Glucose alteration and insulin resistance in asymptomatic obese children and adolescents / Alteração de glicose e resistência à insulina em crianças e adolescentes obesos assintomáticos

Abstract Objective Obesity is associated with the abnormal glucose metabolism preceding type 2 diabetes mellitus. Thus, further investigation on the prediction of this lethal outcome must be sought. The objective was the profile glycemic assessment of asymptomatic obese children and adolescents from Salvador, Brazil. Method A fasting venous blood sample was obtained from 90 consecutive obese individuals aged 8-18 years, of both sexes, for laboratory determinations of glycated hemoglobin, basal insulin, and the Homeostasis Model Assessment Insulin Resistance index. The clinical evaluation included weight, height, waist circumference, assessment of pubertal development, and acanthosis nigricans research. The body mass index/age indicator was used for the severity of overweight assessment. Results Glycemic alterations were evidenced clinically and biochemically, although these individuals had no complaints or symptoms related to blood sugar levels. Quantitative and qualitative variables were respectively expressed measures of central tendency/dispersion and simple/relative frequency, using the SPSS, version 20.0. A p-value <0.05 was considered significant. Conclusion Notably, this study found a high prevalence of glucose and insulin disorders in asymptomatic obese children and adolescents.

Resumo Objetivo A obesidade está associada ao metabolismo da glicose anormal que antecede o diabetes mellitus tipo 2. Assim, uma investigação adicional sobre a predição desse resultado letal deve ser antecipada. O objetivo era a avaliação do perfil glicêmico de crianças e adolescentes obesos assintomáticos de Salvador, Brasil. Método Uma amostra de sangue venoso em jejum foi obtida de 90 indivíduos obesos consecutivos entre 8-18 anos, de ambos os sexos, para determinações laboratoriais de hemoglobina glicosilada, insulina basal e Índice do Modelo de Avaliação da Homeostase de Resistência à Insulina (HOMA-IR). A avaliação clínica incluiu peso, estatura, circunferência da cintura, avaliação do desenvolvimento puberal e pesquisa sobre a acantose nigricans. Utilizamos o indicador de índice de massa corporal/idade referente à gravidade da avaliação de sobrepeso. Resultados Alterações glicêmicas foram comprovadas clínica e bioquimicamente, apesar de esses indivíduos não apresentarem queixas ou sintomas relacionados a níveis de açúcar no sangue. Variáveis quantitativas e qualitativas foram, respectivamente, medidas expressas de tendência central/dispersão e amostra/frequência relativa, com o software Pacote Estatístico para as Ciências Sociais, versão 20.0. O valor de p < 0,05 foi considerado significativo. Conclusão Observamos, contudo, alta prevalência de distúrbios de glicose e insulina em crianças e adolescentes obesos assintomáticos.

Hiperinsulinemia y resistencia insulínica en niños de dos escuelas públicas de Oaxaca, México / Hyperinsulinemia and insulin resistance in children

Background: Obesity during childhood is a risk factor for developing cardiovascular diseases during adulthood. Aim: To measure insulin and glucose levels and parameters of insulin resistance in obese, overweight and normal weight Mexican children. Material and Methods: Comparative study of 21 obese children with a body mass index (BMI) over percentile 95, aged 10 ± 1 years (10 males), 14 children aged 10 ± 2 (7 males) with a BMI between percentiles 85 and 94 and 16 children aged 9 ± 2 years (3 males) with a body mass index between percentiles 10 and 84. Body weight, blood pressure and waist circumference were measured and a blood sample was obtained to measure fasting glucose and insulin levels. Homeostasis model of insulin resistance (HOMA) and quantitative insulin sensitivity check index (QUICKI) were calculated. Results: Among obese, overweight and normal weight children, insulin levels were 14.9 (95% CI 10.90-18.99), 7.20 (CI 5.12-9.28) and 4.73 (CI 95% 1.92-7.53) uU/ml, respectively. The figures for HOMA were 3.16 (95% CI 2.20-4.12), 1.49 (95% CI 1.03-1.94) and 0.97 (95% CI 0.35-1.60), respectively. The figures for QUICKI were 0.331 (95% CI 0.319-0.343), 0.371 (95% CI 0.349-0.393) and 0.419 (95% CI 0.391-0.446), respectively. Compared to their normal weight counterparts, the risk of obese children and those with a waist circumference over percentile 90 of having a HOMA over 3.16 was 17 and 10 times higher, respectively. BMI correlated better than waist circumference with insulin levels. Conclusions: Obese children have higher levels of insulin resistance than their normal weight counterparts.

