Growth hormone directly favors hepatic ketogenesis in persons with prediabetes or type 2 diabetes mellitus treated with empagliflozin.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors increase glucagon secretion by pancreatic alpha cells and the susceptibility to ketoacidosis. On the other hand, growth hormone (GH) stimulates peripheral lipolysis and provides free fatty acids (FFA) for ketogenesis; however, it remains unresolved whether GH directly impacts hepatic ketogenesis. We aimed to investigate the role of physiologic GH levels in promoting ketogenesis in prediabetic or type 2 diabetic patients under empagliflozin treatment. METHODS: Sixteen patients (11 women, 5 men) with prediabetes or type 2 diabetes mellitus, aged 55.6 ± 4.7 years and with a mean BMI of 30.7 ± 4.8 kg/m2 and HbA1c 7.1 ± 1.6% (means ± SD), participated in this study. All of them were submitted to three mixed-meal tests: they received placebo at -60 min (test 1), and empagliflozin 25 mg (test 2, 21st day) and empagliflozin 25 mg plus pegvisomant 30 mg were administered subcutaneously 36 h before (test 3, 28th day). After test 1, all patients were instructed to take empagliflozin 25 mg daily. RESULTS: The empagliflozin treatment decreased the plasma concentrations of glucose by 14% (P < 0.01), FFA by 23% (P < 0.01), and the insulin/glucagon ratio by 26% (P < 0.01), and it increased ß-hydroxybutyrate by 44% (P < 0.05). The GH receptor block by pegvisomant restored the plasma ß-hydroxybutyrate to baseline levels. CONCLUSIONS: We conclude that GH has a direct effect on promoting the ketogenesis environment in patients treated with empagliflozin.

Silver serum levels in burned patients treated with silver sulfadiazine and its toxicity on inflammatory cells.

BACKGROUND: Silver sulfadiazine (SSD) has been widely used in burned patients for the prevention of local infections. To be biologically active and exert antimicrobial properties, silver needs to be present in the form of silver ions (Ag1+) that bind to negatively charged proteins, namely, the RNA and DNA in microorganisms. However, previous published studies conducted with SSD in the 1990s reported a high level of silver absorption through damaged skin and noted the potential cytotoxicity of Ag1+ to human cells. SSD toxicity, however, had been described in cell cultures using arbitrary silver concentrations. In the present study, we determined the serum silver levels in burned patients treated with SSD and, taking into account the molar Ag1+ concentrations found in these patients, we evaluated the Ag1+ toxicity effects on inflammatory cells (ROS and cytokine production) in vitro. METHODS: Twenty patients with an average burned body surface area of 27.68% were included in this study. RESULTS: Patients' Ag1+ serum levels reached up to 558 times those of the unexposed controls. Ag1+ was then added to inflammatory cells in vitro at levels up to 2000 times the level of the control, and there was no effect on the viability of the cells nor on the rate of apoptosis. We observed a decrease in reactive oxygen species production by mononuclear (MN) and polymorphonuclear (PMN) cells, as well as a substantial decrease in cytokines IL-1ß, IL-6, IL-8, IL-10, and TNF-α production by leukocytes (MN and PNM). CONCLUSION: These findings suggest that Ag1+ may contribute to negative outcomes after burns, decreasing the primary defense mechanism (respiratory burst) and altering cytokine production.

Prevalence of metabolic syndrome and associated risk factors in Brazilian schoolchildren.

OBJECTIVE: To determine the prevalence of metabolic syndrome (MetS) in schoolchildren from 6 to 16 years old, while considering their socio-economic status and other potential risk factors. DESIGN: A cross-sectional study was conducted between April and November of 2005 in a semi-rural city with a total population of 13,000 inhabitants. SETTING: The study was conducted in Maracai city, located in the Brazilian state of Sao Paulo. SUBJECTS: Schoolchildren (n 2170) of both genders, corresponding to approximately 82% of all Maracai schoolchildren, were evaluated for components of MetS, as defined by the National Cholesterol Education Program; reference values for children and adolescents were adjusted for age and sex. RESULTS: Overall, MetS prevalence was 3.6% (95% CI 2.9, 4.5) and did not differ statistically between genders, skin colour, between children and adolescents. However, when we analysed groups of subjects by weight, MetS prevalence progressively increased from 0.3% (95% CI 0.1, 0.8) in normal-weight subjects to 10.7% (95% CI 7.4, 14.8) and 34.5% (95% CI 25.9, 43.9) in overweight and obese subjects, respectively (both P < 0.001 compared to normal-weight controls). When socio-economic classes were considered, 4.7% high-income students (95% CI 3.5, 6.2) had MetS, which was significantly greater than low-income students (2.7%; 95% CI 1.9, 3.9; P = 0.023). CONCLUSIONS: MetS prevalence was high in overweight and obese schoolchildren and these risk factors were present during childhood and adolescence. Changes in lifestyle and alimentary safety should be encouraged to avoid future cardiovascular morbidity and type 2 diabetes mellitus.

Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects.

OBJECTIVE: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENT(S): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. RESULT(S): Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. CONCLUSION(S): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.

Adrenocorticotropic hormone but not high-density lipoprotein cholesterol or salivary cortisol was a predictor of adrenal insufficiency in patients with septic shock.

Relative adrenal insufficiency in sepsis has been extensively debated on; however, accurate diagnosis and therapeutic intervention remain controversial. The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and lipoproteins as predictors of adrenal insufficiency in patients within 24 h of septic shock diagnosis. This prospective study evaluated all hospitalized patients older than 18 years who developed septic shock and were using vasoactive drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline and 60 min (T60) after 250 µg tetracosactide intravenous injection. Patients were divided into two groups: responders (Δ [T60 minus baseline] total cortisol >9 µg/dL) and nonresponders (Δ total cortisol ≤ 9 µg/dL or baseline total cortisol <10 µg/dL). The latter group was considered to have adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and 34 subjects with septic shock were included in the analysis. Adrenal insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein cholesterol, triglycerides, and salivary cortisol did not differ between groups. Estimated plasma-free cortisol was not better than total plasma cortisol in estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL. Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could predict adrenal response to tetracosactide.

Impaired antioxidant action of high density lipoprotein in patients with type 1 diabetes with normoalbuminuria and microalbuminuria.

AIMS: Patients with type 1 diabetes, in the absence of chronic complications, have serum concentrations of high density lipoprotein cholesterol (HDL-C) similar to the general population. However, their HDL particles may be dysfunctional. We aimed to evaluate the antioxidant effect of HDL2 and HDL3 obtained from Caucasian males with type 1 diabetes with normoalbuminuria and microalbuminuria. METHODS: Twenty Caucasian men with type 1 diabetes (10 with normoalbuminuria and 10 with microalbuminuria) and 10 healthy Caucasian men participated in the study. Lipoproteins were obtained by density gradient ultracentrifugation. The antioxidant effect of HDL was assessed by measuring lipid hydroperoxide (LOOH) concentration after 3h of pooled LDL oxidation catalyzed by 5µM CuSO4 in the absence or presence of HDL2 or HDL3. RESULTS: The control, normoalbuminuria, and microalbuminuria groups had similar HDL-C concentration and estimated glomerular filtration rate. Glycemic control was similar between diabetes groups (HbA1c 8.1±0.9% and 8.3±0.7%, P=0.70), but estimated glucose disposal rate was lower in patients with microalbuminuria (8.0±0.6 and 4.5±1.1mg/kg/min, P<0.01). The relative antioxidant effect of HDL2 from control, normoalbuminuria, and microalbuminuria groups were 92.8±2.4%, 85.4±1.7%, and 74.2±4.6%, respectively (P<0.01), and the HDL3 effect were 95.0±2.2%, 86.4±4.4%, and 75.3±4.2%, respectively (P<0.01). CONCLUSION: Both HDL2 and HDL3 inhibited LOOH formation in copper-catalyzed oxidation of LDL in vitro. Overall, this antioxidant effect was lower in Caucasian men with type 1 diabetes, and was further compounded in those with microalbuminuria.

Avaliação dos intervalos de referência de lípides e lipoproteínas para crianças e adolescentes: associação das dislipidemias e sobrepeso em escolares de 4 a 19 anos de idade de Maracaí (São Paulo) / Evaluation of lipids and lipoproteins range values for children and adolescents: associations of dyslipidemia to overweight in schoolchildren from 4 to 19 years old from Maracaí (State of São Paulo)

OBJETIVO: Avaliar os intervalos de referência de lípides e lipoproteínas estabelecidos para crianças e adolescentes de Maracaí, São Paulo, através das associações das dislipidemias com sobrepeso em escolares de quatro a 19 anos de idade daquela cidade. MÉTODOS: Foram determinados perfis lipídicos e índices antropométricos de 2.481 estudantes de ambos sexos estratificados em duas faixas etárias de quatro a nove anos (n = 1.121) e dez a 19 anos (n = 1.360). Os pontos de corte para categorizar as dislipidemias foram estabelecidos em estudos prévios sobre os intervalos de referência de lípides e lipoproteínas para crianças e adolescentes de Maracaí. RESULTADOS: Na faixa etária de quatro a nove anos, as associações de triglicérides > 130mg/dl (ambos os sexos) e colesterol da lipoproteína de baixa densidade (LDL-C) > 101,1mg/dl (sexo masculino), com sobrepeso, foram estatisticamente significativas. Entre os alunos de 10 a 19 anos, as associações de triglicérides > 131mg/dl (ambos os sexos), de colesterol total > 161,3mg/dl (sexo masculino) e LDL-C > 93mg/dl (sexo masculino), com sobrepeso, foram estatisticamente significativas. Os valores de corte estabelecidos pelo percentil 5 de colesterol da lipoproteína de alta densidade (HDL-C), para ambos os sexos e grupos etários, não apresentaram associações estatisticamente significativas com sobrepeso. CONCLUSÃO: Os resultados apresentados fornecem subsídios para estudos sobre os intervalos de referência de lípides e lipoproteínas, para crianças e adolescentes, e permitem ampliar discussões sobre os valores dos pontos de corte adequados que possam definir dislipidemias na população infanto-juvenil brasileira.

