Betatrophin Levels were Increased in Pregnant Women with or without Gestational Diabetes Mellitus and Associated with Beta Cell Function / Níveis de betatrofina aumentados em grávidas com ou sem diabetes mellitus gestacional e associados à função das células beta

Abstract Purpose betatrophin has been reported to boost β cell expansion in insulin resistant states. Pregnancy is a well-recognized physiological state of insulin resistance. Betatrophin levels in pregnant women and their relationships with metabolic variables remain to be elucidated. Methods A total of 49 pregnant women and 31 age-matched unpregnant women with normal glucose regulation (UP-NGR) were included. Among these subjects, according to results from 75 g oral glucose tolerance test (OGTT), 22 women were diagnosed as having gestational diabetes mellitus ( GDM ). Results Our study found that pregnant women, regardless of their glucose regulation status, had remarkably higher triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β). However, GDM patients had much lower HOMA-β compared with those of pregnant women with normal glucose regulation (P-NGR). Participants of the P-NGR group had almost 4 times higher levels of betatrophin than those of the UP-NGR group. Although betatrophin levels were lower in the GDM group than those of the P-NGR group, the difference did not reach statistical significance. Spearman correlation analysis showed that betatrophin levels were positively and significantly associated with total cholesterol, triglycerides, highdensity lipoprotein cholesterol (HDL-c), FINS and HOMA-β. However, adjustments of TC, TG and HDL-c eliminated the association between HOMA-β and betatrophin. Conclusions Pregnant women have significantly higher betatrophin levels in comparison to unpregnant women. Betatrophin levels are positively and significantly associated with β cell function and lipid levels. Furthermore, lipids may contribute to the association between betatrophin and β cell function.

Resumo Introdução Betatrofina tem sido relacionada à expansão de células β em estado de resistência à insulina. A gravidez é um conhecido estado fisiológico de resistência à insulina. Níveis de betatrofina em gestantes e sua relação com variáveis metabólicas ainda precisam ser esclarecidas. Métodos Um total de 49 gestantes e 31 não gestantes de mesma idade com níveis normais de glicose (UP-NGR) foram incluídas. Dentre elas, de acordo com os resultados da curva glicêmica, base em 75 g, 22 mulheres foram diagnosticadas com diabetes mellitus gestational ( DMG ). Resultados Nosso estudo identificou que gestantes, independente de seus níveis de glicose, tiveram notáveis níveis elevados de triglicerídeos (TG), colesterol (TC), insulina em jejum (FINS), HOMA-IR e HOMA-β. Contudo, pacientes com DMG tiveram bem menos HOMA-β se comparadas às gestantes com níveis normais de glicose ( P-NGR ). Participantes do grupo P-NGR tiveram níveis de betatrofina quase quarto vezes maiores ao das participantes do grupo UP-NGR. Embora os níveis de betatrofina sejam menores no grupo DMG do que no P-NGR, a diferença não obteve significância estatística. Análise da correlação de Spearman demonstrou que os níveis de betatrofina foram positiva e significativamente associados ao TC, TG, HDL-c (high-density lipoprotein cholesterol), FINS e HOMA-β. Contudo, ajustes em TC, TG e HDL-c eliminaram a associação entre HOMA-β e betatrofina. Conclusões Gestantes têm níveis de betatrofina significativamente maiores do que não gestantes. Níveis de betatrofina são positive e significativamente associados às células β funcionais e níveis de lipídeos. Além disso, lipídeos podem contribuir na associação entre betatrofina e células β funcionais.

Comparação da acurácia de preditores de mortalidade na pneumonia associada à ventilação mecânica / Comparing the accuracy of predictors of mortality in ventilator-associated pneumonia