Evaluación de la insulinemia post carga oral de glucosa como método diagnóstico de resistencia a la insulina / Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance

Background: In our country, the assessment of insulin resistance (IR) measuring serum insulin levels at 60 and 120 minutes after a 75 g oral glucose tolerance test (OGTT), is usual. However, there is no information about the distribution of serum insulin levels in the Chilean population. Aim: To assess the distribution of serum insulin levels at 60 and 120 minutes during OGTTs and suggest a statistical cut-off point to estimate the degree of IR. Material and Methods: Retrospective analysis of 1815 OGTTs performed in non-diabetic subjects aged between 18 and 75 years, at a university medical center. HOMA-IR (Homeostasis Model Assessment), insulin sensitivity index of Matsuda (ISI-Composite), and their correlation with serum insulin levels at 60 and 120 minutes were calculated. Results: The 75th percentiles for serum insulin levels at 60 and 120 minutes were 127 and 81 µU/mL, respectively. There was a high correlation between HOMA-IR and ISI-Composite (r = -089, p < 0.001). There was a weaker although significant correlation between HOMA-IR and ISI-Composite and insulin levels at 60 (r = 0.56 and -0.79 respectively, p < 0,001) and 120 minutes (r = 0.54 and -0.75 respectively, p < 0,001). Conclusions: We propose 60 and 120 min serum insulin levels of 130 and 80 µU/mL respectively, as cut-off values for normality during OGTT in Chilean normoglycemic individuals.

Alteraciones metabólicas en hijos de padres con hipertensión arterial / Metabolic abnormalities in young offsprings of parents with essential hypertension

El antecedente familiar de hipertensión arterial en jóvenes sanos se ha asociado a hiperinsulinemia, que a su vez produciría aumento en el cortisol sérico, confluyendo ambos mecanismos en daño endotelial renal con la presencia de microalbuminuria. El objetivo del estudio consistió en evaluar en jóvenes sanos, hijos de hipertensos, la asociación entre los niveles de insulinemia, cortisol sérico y microalbuminuria, debido a su relación con mayor riesgo cardiovascular. Se realizó un trabajo transeccional y correlacional en la ciudad de Santa Fe, incluyendo 145 jóvenes sanos mayores de 18 años de edad, que se asignaron a dos grupos: aquellos con antecedente de primer grado de hipertensión arterial esencial (grupo de estudio) y sin dicho antecedente (grupo control). Se valoraron las concentraciones séricas en ayunas de insulina, cortisol, y los niveles de microalbuminuria en primera orina matutina. La media de edad fue de 20 ± 2.9 años, siendo el 58% mujeres. El grupo de estudio incluyó el 48% (n = 69). El 4.8% presentó insulino-resistencia, 13.8% microalbuminuria y el 52% hipercortisolinemia, no encontrándose diferencias significativas de los niveles séricos de insulina y cortisol, ni de microalbuminuria entre los grupos, así como tampoco correlación entre estas variables. No se encontró asociación entre el antecedente de 1er grado de hipertensión arterial y alteraciones de la homeostasis de insulina o cortisol así como tampoco evidencia de daño endotelial con presencia de microalbuminuria.

