cirrhosis caused by hepatitis C virus. The aim of this study was to determine if there is an association between DM and infections in patients with cirrhosis. METHODS: Retrospective, cross sectional, analytical, multicenter study. Patients included were distributed in two groups: those with DM (glucose > 126 mg/dl) and those without DM. Frequency and type of infections were compared between both groups. Data was analyzed using Student´s t test, Chi square, and Odds ratio analysis. RESULTS: 178 patients were included, 60.1 percent were male. Range age was between 25 and 88 years, and 25.8 percent reported DM. There were no demographic differences betweengroups. The frequency of infections in the DM group was 84.8 percent as compared to 48.5 percent in the controls (p=0.001; OR = 5.9). The most common infections were Urinary Tract Infection (UTI), Pneumonia, and Cellulites. We found a higher frequency of Pneumonia in the DM group, not so for UTI and Cellulites population. CONCLUSIONS: The occurrence of DM is a risk factor for infections in patients with hepatic cirrhosis, particularly increased is the risk for acquiring Pneumonia.