OBJECTIVE: To evaluate the lipids and lipoproteins range values established for children and adolescents from Maracaí, State of São Paulo, through the associations of dyslipidemia and overweight in students from four to 19 years old, from that city. METHODS: The lipid profiles and anthropometric indexes were determined for 2,481 students of both sexes, separated into two age ranges from four to nine (n = 1,121) and ten to 19 (n = 1,360). The cut-points to rank the dyslipidemia have been set up in previous works on range values for lipids and lipoproteins for children and adolescents from Maracaí, State of São Paulo. RESULTS: In the four to nine years old, the associations of triglycerides > 130mg/dl (for both sexes) and of LDL-cholesterol > 101.1 mg/dl (male) to overweight were statistically significant. Among the students from ten to 19 years old, the associations of triglyceride > 131mg/dl (both sexes), of total cholesterol > 161.3mg/dl (male) and LDL-cholesterol > 93mg/dl (male) were statistically significant. The cut-points established by percentile 5 of HDL-cholesterol for both sexes and age group did not show significant associations to overweight. CONCLUSION: The achieved results supply evidence for studies on the range values for lipids and lipoproteins for children and adolescents, and allow for broadening the discussions on the values for reasonable cut-points that could define dyslipidemia within the Brazilian population of children and youngsters.

Perfil lipídico: intervalos de referência em escolares de 2 a 9 anos de idade da cidade de Maracaí (SP) / Lipid profile: normal range values in school children from two to nine years old from the city of Maracaí, SP, Brazil

INTRODUÇÃO: As recentes publicações disponíveis em nosso meio sobre dislipidemias na infância indicam progressäo de uma silenciosa epidemia, que pode agravar as taxas de morbidade e mortalidade por doenças cardiovasculares nos próximos anos. Na falta de padronizaçäo dos intervalos de referência para populaçäo brasileira, muitos autores utilizam valores procedentes de outros países, em particular os recomendados pelas III Diretrizes Brasileiras Sobre Dislipidemias (III DBSD, 2001), que foram transcritos do National Cholesterol Education Program-NCEP (EUA, 1992). OBJETIVO: Estabelecer intervalos de referência para triglicerídeos (TG), colesterol total (CT) e frações em escolares de 2 a 9 anos de idade da cidade de Maracaí, SP. MÉTODOS: delineamento transversal. Foram avaliados perfis lipídicos de 1.202 alunos de seis escolas (cinco públicas e uma privada), de 2 a 9 anos de idade, no período de 25 de março a 8 de outubro de 2002. Empregaram-se reações enzimáticas para determinações de TG e CT, kits Johnson & Johnson, metodologia de química seca e auto-analisador Vitros 750. Utilizaram-se reagentes magnéticos (sulfato de dextran e cloreto de magnésio, Johnson & Johnson) para precipitaçäo de LDL-c e VLDL-c e subseqüente determinaçäo enzimática de HDL-c. O LDL-c foi obtido através de cálculo de Friedewald para TG abaixo de 400mg/dl; valores superiores a este foram determinados com kits Merck CHOD-PAP e leitura fotométrica. RESULTADOS: As exclusöes totalizaram 266 casos e os analisados, 936. Os valores obtidos na amostra estudada diferem dos intervalos de referência recomendados pelas III DBSD. As maiores variações dos resultados de Maracaí, em relaçäo às III DBSD, foram do percentil 95 de TG: 130mg/dl (+ 30 por cento); percentil 75 de LDL-c: 101,1mg/dl (-8,1 por cento); percentil 5 de HDL-c: 34mg/dl (-15 por cento). DISCUSSÄO: os intervalos de referência transcritos de outros países desconsideram diferenças étnicas, socioeconômicas e hábitos alimentares da populaçäo brasileira. Desta forma, estudos epidemiológicos que os utilizam podem conter indesejáveis vieses de mensuraçäo. Na prática clínica, a utilizaçäo dos intervalos de referência de outras procedências, nessa faixa etária para TG, pode provocar investigações adicionais desnecessárias e danos irreparáveis ao desenvolvimento das crianças através de intervenções desastradas sob forma de dietas hipocalóricas ou, pior ainda, prescriçäo de medicamentos...