The familiar history of hypertension in healthy young offsprings is associated with hyperinsulinemia, which could lead to increased serum cortisol, resulting in renal endothelial damage and the presence of microalbuminuria. The aim of this study was to evaluate, in healthy young offsprings of hypertensive parents, association between insulin levels, serum cortisol and microalbuminuria attending to its relationship with increased cardiovascular risk. We performed a cross-sectional correlational study in Santa Fe, Argentina, including 145 healthy individuals aged over 18 years, allocated to two groups: those with a history of essential hypertensive parents (study group) and those without such history (control group). We evaluated fasting serum insulin, cortisol, and microalbuminuria levels in the first morning urine. The mean age was 20 ± 2.9 years, and 58% were women. The study group included 48% (n = 69) of the sample. 4.8% had insulin resistance, microalbuminuria 13.8% and 52% hipercortisolinemia, with no significant differences in serum insulin, cortisol, or microalbuminuria between groups. No correlation was found between these variables. In this study there was no association between a history of first degree hypertension and impaired insulin or cortisol homoeostasis.

Assessment of the ability of the triglyceride to high density lipoprotein cholesterol ratio to discriminate insulin resistance among Caribbean-born black persons with and without Hispanic ethnicity / Evaluación de la capacidad de la proporción de los triglicéridos en relación con el colesterol de las lipoproteínas de alta densidad para identificar la resistencia a la insulina entre personas negras nacidad en el Caribe con o sin etnicidad Hispánica

OBJECTIVE: The objective of this research was to determine if the triglyceride (TG) to high density lipoprotein (HDL) cholesterol (TG/HDL) ratio has similar utility for discriminating insulin resistance in Caribbean-born black persons with and without Hispanic ethnicity. METHODS: Serum lipids, glucose and insulin were determined and compared for 144 Hispanic blacks and 655 non-Hispanic blacks living in the US Virgin Islands. Area under the receiver operating characteristics (AUROC) curve statistics were used to evaluate the ability of the TG/HDL ratio to discriminate insulin resistance in the two ethnic groups. RESULTS: Hispanic blacks had significantly higher levels of triglycerides and insulin resistance and a lower level of HDL cholesterol than non-Hispanic blacks. The AUROC curve for the ability of the TG/HDL to discriminate insulin resistance was 0.71 (95% CI = 0.62, 0.79) for Hispanic blacks and 0.64 (95% CI = 0.59, 0.69) for non-Hispanic blacks. CONCLUSIONS: Among Caribbean-born black persons living in the US Virgin Islands, the TG/HDL ratio is a useful screening measure for discriminating insulin resistance in those with Hispanic ethnicity but not in those without Hispanic ethnicity.

OBJETIVO: El objetivo de esta investigación fue determinar si la proporción (TG/HDL) de los triglicéridos (TG) con respecto al colesterol de las lipoproteínas de alta densidad (HDL) tiene una utilidad similar a la hora de identificar la resistencia a la insulina en personas negras nacidas en el Caribe, con o sin etnicidad hispánica. MÉTODOS: Se determinaron y compararon la insulina, la glucosa y los lípidos séricos de 144 negros hispánicos y 655 negros no hispánicos residentes en Islas Vírgenes, USA. Las estadísticas del área bajo la curva de las características operativas del receptor (AUROC) se utilizaron para evaluar la capacidad de la proporción TG/HDL para establecer la resistencia a la insulina en los dos grupos étnicos. RESULTADOS: Los negros hispánicos tenían niveles significativamente más altos de triglicéridos y resistencia a la insulina y un menor nivel de colesterol HDL que los negros no hispánicos. La curva AUROC para la capacidad del TG/HDL para establecer la resistencia a la insulina fue 0.71 (95% CI = 0.62, 0.79) para los negros hispánicos y 0.64 (95% CI = 0.59, 0.69) para los negros no hispánicos. CONCLUSIONES: Entre las personas negras que viven en las Islas Vírgenes, la proporción de TG/HDL es una medida útil de tamizaje pata establecer la resistencia a la insulina en las personas de etnia hispana, pero no en las personas de etnicidad no hispánica.