OBJETIVO: Níveis de procalcitonina, midregional pro-atrial natriuretic peptide (MR-proANP, pró-peptídeo natriurético atrial midregional),, C-terminal provasopressin (copeptina), proteína C reativa (CRP) e escore do Sequential Organ Failure Assessment (SOFA) são associados a gravidade e descritos como preditores de desfechos na pneumonia associada a ventilação mecânica (PAVM). Este estudo procurou comparar o valor preditivo de mortalidade desses biomarcadores na PAVM. MÉTODOS: Estudo observacional com 71 pacientes com PAVM. Níveis de procalcitonina, MR-proANP, copeptina e PCR, bem como escore de SOFA foram obtidos no dia do diagnóstico de PAVM, designado dia zero (D0), e no quarto dia de tratamento (D4) Os pacientes receberam tratamento antimicrobiano empírico, com modificações baseadas nos resultados de cultura. Os pacientes que morreram antes de D28 foram classificados como não sobreviventes. RESULTADOS: Dos 71 pacientes, 45 sobreviveram. Dos 45 sobreviventes, 35 (77,8 por cento) receberam tratamento antimicrobiano adequado, comparados com 18 (69,2 por cento) dos 26 não sobreviventes (p = 0,57). Os sobreviventes apresentaram valores significativamente mais baixos em todos os biomarcadores estudados, inclusive no escore de SOFA (exceto PCR) em D0 e D4. Em D0 e D4, a área sob a curva ROC foi maior para procalcitonina. Em D0, MR-proANP teve a maior razão de verossimilhança positiva (2,71) e valor preditivo positivo (0,60), mas a procalcitonina apresentou o maior valor preditivo negativo (0,87). Em D4, a procalcitonina apresentou a maior razão de verossimilhança positiva (3,46), o maior valor preditivo positivo (0,66) e o maior valor preditivo negativo (0,93). CONCLUSIONS: Os biomarcadores procalcitonina, MR-proANP e copeptina podem predizer mortalidade na PAVM, assim como o escore de SOFA. A procalcitonina tem o maior poder preditivo de mortalidade na PAVM.

OBJECTIVE: Levels of procalcitonin, midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal provasopressin (copeptin), and C-reactive protein (CRP), as well as Sequential Organ Failure Assessment (SOFA) scores, are associated with severity and described as predictors of outcome in ventilator-associated pneumonia (VAP). This study sought to compare the predictive value of these biomarkers for mortality in VAP. METHODS: An observational study of 71 patients with VAP. Levels of procalcitonin, MR-proANP, copeptin, and CRP, together with SOFA scores, were determined at VAP onset, designated day 0 (D0), and on day 4 of treatment (D4). Patients received empirical antimicrobial therapy, with modifications based on culture results. Patients who died before D28 were classified as nonsurvivors. RESULTS: Of the 71 patients evaluated, 45 were classified as survivors. Of the 45 survivors, 35 (77.8 percent) received appropriate antimicrobial therapy, compared with 18 (69.2 percent) of the 26 nonsurvivors (p = 0.57). On D0 and D4, the levels of all biomarkers (except CRP), as well as SOFA scores, were lower in eventual survivors than in eventual nonsurvivors. For D0 and D4, the area under the ROC curve was largest for procalcitonin. On D0, MR-proANP had the highest positive likelihood ratio (2.71) and positive predictive value (0.60), but procalcitonin had the highest negative predictive value (0.87). On D4, procalcitonin had the highest positive likelihood ratio (3.46), the highest positive predictive value (0.66), and the highest negative predictive value (0.93). CONCLUSIONS: The biomarkers procalcitonin, MR-proANP, and copeptin can predict mortality in VAP, as can the SOFA score. Procalcitonin alone has the greatest predictive power for such mortality.

Leptina e insulina sérica en adultos con sobrepeso y obesos en régimen hipocalórico con alto contenido de carbohidratos complejos / Serum leptin and insulin in obese adults on hypocaloric dietary regimen of high complex carbohydrate content

En situaciones de cambios en el peso, la evidencia sobre la relación entre la leptina y la insulina con el contenido de grasa corporal no es concluyente. Se planteó establecer asociaciones entre leptina e insulina (ELISA) y pérdida de peso (antropometría) durante un régimen hipocalórico alto en fibra, en 71 individuos (sobrepeso/ obesos), al inicio (I), a dos (2s) y a seis semanas (6s) del régimen. Se aplicaron pruebas no paramétricas para muestras independientes y relacionadas. Hubo disminución significativa de la leptina entre I, 2s y 6s, similar entre sobrepeso y obesidad, normalizándose a las 6s (sobrepeso fueron normales a las 2s y obesos a las 6s). Aumentó la prevalencia de valores normales (leptina <15 ng/mL) durante el régimen. La leptina fue significativamente mayor en obesos que en los con sobrepeso y en mujeres que en hombres, sin diferencias significativas por género para la insulina. Asociación significativa entre leptina e indicadores de adiposidad (índice de masa corporal, circunferencia abdominal). A las 2s, hubo correlación positiva entre leptina e insulina, no evidente a las 6s. El régimen basado en el consumo de fibra fue eficiente para lograr cambios en los parámetros antropométricos y bioquímicos, en especial, una disminución de la leptina.

