Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity.

Background: Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. Objectives: To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements. Methods: Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ2-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at p < 0.05. Results: Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87% in the VLCKD group and -1.87 ± 2.4% in the LC group (p < 0.001). Mean reductions in VAT were -32.0 cm2 for VLCKD group and -12.58 cm2 for LC group (p < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; p < 0.005). Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04322110.

Comparison of two dose regimens of growth hormone (GH) with different target IGF-1 levels on glucose metabolism, lipid profile, cardiovascular function and anthropometric parameters in gh-deficient adults.

OBJECTIVE: To compare the effects of two regimens of GH therapy with different target IGF-1 levels on anthropometric parameters, glucose metabolism, lipid profile and cardiac function in adults with GH deficiency (GHD). PATIENTS AND METHODS: Retrospective analysis of 14 GHD adults from Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, who were treated with a GH regimen aimed at maintaining serum IGF-1 levels between the median and upper reference limit (high dose group - HDGH) and 18 GHD adults from Federal University Hospital, Curitiba, Brazil, who received a fixed GH dose of 0.2mg/day in the first year of treatment, followed by titration to maintain serum IGF-1 levels between the median and lower reference limit (low dose group - LDGH). All patients were followed for 2 years with analysis of anthropometric parameters, serum levels of IGF-1, glucose, insulin, HOMA-IR, lipid profile, and transthoracic echocardiography. RESULTS: Changes on weight, BMI and waist circumference were similar between the two groups. Insulin levels increased and HOMA-IR worsened in the LDGH group at 1year and improved thereafter. Total cholesterol and triglycerides did not change with therapy. LDL cholesterol reduced in both groups, while HDL-cholesterol significantly increased only in the HDGH group (p=0.007 vs LDGH). No significant variations on echocardiographic parameters were observed. CONCLUSION: The HDGH and LDGH regimens resulted in similar changes on anthropometric, echocardiographic, glucose and lipid parameters in GHD adults, except for increase in HDL cholesterol that was only observed in the HDGH regimen.

Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged men.

OBJECTIVE: To investigate the growth hormone (GH) response to glucagon stimulation test (GST) in a population of healthy men over 50 years old in comparison to insulin tolerance test (ITT), analysis of the spontaneous 24-hour GH profile and insulin-like growth factor 1 (IGF-I). METHODS: 27 healthy men aged between 51 and 65 years were tested. RESULTS: Using non-parametric correlation analysis, a positive correlation between GH peak after GST and mean IGF-I (r = 0.528; p = 0.005) was found, as well with GH peak in 24-hour profile (r = 0.494; p = 0.009). No correlation was found comparing GH peak after ITT with the same parameters. Ten subjects presented GH peak of less than 3.0 microg/L after GST, none confirmed in ITT. CONCLUSIONS: GH peak response to GST was lower than ITT, but it showed a positive correlation with mean IGF-I and also with GH peak in 24-hour profile. However, GST should not be used to differentiate organic growth hormone deficiency (GDH) from the expected decline on GH secretion due to aging.

Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged men / Secreção do hormônio do crescimento em resposta ao teste de estímulo com glucagon em homens saudáveis de meia-idade

OBJECTIVE: To investigate the growth hormone (GH) response to glucagon stimulation test (GST) in a population of healthy men over 50 years old in comparison to insulin tolerance test (ITT), analysis of the spontaneous 24-hour GH profile and insulin-like growth factor 1 (IGF-I). METHODS: 27 healthy men aged between 51 and 65 years were tested. RESULTS: Using non-parametric correlation analysis, a positive correlation between GH peak after GST and mean IGF-I (r = 0.528; p = 0.005) was found, as well with GH peak in 24-hour profile (r = 0.494; p = 0.009). No correlation was found comparing GH peak after ITT with the same parameters. Ten subjects presented GH peak of less than 3.0 μg/L after GST, none confirmed in ITT. CONCLUSIONS: GH peak response to GST was lower than ITT, but it showed a positive correlation with mean IGF-I and also with GH peak in 24-hour profile. However, GST should not be used to differentiate organic growth hormone deficiency (GDH) from the expected decline on GH secretion due to aging.