Avaliação do hiperinsulinismo em amostra de crianças pré-puberes / Hyperinsulinism assessment in a sample of prepubescent children

OBJETIVOS: Determinar a relação entre o índice de massa corporal (IMC), o homeostasis model assessment - insulin resistance (HOMA-IR) e a insulinemia. MÉTODOS: Realizou-se um estudo observacional prospectivo transversal com 132 crianças pré-púberes em idade escolar e residentes no município de Santo André (SP). Fez-se a avaliação antropométrica e a mensuração da glicemia, da insulinemia e do índice HOMA-IR. RESULTADOS: Dentre as 132 crianças avaliadas, 78 eram meninas (59,1 por cento) e 54 eram meninos (40,9 por cento), com média de idade de 8,7 anos e média de IMC de 13,7 kg/m². Observou-se uma associação significativa e positiva entre HOMA-IR e IMC, insulina e IMC, peso e HOMA e entre insulina e peso; também foi constatado que, quanto maior for o IMC, maior será o valor de HOMA. CONCLUSÕES: Os resultados do presente estudo permitem concluir que há uma forte associação entre o hiperinsulinismo e a obesidade, devendo ser tomadas algumas medidas para evitar o ganho de peso durante a infância e a adolescência.

OBJECTIVES: To determine the relationship between body mass index (BMI), homeostasis model assessment - insulin resistance (HOMA-IR) and insulinemia. METHODS: This was a prospective cross-sectional observational study of 132 prepubescent schoolchildren residents in the municipality of Santo André, Brazil. Children underwent anthropometric assessment, their glycemia and insulinemia were measured and their HOMA-IR index calculated. RESULTS: Seventy-eight of the 132 children (59.1 percent) were girls and 54 were boys (40.9 percent), with a mean age of 8.7 years and mean BMI of 13.7 kg/m². A significant positive association was detected between HOMA-IR and BMI, insulin and BMI, weight and HOMA and between insulin and weight. It was also found that the higher the BMI, the greater the HOMA score. CONCLUSIONS: The results of this study allow for the conclusion that there is a strong association between hyperinsulinism and obesity. Measures should be taken to avoid weight gain during childhood and adolescence.

Emissões otoacústicas por produtos de distorção em ovinos normais e após indução de hiperinsulinemia / Distortion product otoacoustic emissions in sheep before and after hyperinsulinemia induction

As emissões otoacústicas transientes evocadas e as emissões otoacústicas por produtos de distorção vêm assumindo importância significativa na identificação de alterações cocleares. OBJETIVO: Através da monitorização das emissões otoacústicas, registrar os limiares dos produtos de distorção em condições normais e na presença de modificações eletrofisiológicas nas células ciliadas externas cocleares de ovelhas após a indução de hiperinsulinemia aguda. MATERIAL E MÉTODO: Estudo experimental com sete ovelhas no grupo-controle e sete no grupo-estudo. Os níveis de insulina e glicose foram verificados simultaneamente ao registro das emissões otoacústicas por produtos de distorção de 10 em 10 minutos, até o tempo de 90 minutos. O grupo-controle recebeu soro fisiológico, e o grupo-estudo, injeção em bolo de 0,1 U/kg de insulina humana regular. RESULTADOS: Houve diminuição significante nos limiares dos produtos de distorção no grupo-estudo em relação ao grupo-controle nas freqüências acima de 1.500 Hz e após o tempo de 60 minutos (P < 0,001). CONCLUSÃO: O estudo permitiu estabelecer os limiares das emissões otoacústicas por produtos de distorção em ovelhas com constante reprodutibilidade, o que mostra que o método é adequado para uso em investigações audiológicas e otológicas. Ficou, ainda, plenamente identificado que o hiperinsulinismo agudo foi capaz de provocar relevantes modificações nestes limiares.

Transient evoked otoacoustic emissions and distortion product otoacoustic emissions have gained significant importance in the identification of cochlear alterations. AIM: To record distortion product thresholds through the monitoring of otoacoustic emissions in normal conditions and in the presence of electrophysiologic changes in cochlear outer hair cells in sheep after hyperinsulinemia induction. MATERIAL AND METHODS: Experimental study, with seven sheep in the control group and seven in the study group. Insulin and glucose concentrations were measured simultaneously for the recording of distortion product otoacoustic emission every 10 minutes, all the way to 90 minutes. The control group received saline solution, and the study group received a bolus injection of 0.1 U/kg of regular human insulin. RESULTS: There was a significant reduction in distortion product thresholds in the study group when compared to the control group at frequencies greater than 1,500Hz and after 60 minutes (P < 0.001). CONCLUSION: This study established distortion product otoacoustic emission thresholds in sheep with constant reproducibility, demonstrating that the method is adequate for use in audiology and otology investigations. Results also fully confirm that acute hyperinsulinemia may cause important changes in these thresholds.