Leptin acts as a regulatory signal for food intake, body energy balance, body fat content and body weight stability. In order to establish associations among serum leptin, serum insulin and weight loss, 71 obese or overweight adults were assessed by anthropometry and serum determination of leptin at the beginning (B), two weeks (2w) and six weeks (6w) after consuming a dietary regime based on complex carbohydrates intake. Data was analyzed by non parametrical tests for independent and related samples. There was a significant decrease of leptin among B, 2w and 6w of similar nature between overweight and obese participants, with all of them reaching normal values at 6w (overweight at 2w and obese at 6 w). Prevalence of normal leptin values (<15 ng/mL) increased among B, 2w and 6w. Leptin levels were significantly higher in obese vs. overweight and in women vs. men with no differences in serum glucose or insulin by sex. There was a significant association between leptin and adiposity indicators (body mass index and abdominal circumference). At 2w, but not at 6w, a positive correlation between leptin and insulin was found. A dietary regime based on increased consumption of complex carbohydrate (fiber) was efficient to induce favorable changes in anthropometrical and biochemical indicators, especially serum leptin.

Peptide YY, Cholecystokinin, Insulin and Ghrelin Response to Meal did not Change, but Mean Serum Levels of Insulin is Reduced in Children with Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Marked Suppression of Ghrelin Concentration by Insulin in Prader-Willi Syndrome

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.

Insulina, leptina y hormona de crecimiento y su relación con índice de masa corporal e índice de obesidad en adolescentes / Serum Insulin, leptin and growth hormone levels are associated with body mass index and obesity index in adolescents

La leptina, insulina y hormona de crecimiento influyen en la masa grasa, composición corporal y distribución grasa. El propósito de este estudio fue determinar la relación entre los niveles de insulina, leptina y hormona de crecimiento con parámetros antropométricos y lipídicos en adolescentes. Se estudiaron 95 adolescentes entre 13 y 18 años. Se realizó una historia clínico-nutricional donde se midió el índice de masa corporal (IMC) y los pliegues subcutáneos. Se determinaron los niveles basales de glicemia, triglicéridos, colesterol total, HDL-C, LDL-C y VLDL-C, insulina, leptina y hormona de crecimiento. Los niveles de leptina e insulina se relacionaron positivamente con el IMC y el Índice de Obesidad (IOB). La insulina, leptina e indicadores de obesidad se relacionaron en forma negativa con la hormona de crecimiento. El 52% de los adolescentes con IMC≥21,09 Kg/m2 e IOB >42,02 mm se consideraron metabólicamente obesos, debido a que comparados con los adolescentes normales, presentaron niveles elevados de insulina (18,68± 1,52 vs 10,08± 0,38 m U/ml), HOMA IR (3,34± 0,24 vs 1,76± 0,07), leptina (16,30± 1,24 vs 8,11± 1,32 ng/dl) y triglicéridos (78,56± 4,38 vs 64,39± 5,48 mg/dl) y disminución de HDL-C (39,09± 1,27 vs 43,30± 2,38 mg/dl). Estas mismas alteraciones se observaron en adolescentes obesos en quienes se produjo además una disminución significativa de la hormona de crecimiento. Se concluye que en los adolescentes estudiados existió una serie de factores de riesgo como hiperinsulinemia, hiperleptinemia y hormona de crecimiento disminuida relacionada con marcadores de obesidad, alteraciones lipídicas e insulino resistencia, lo cual puede conducir a la aparición temprana de diabetes tipo 2 y enfermedad cardiovascular.

Leptin, insulin and growth hormone levels seem to regulate body composition, fat distribution and fat mass. The purpose of this study was to determine the relationship among insulin, leptin and growth hormone levels in a group of adolescents. Ninety five adolescents (31 boys and 64 girls) between 13 and 18 y. of age were studied. A medical and nutritional history was made which included body mass index (BMI) and subcutaneous skinfolds measurements. Basal levels of glucose, triglycerides, total cholesterol, HDL-C, LDL-C, VLDL-C, leptin, insulin and growth hormone were determined. The leptin and insulin levels were positively associated with body mass index (BMI) and obesity index (OBI). Insulin, leptin and obesity markers were negatively associated with growth hormone level. Fifty two percent of the adolescents with BMI ≥21.09 kg/m2 were considered metabolically obese because they had elevated levels of insulin (18.68 ± 1.52 vs. 10.08 ± 0.38 m U/ml), HOMA IR (3.34± 0.24 vs. 1.76± 0.07), leptin (16.30± 1.24 vs. 8.11± 1.32 ng./dl) and triglycerides (78.56± 4.38 vs 64.39± 5.48 mg/dl) and lower levels of HDL-C (39.09± 1.27 vs 43.30± 2.38 mg/dl), compared with normal group. The same alterations were observed in the obese group, in which significative decrease in growth hormone level was added. We conclude that hyperinsulinemia, hyperleptinemia and low growth hormone levels, may be established as risk factors related to obesity markers, lipid alterations and insulin resistance that can lead to an early development of Type II diabetes and cardiovascular disease.