OBJETIVO: Investigar a resposta do hormônio do crescimento (GH) ao teste de estímulo com glucagon (GST) numa população de homens saudáveis acima dos 50 anos de idade, em comparação ao teste de tolerância à insulina (ITT), além da análise do perfil de secreção espontânea de GH nas 24 horas e fator de crescimento semelhante à insulina (IGF-I) basal. MÉTODOS: 27 homens, com idades entre 51 e 65 anos, foram submetidos aos testes. RESULTADOS: Utilizando análise de correlação não paramétrica, encontrou-se correlação positiva entre o pico de GH pós-GST e a média de IGF-I (r = 0,528; p = 0,005), e também com o pico espontâneo do GH no perfil de 24 horas (r = 0,494; p = 0,009). Não houve correlação do pico de GH pós-ITT com os mesmos parâmetros. Dez indivíduos apresentaram pico de GH após GST inferior a 3,0 μg/L, sem confirmação no ITT. CONCLUSÕES: O pico de GH pós-GST foi menor do que o obtido pós-ITT, porém demonstrou correlação positiva com a média de IGF-I e o pico de GH na secreção espontânea de 24 horas. Entretanto, o GST não demonstrou ser um bom teste para distinguir entre deficiência de hormônio de crescimento (DGH) e somatopausa.

Effects of 5 years of growth hormone (GH) replacement therapy on cardiac parameters and physical performance in adults with GH deficiency.

The purpose of this study was to evaluate the effects of 5 years of GH substitution on cardiac structure and function, physical work capacity and blood pressure levels in adults with GH deficiency (GHD). Fourteen patients were clinically assessed every 3 months for 5 years. Transthoracic echocardiography and exercise test were performed at baseline, 24, 48 and 60 months. Blood pressure (BP) was measured by means of ambulatory monitoring of blood pressure at baseline, 6, 12, 24 and 60 months. Left ventricular mass and its index increased progressively during the 5 years of GH substitution (P = 0.008 and 0.007, respectively). There were no significant changes in all others cardiac parameters evaluated. It was observed a significant improve in functional capacity (P < 0.001) and maximal oxygen uptake (P = 0.006) during the treatment. Diurnal systolic BP increased by 15 mmHg (P = 0.024) and diurnal diastolic BP by 4.5 mmHg (P = 0.037). There was no change in dirnal systolic pressure load but a considerable but non-statistically significant reduction in diurnal diastolic pressure load was observed during the study. During the night diastolic BP increased by 4 mmHg (P = 0.012) despite a substantial but non-statistically significant reduction in diastolic pressure load. We observed an increase in the proportion of persons with a non-physiological nocturnal fall (non-dippers) throughout the study (from 36.4% at baseline to 54.6% after 60 months of therapy). We concluded that 5 years of GH replacement promoted positive effects on exercise capacity and maximum oxygen uptake in spite of a modest increase in BP levels and left ventricular mass. Continuous monitoring is mandatory to arrive at further conclusions concerning the effects of GH substitution in adults on cardiovascular parameters with respect to possible unfavorable long term effects.

Impact of 5 years of growth hormone replacement therapy on cardiovascular risk factors in growth hormone-deficient adults.

The benefits of long-term effects of growth hormone (GH) substitution on carbohydrate and lipid metabolism in GH-deficient (GHD) adults are still controversial. The purpose of this study was to evaluate the effects of 5 years of GH substitution on body composition, glucose and lipid metabolism, and carotid artery intima-media thickness (IMT) in GHD adults. Fourteen patients were clinically assessed every 3 months for 5 years. Serum insulin-like growth factor 1 levels, lipid profile, oral glucose tolerance test, and ultrasonography of the carotid arteries were performed at baseline, 6 months, and every year during replacement. Visceral fat was measured by computed tomographic scan at baseline and at 6, 12, 24, and 60 months. The waist circumference was reduced after 6 months but increased during the next months toward baseline values. Visceral fat decreased during the study. Fasting glucose and insulin levels did not change, as well as the homeostasis model assessment of insulin resistance index. Despite an initial increase in frequency of abnormal glucose tolerance, mean 2-hour oral glucose tolerance test glucose levels decreased during the last 2 years. There was an increase in apolipoprotein A-1 levels during the treatment. Apolipoprotein B levels were reduced after 6 months and remained stable thereafter. A reduction in carotid artery IMT was observed during replacement. We concluded that 5 years of GH replacement therapy promoted positive effects on visceral fat, lipid profile, and carotid artery IMT in GHD adults. Long-term therapy improves insulin sensitivity through a reduction in visceral fat, and continuing monitoring is mandatory in terms of glucose metabolism.