Relación entre hiperinsulinemia, disfunción diastólica e hipertrofia del ventrículo izquierdo en pacientes con hipertensión arterial sistémica / Association of hyperinsulinemia with left ventricular hypertrophy and diastolic dysfunction in patients with hypertension

Background: Hypertension is the main independent cardiovascular risk factor. However, there are additional factors that induce organic damage. Aim: To assess the association between hyperinsulinemia, ventricular hypertrophy and left ventricular diastolic function. Patients and Methods: Seventy-four patients aged 30 to 65 years, with mild or moderate systemic hypertension, with overweight or mild obesity and normal glucose tolerance curve (GTC), were studied. Serum insulin was measured during GTC. The maximum levels of insulin and glucose were observed 60 minutes after the oral glucose load and they were expressed as rG/1. Patients were stratified in three groups according to their glucose and insulin fasting levels (I0) and post-glucose challenge levels (rG/I): Group 1 (normoinsulinemic patients) I0 <17 mU/mL and rG/I >2 (2.45+0.4). Group 2 (post-prandial hyperinsulinemic patients) I0 <17 mU/mL and rG/I <2> 1 (1.34+0.3). Group 3 (persistently hyperinsulinemic patients) I0 >17 mU/mL and <1 (0.7+0.3). Left ventricular mass and its diastolic function were measured by Doppler echocardiography. Results: No differences in blood pressure or age were observed between groups. There was a negative correlation between ventricular mass and rG/1 (r =-0.282, p =0.015). Left ventricular diastolic dysfunction was significantly more deteriorated in group 3, as compared with group 1 (p <0.001 ANOVA). There was a significant correlation between g/GI and diastolic dysfunction (r =0.232 p =0.047). Conclusions: Fasting, post challenge hyperinsulinemia and a rG/I <1 are associated with higher ventricular mass and left ventricular diastolic dysfunction, independent of blood pressure and age.

Correlation between change in serum homocysteine levels during hyperinsulinemia and insulin sensitivity.

OBJECTIVE: To study the correlation between the changes in homocysteine (Hcy) levels during hyperinsulinemia and insulin sensitivity. MATERIAL AND METHOD: Forty-five subjects who underwent hyperinsulinemic euglycemic clamp were studied. Twenty-five subjects had normal glucose tolerance, seven had impaired glucose tolerance, and 13 had type 2 diabetes mellitus. Serum Hcy was measured before (Hcy 0) and at 120 minutes (Hcy 120) of glucose clamp. The change in Hcy levels during hyperinsulinemia was expressed as absolute difference between Hcy 0 and Hcy 120 (deltaHcy) and percentage difference over Hcy 0 (%deltaHcy). Insulin sensitivity index (ISI) was used to correlate with variables of interest. RESULTS: The ISI was not correlated with Hcy 0 and Hcy 120 but was correlated with deltaHcy and %deltaHcy. The deltaHcy and %deltaHcy were not significantly different between subjects with normal and abnormal glucose tolerance, whereas they were significantly different between subjects whose ISI were above and below the mean value. CONCLUSION: Although the change in Hcy levels during hyperinsulinemia was correlated with insulin sensitivity, the Hcy levels per se were not found to be correlated with insulin sensitivity. The change in Hcy levels during hyperinsulinemia was significantly different in subjects whose ISI was above and below the mean value but not in subjects with normal and abnormal glucose tolerance. This indicated that insulin resistance, not the glucose tolerance status, affected Hcy metabolism.