Ghrelin; Influences on Helicobacter pylori-associated Gastric Diseases / 대한소화기학회지

Recently, gastric Helicobacter pylori (H. pylori) colonization has been shown to affect the expression of leptin and ghrelin, hormones that control appetite and satiety. Gastric leptin, produced by chief and parietal cells and released in response to meals, may play a role in weight gain after eradication of H. pylori infection, whereas ghrelin, produced by X/A-like enteroendocrine cells in oxyntic gland, is released during fasting, and suppressed by feeding and leptin. Whether either that H. pylori genes represent microbial contributions to the complement of thrifty genes of humans, or that H. pylori disappearance plays a role in adiposity remains to be determined. Simply, ghrelin-leptin might tango in body weight regulation, gastric inflammation, and gastric motility. In the current review about the possible role of ghrelin in gastric inflammation, we found that high serum albumin condition decreased ghrelin expression, whereas serum albumin deprivation significantly increased ghrelin expression, however, of which regulation was abolished after H. pylori infection. Ghrelin significantly attenuated the inflammatory stimuli imposed after H. pylori, shown with inactivation of phospho-extracellular signal-regulated kinase (p-ERK) and nuclear factor-KappaB (NF-KappaB)-DNA binding activities. Conclusively, besides orexigenic and weight gaining actions of gastric hormone, ghrelin, it likely endows the stomach the protective effect from exogenous damages.

Plasma Ghrelin level; anorexigenic and orexigenic mediators in patients with end stage renal failure on hemodialysis

Anorexia-associated malnutrition is a severe complication that increases mortality in hemodialysis [HD] patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 22 HD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [NO3] and anorexigens [cholecystokinin [CCK], leptin, glucose-dependent insulinotropic peptide [GIP]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale [VAS]. The patients were divided into three groups: those with anorexia [n = 8], those with obesity associated with high intake [n = 5], and those with no eating behavior disorders [n = 9]. A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high [4101 +/- 1233 mg/mL], with the patients showing values above the control group range [1920 +/- 451mg/mL]. Patients with anorexia had lower ghrelin level and higher CCK and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin [r = 0.43, p < 0.05], growth hormone [r=0.66, p < 0.01], NO3 [r = 0.36, p < 0.05], and eating motivation [VAS]. At the same time, negative relationships were observed between blood ghrelin and GIP [r = -0.42, p < 0.05], insulin [r = -0.4, p < 0.05], and leptin [r = -0.45, p < 0.05]. Ghrelin levels were not related to levels of CCK. Ghrelin plasma levels are elevated in HD patients. Uremic patients with anorexia show relatively lower ghrelin plasma levels than the levels seen in obese patients or in patients with normal appetite. The role of ghrelin in appetite modulation is altered in uremic HD patients, and that alteration is possibly associated with disorders in insulin and growth hormone metabolism

Concentraciones plasmáticas de adiponectina en individuos normales y obesos correlacionadas con el perfil de lípidos plasmáticos / Plasma adiponectin concentration in normal weight and obese individual is associated with profile of plasma lipids

La adiponectina es una proteína del tejido adiposo que mejora la sensibilidad a la insulina y posee propiedades antiaterogénicas. Los niveles circulantes son más bajos en hombres que en mujeres y se encuentran disminuidos en la obesidad, diabetes tipo 2 y enfermedad cardiovascular. Este estudio investiga la relación entre los niveles de adiponectina con los líquidos plasmáticos y la resistencia a la insulina, en 180 individuos normales y obesos. Medimos adiponectina, mediante radioinmunoanálisis, colesterol total sérico, colesterol de HDL (C-HDL), triglicéricos, glicemia de ayuno e insulina plasmática. Las mujeres tenían la adiponectina más alta que los hombres (8,45 ± 3,82 versus 6,10 ± 2,62) y la resistencia a la insulina medida por HOMA IR se correlacionó negativamente con la adiponectina tanto en obesos como en no obesos, independientemente del índice de masa corporal (IMC). Asimismo, hubo una correlación positiva entre adiponectina y C-HDL (p = 0,01) y negativa con los triglicéridos (p = 0,05). Estos resultados indican que los niveles elevados de triglicéridos y los bajos niveles de C-HDL se asocian con concentraciones plasmáticas disminuidas de adiponectina. Se requieren mayores estudios para determinar si la adiponectina es la causante de estas anormalidades lipídicas.