Two years of growth hormone replacement therapy in a group of patients with Sheehan's syndrome.

To investigate the effects of GH replacement on lipid profile, carotid artery intima-media thickness (IMT), glucose metabolism and visceral fat in patients with Sheehan's syndrome, ten patients, mean age 44.8+/-9.5 yr, compared with 10 controls matched for age and body mass index were studied. Total cholesterol, Triglycerides (TG), HDL-c, LDL-c, Apolipoprotein A and B (apoA and apoB) and Lipoprotein (a), serum IGF-1, ultrasonography of the carotid arteries, oral glucose tolerance test (OGTT), HOMA insulin resistance index, insulin sensitivity index (ISI)-composite and abdominal CT scan were performed. When compared to a control group, patients presented lower HDL concentrations (p=0.05) and 2-h OGTT insulin levels (p<0.04) and increased TG levels (p<0.04). After 24 months of GH replacement a reduction in the relation ApoB/ApoA (p=0.04) was observed, as well as an increase in HDL (p<0.004). A decrease in carotid artery IMT and in visceral fat over time was found, p<0.03 and p<0.04 respectively, though without any significant differences during post hoc comparisons of means, which may be explained by the small number of cases studied, but there was a tendency, p=0.08 and p=0.09 respectively. The 2-h OGTT insulin levels increased (p<0.02) as well as the prevalence of glucose intolerance (prevalence = 42.8%, p<0.05). GH replacement therapy promoted favorable effects on carotid artery IMT, lipid profile and visceral fat in patients with Sheehan's syndrome. On the other hand, patients developed abnormal glucose tolerance probably due to an increase in insulin resistance, demonstrated by higher insulin levels, despite favorable changes in body composition.

[Lipid profile and alteration of body composition in growth hormone deficient adults]. / Perfil lipídico e composição corporal na deficiência do hormônio de crescimento em adultos.

BACKGROUND: The growth hormone deficiency (GHD) syndrome in adults and the increased associated cardiovascular risk have been extensively studied in recent years. Abnormal body composition with excess of visceral adiposity and adverse lipid profile are important features of this syndrome. Abnormal lipid profile has been described with increased levels of total cholesterol (C), LDL-cholesterol (LDL-C), triglycerides, decreased levels of HDL-cholesterol (HDL-C) and apolipoproteins abnormalities. METHODS: Lipid profile and the amount of visceral adipose tissue were studied in 31 GHD adults compared with a control group of healthy subjects matched for age, gender and body mass index (BMI). Visceral adipose tissue was evaluated by abdominal computed tomography and anthropometric measurements--BMI (kg/m2) and waist circumference (cm). The lipid profile was studied by measurement of C, LDL-C, HDL-C, triglycerides, apolipoproteins A and B, and Lipoprotein (a). RESULTS: The GHD adults showed increased visceral adipose tissue (156.66 +/- 72.72 vs. 113.51 +/- 32.97 cm2, p = 0.049), higher levels of triglycerides (158.58 +/- 80.29 vs. 97.17 +/- 12.37 mg/dl; p = 0.007) and lower HDL- cholesterol (45.41 +/- 13.30 vs. 55.34 +/- 14.31 mg/dl; p = 0.002). There were no differences in others aspects of lipid profile and anthropometric measurements. CONCLUSION: Growth Hormone Deficient adults showed increased visceral adipose tissue, higher levels of triglycerides and lower HDL- cholesterol levels.