Circunferência abdominal como indicador de parâmetros clínicos e laboratoriais ligados à obesidade infanto-juvenil: comparação entre duas referências / Abdominal circumference as an indicator of clinical and laboratory parameters associated with obesity in children and adolescents: comparison between two reference tables

OBJETIVO: Avaliar sensibilidade e especificidade de duas tabelas de referência para circunferência abdominal em crianças na detecção de valores elevados de índice de massa corporal, colesterol total, insulinemia de jejum, leptinemia de jejum e homeostasis model assessment. MÉTODOS: Foram avaliados 624 indivíduos, de ambos os sexos, com idades entre 7 e 18 anos, provenientes de duas escolas públicas, obtendo-se amostra de sangue venoso em jejum para dosagens de insulina, glicemia, leptina e colesterol total. Peso, estatura e circunferência abdominal foram aferidos de acordo com recomendações internacionais. Foram montadas tabelas de contingência em que se compararam, de um lado, a presença ou ausência de aumento na circunferência abdominal segundo os pontos de corte propostos de Taylor et al. e Freedman et al. e, de outro, presença ou ausência de valores alterados dos parâmetros avaliados. RESULTADOS: Os valores de sensibilidade foram sempre superiores para a tabela de Taylor et al., ao contrário da especificidade, sempre mais elevada para a tabela de Freedman et al. Os valores preditivos positivos foram, em geral, bastante baixos, mostrando-se relevantes apenas para o indicador índice de massa corpórea. CONCLUSÕES: Os resultados obtidos apontam para que se considere a referência de Taylor et al. melhor do ponto de vista da triagem, selecionando indivíduos com maior probabilidade de apresentarem as alterações estudadas; por outro lado, a referência de Freedman et al. mostrou-se mais adequada para uso clínico, sendo possível a sua utilização para substituir dosagens que possam não estar ao alcance do profissional, como insulinemia e leptinemia.

OBJECTIVE: To evaluate the sensitivity and specificity of two pediatric abdominal circumference reference tables to detect abnormally high body mass index, total cholesterol, fasting blood insulin and leptin levels, and homeostasis model assessment values. METHODS: A total of 624 male and female subjects, with ages ranging from 7 to 18 years, were evaluated. All children were recruited from two public schools. Venous blood samples were collected for determination of fasting plasma insulin, glucose, leptin, and total cholesterol levels. Weight, height and abdominal circumference were assessed according to internationally accepted guidelines. Contingency tables were constructed, comparing the presence or absence of increased abdominal circumference, according to cutoff points established by Taylor et al. and Freedman et al., with the presence or absence of abnormal values in the laboratory tests. RESULTS: Sensitivity values were consistently higher for the table by Taylor et al., whereas the table by Freedman et al. showed greater specificity. Positive predictive values were quite low in general, and were only relevant for body mass index. CONCLUSIONS: Results indicate that the table by Taylor et al. is best for screening purposes, as it identifies individuals at higher risk of presenting abnormal test results. On the other hand, the reference table by Freedman et al. is more suitable for clinical practice, as it could be used to replace laboratory measurements, such as blood insulin or leptin levels, which may not be available at all sites.

Impact of type 2 diabetes mellitus on cardiac structure and function: the association with microalbuminuria and hyperinsulinemia

Early determination of myocardial manifestations of diabetes mellitus [DM] is of a major importance, since myocardial involvement considerably influence the prognosis of diabetic patients. Microalbuminuria [MA] and hyperinsulinemia [HI] have been shown to predict cardiovascular [CV] disease in patients with DM. However the relationship between these risk factors and both cardiac structure and function is still unclear. To assess the Echocardiographic evidence of cardiomyopathy in asymptomatic patients with type 2 DM; to relate these findings to MA and fasting plasma insulin level [FI]; and to investigate whether these observations are independent of glycemic control and other clinical CV risk factors. 63 type 2 diabetic patients without known cardiac diseases, duration of DM [mean 52.4 +/- 51.4 month], age [47.4 +/- 807 year], body mass index [BMI] [26.6 +/- 3.2], men [41/63], in addition to 20 healthy subjects matched for age, sex and BMI served as control were enrolled in the present study. Based on MA and FI, patients were subgrouped into [microalbuminuric and normoalbuminuric] and [hyperinsulinemic and normoinsulinemic] respectively. We compared Echo- derived indices of left ventricular [LV] structure and LV systolic and diastolic functions in patients versus control subjects and between the different patient subgroups. Diabetic patients had greater LV posterior wall thickness [PWT], interventricular septal thickness [IVST], and LV mass index [LVMI] [p<0.0001 for each]. LV diastolic dysfunction, manifested as reduction in E velocity and E/A ratio and prolongation in isovolumic relaxation time [IVRT] [p<0.001 for each], was documented in diabetic patients as compared with control subjects. MA was diagnosed in 15/63 [24%] patients. As compared with normoalbuminuric patients, MA was associated with higher fasting blood glucose [FBG] and FI [p<0.05 for each], greater LVPWT [p<0.05], and LVMI [p=0.02], and lower fractional shortening [FS], ejection fraction [EF], and E/A ratio [p<0.001, p=0.006 and p<0.05 respectively]. Patients with HI had lower FS [p=0.02] and lower E velocity [p=0.04] than in patients with normal FI. In multi-variate analysis, the associated findings either with MA or FI has been unchanged after adjusting for the duration of DM, glycemic control, age, gender, BMI, and BP. Type 2 diabetic patients without overt heart disease have increased LV wall thickness and LVMI and LV diastolic dysfunction suggesting subclinical diabetic cardiomyopathy [DCM]. MA and HI are independently associated with these changes, which may contribute to the relation of albuminuria and HI with increased rate of CV event among diabetics. Thus, screening of either MA or HI may identify patients at CV high risk

Beneficial effects of Zingiber officinale Roscoe on fructose induced hyperlipidemia and hyperinsulinemia in rats.

Fructose supplementation produced cardinal features of Syndrome-X including significant elevations in seum cholesterol, triglyceride, glucose and insulin and also in body weight. While treatment with methanolic extract of dried rhizomes of Zingiber officinale produced a significant reduction in fructose induced elevation in lipid levels, bodyweight, hyperglycemia and hyperinsulinemia, treatment with ethyl acetate extract of Z officinale did not poduce any significant change in either of the last two parameters. However, it produced a significant reduction in elevated lipid levels and body weight The concentration of 6-gingerol was found to be higher in methanolic extract and less in ethyl acetate extract. The results suggest that the methanolic extract of Z officinale produces better effects as compared to ethyl acetate extract in fructose induced hyperlipidemia associated with insulin resistance. The extent of activity appears to be dependent on the concentration of 6-gingerol present in the extracts.

Lipodistrofia generalizada congênita: correlação com leptina e outros aspectos bioquímicos / Generalized congenital lipodystrophy: correlation with leptin and other biochemical parameters

PURPOSE: To correlate serum leptin and insulin levels, and the glucosic profile of 21 patients shared in diabetics and non diabetics with Congenital Generalized Lipodystrophy (CGL). METHODS: In a prospective study, were dosed serum leptin level with radioimmunoassay technique, fasting plasma glucose through of the glucoseoxidase-peroxidase reaction, the hemoglobin glycate using the technique microchromatography for ionic exchange resin and insulin through immunoassay system. The fructosamine concentration serum was determinated for reduction nitroblue tetrazolium method. The Student's test was used to compare results between the groups and the correlation [quot ]r[quot ] coefficient to analise the relation among the several variants studied, with significant level of 5% (p < 0.05). All the statistical procedures were performed using the Excel by Microsoft and the Statistic program for Windows by StatSoft, Inc. version 5.1 edition 97. RESULTS: Leptin decreased on the most patients, showing no statistically significant difference between the groups. Also there wasn't difference statistically significant (p = 0.9542) of the insulin's value between diabetics and non diabetics. CONCLUSION: The hyperinsulinism and the hypoleptinemia occurred independently of diabetes in the CGL's patients and this can be due to the natural history of disease, in which the raise insulin levels precede the initial diabetes mellitus and the low leptin levels were related to the lipoatrophy.