Perfil lipídico e composição corporal na deficiência do hormônio de crescimento em adultos / Lipid profile and alteration of body composition in growth hormone deficient adults

OBJETIVO: A síndrome da deficiência de hormônio de crescimento (DGH) no adulto e o conseqüente aumento no risco cardiovascular têm sido bastante estudados nos últimos anos. De grande relevância clínica são as alterações na composição corporal com aumento do tecido adiposo visceral e perfil lipídico adverso. MÉTODOS: Estudou-se o perfil lipídico e o tecido adiposo visceral de 31 adultos com DGH comparado com um grupo controle de indivíduos saudáveis pareados por idade, sexo e índice de massa corporal (IMC). A avaliação da gordura visceral foi feita por tomografia computadorizada de abdome e por medidas antropométricas, através do IMC (Kg/m²) e da medida da cintura (cm). A avaliação do perfil lipídico foi obtida através de dosagens laboratoriais de colesterol (CT), triglicerídeos (TG), HDL, LDL, apolipoproteínas A e B e lipoproteína (a). RESULTADOS: Foi observado aumento do tecido adiposo visceral nos pacientes DGH (156,66 ± 72,72 vs. 113,51 ± 32,97 cm²; p-valor = 0,049), além de aumento nos níveis de TG (158,80 ± 80,29 vs. 97,17 ± 12,37 mg/dl; p-valor = 0,007) e diminuição nos níveis de HDL (45,41 ± 13,30 vs. 55,34 ± 14,31 mg/dl; p-valor = 0,002). Não houve diferença entre os demais parâmetros do perfil lipídico e nas medidas antropométricas. CONCLUSÃO: Adultos deficientes de GH apresentam aumento da adiposidade visceral e aumento das concentrações de TG com diminuição das concentrações de HDL.

Carotid artery intima-media thickness and lipid profile in adults with growth hormone deficiency after long-term growth hormone replacement.

To investigate the effects of growth hormone (GH) replacement on carotid artery intima-media thickness (IMT) and lipid profile, 29 adults with GH deficiency (GHD), mean age 42.5 +/- 10.1 years, were studied and compared with 29 control subjects matched for sex, age, body mass index, and smoking habits. Lipid profile (total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoproteins A and B, and lipoprotein), serum insulin-like growth factor 1 (IGF-1) levels, and ultrasonography of the carotid arteries were performed at baseline and at 6, 12, and 24 months during GH therapy on maintenance dose. At baseline, when compared with the control group, patients presented increased carotid artery IMT (P < .05) and triglyceride levels (P < .001) and lower HDL concentrations (P < .01). In a linear regression analysis, age and known mean duration of GHD were correlated with carotid artery IMT. After 24 months of GH replacement, a reduction in the mean of carotid artery IMT was observed (P < .01). The apolipoprotein B levels decreased significantly after the first 3 months of GH treatment (P < .001) and remained stable thereafter. Women also presented an increase in HDL cholesterol levels (P < .01). No differences were observed in the other lipids measured. Carotid artery IMT at baseline was inversely correlated with the change in carotid artery IMT (Delta = 24 months - baseline), r = 0.63, P < .001. In conclusion, 24 months of GH replacement therapy promoted favorable effects on carotid artery IMT and lipid profile in patients with GHD. Long-term follow-up studies are required to show whether these beneficial effects will result in reduction of morbidity and mortality from vascular disease.

Glucose metabolism and visceral fat in GH deficient adults: 1 year of GH replacement.

The aim of the current study is to evaluate the effects of 12-month growth hormone (GH) replacement on glucose metabolism and visceral fat in 24 adults with GH deficiency (11 men, 13 women, age 41+/-1.9 year, BMI 27+/-1.2 kg/m2. Glucose metabolism was measured in the fasting state by the homeostatic model assessment (HOMA) insulin resistance index and during a standard oral glucose tolerance test (OGTT). Data were analyzed by HOMA and the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan. GH-deficient adults had increased visceral fat (P=0.029) with lower fasting glucose levels (P=0.004) than the control group on baseline evaluation. GH replacement induced deterioration in glucose metabolism, with progressive increment in fasting insulin levels at 6 and 12 months (P=0.024) and in 2-h-OGTT insulin levels at 3, 6 and 12 months (P=0.001). Plasma glucose levels did not change during the study. There was a deterioration in insulin sensitivity index observed by an increase in HOMA-IR (P=0.049) and a reduction in the ISI-composite (P=0.028), both at 12 months of replacement. Visceral fat and waist-to-hip-ratio (WHR) reduced not only at month 6 but also at month 12 (P=0.0001 and 0.023, respectively). In conclusion, 12 months of GH replacement seem to impair glucose homeostasis, despite favorable alterations in body composition.

Glucose metabolism and visceral fat in GH deficient adults: two years of GH-replacement.

The aim of this study was to evaluate the effect of 24 months of growth hormone (GH) replacement on glucose metabolism and visceral fat in 17 adults with GH deficiency: 9 men and 8 women; age 40 +/- 1.8 yr. [range 20-61] and body mass index 25 +/- 0.8 Kg/m2. Glucose metabolism was evaluated by a standard oral glucose tolerance test (OGTT), by the homeostatic model assessment (HOMA) insulin resistance index and by the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan.Twenty-four months of GH replacement induced an increase in the prevalence of abnormal glucose tolerance, with significant progressive increment in 2h-OGTT insulin levels at 3, 12 and 24 months (p = 0.005). Plasma glucose levels and ISI-composite did not alter during the study. HOMA-IR index increased only in the group of patients (n = 8) who had abnormal OGTT at 24 months (p = 0.012). Visceral fat reduced at month 12 and remained decreased until the end of the study (p = 0.009). In conclusion, the present study suggests that adults with GH deficiency after twenty-four months of GH replacement developed abnormal glucose tolerance, probably due to an increase in insulin resistance, associated with higher insulin levels, despite favorable alterations in body composition.

Avaliação do metabolismo glicídicoe da gordura visceral em adultos deficientes de hormônio de crescimento / Evaluation of glucose metabolism and visceral adiposity in growth hormone deficient adults

A síndrome da deficiência de hormõnio de crescimento (DGH) no adulto e o conseqüente aumento no risco cardiovascular têm sido bastante estudados nos últimos anos. Com o objetivo de avaliar as alterações na composição corporal e a presença de resistência à insulina em adultos com DGH, estudamos 27 pacientes comparados a 27 indivíduos saudáveis pareados por idade, sexo e índice de massa corporal, através de tomografia computadorizada de abdomen para medida da gordura visceral e teste de tolerância oral à glicose (TTOG), com curva de glicose e insulina e estimativa da resistência à insulina pelo Homeostasis Model Assessment (HOMA). Observamos, nos pacientes, aumento do tecido adiposo visceral (p= 0,008) sem aumento da freqüência de alterações no TTOG. As glicemias e insulinemias basais e após 2 horas de sobrecarga oral de glicose e as áreas sob as curvas de glicose e insulina foram semelhantes ao grupo controle (p> 0,05). Não houve diferença na sensibilidade à insulina pelo método HOMA (p= 0,989). Houve correlação positiva significativa da medida de gordura visceral nos pacientes com as dosagens de glicemia (r= 0,583; p= 0,001) e insulina (r= 0,728; p= 0,001) após sobrecarga de glicose e as áreas sob a curvas de glicose (r= 0,403; p= 0,040) e insulina (r= 0,713; p= 0,001), porém sem correlação significativa nos controles (r< 0,40; p> 0,05). Em conclusão, não houve alteração significativa no metabolismo glicídico, apesar do aumento da adiposidade visceral observada em adultos DGH.

Alteraçäo da funçäo hipofisária associada a mucocele gigante / Pituitary function change associated with giant mucocele

Este relato mostra o caso de uma paciente com mucocele gigante do seio esfeinodal, apresentando-se como massa intracraniana,, invadindo a tela túrsica e levando à disfunçäo hipofisária com deficiência córtico e somatotrófica. Revendo a literatura, näo foram encontrados casos semelhantes. Desta forma, seräo discutidos alguns relatos de caso de mucoceles que se apresentaram como massa intracraniana e a reversibilidade da funçäo hipofisária após a cirurgia descompressiva.

Doença de Paget com manifestaçöes nos maxilares / Paget's disease with maxillary manifestations

Discutimos um caso incomum de doença de Paget do osso, de apresentação nos maxilares. Esta forma rara de manifestação de uma doença sistêmica levou à dificuldade inicial em estabelecer o diagnóstico, sendo a etiologia firmada apenas pela biópsia da lesão. Utilizamos bisfosfonatos com boa resposta. Ressaltamos no artigo a necessidade do acompanhamento multidisciplinar desses pacientes devido às complicações odontológicas da doença quando localizada nos maxilares.