Polycystic ovarian syndrome and hyperinsulinaemia

To determine the occurrence of hyperinsulinaemia in women with polycystic ovarian syndrome [PCOS]. A descriptive study. Isra University Hospital, Hyderabad from January 2002 to December 2003. Total 64 subjects were recruited from gynaecological outpatients department, between the ages of 15 and 40 years with clinical diagnosis of polycystic ovarian syndrome, presenting with weight gain, oligomenorrhoea, secondary amenorrhoea, hirsuitism or infertility and either ultrasound evidence of PCOS or raised Leutinizing Hormone [LH]/ Follicular Stimulating Hormone [FSH] ratio. Patient's venous blood was checked for fasting serum insulin. Out of total 64 women selected, 37[57.81%] were between 21 - 30 years of age. Weight gain was the commonest presenting complain [84.37%] followed by oligomenorrhoea [79.68%]. Infertility was found in 46 women [71.87%] and hyperandrogenism was observed in 43 women [62.49%]. Thirty-nine women [60.93%] had ultrasound evidence of PCOS and 43 [67.18%] had LH / FSH ratio greater than 2:1. Hyperinsulinaemia was seen in 27 [42.19%] women. In this study, 27 women [42.19%] had hyperinsulinaemia which indicates significant insulin resistance. Thus, all the patients presenting with clinical or biochemical evidence of PCOS must undergo checking of fasting serum insulin levels

Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome

The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS) are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH) and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years) were treated with metformin (500 mg three times daily) for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women) and PCOS women during the late follicular (one sample) and luteal (3 samples) phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA), Duncan's test and Karl Pearson's coefficient of correlation (r). The endocrine study showed low progesterone level (4.9 ng/ml) during luteal phase in the PCOS women as compared with control (21.6 ng/ml). A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01) and between progesterone and LH (r = -0.56; P < 0.05) concentrations, and a positive correlation (r = 0.83; P < 0.001) was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml) in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.

Insulin autoimmune syndrome: case report

CONTEXTO: A síndrome da hiperinsulinemia autoimune (SHA, doença de Hirata) é uma causa rara de hipoglicemia nos países ocidentais. Ela é caracterizada por episódios de hipoglicemia, níveis elevados de insulina e presença de anticorpos anti-insulina. Nosso objetivo é relatar um caso da SIA identificado na América do Sul. RELATO DO CASO: Um homem caucasiano de 56 anos de idade começou a apresentar sintomas neuroglicopênicos durante hospitalização devida a trauma grave. A avaliação laboratorial confirmou hipoglicemia e níveis extremamente elevados de insulina. Os exames radiológicos convencionais realizados foram negativos para tumor pancreático. A remissão clínica da doença não ocorreu durante o uso de verapamil e corticóides. Desta forma, pancreatectomia subtotal foi realizada devido à ausência de resposta ao tratamento conservador e à impossibilidade de serem utilizados imunosupressores em razão da bacteremia persistente. O exame histopatológico revelou hiperplasia difusa de células beta. O paciente persiste apresentando níveis elevados de insulina porém praticamente não apresenta mais episódios de hipoglicemia.

Effect of some hypolipidemic drugs on glycemic control, lipid profile and some oxidative indiced in experimental hyperlpidemic diabetic rats

Diabetic patients, especially those with type-2 diabetes, are at a higher risk of developing cardiovascular disease. The specific pattern of diabetic dyslipidaemia, hyperglycemia, hyperinsulinemia, increased oxidative stress and inflammatory cytokines are co-operative factors for increasing cardiovascular morbidity and mortality in these patients. The present study was conducted to investigate the impact of different antidyslipidemic agents on these risk factors in a rat model of diabetic dyslipidaemia with hyperinsulinemia. A total of 70 rats were involved in the study; 10 of which served as a normal control group. The remaining rats were lipid-fed and streptozotocin [STZ]-injected, and were randomly assigned to no treatment [control group] or to 2-month treatment with pravastatin, fenofibrate, cholestyramine, nicotinic acid or fish oil. The lipid-fed STZ-injected rats developed high fasting serum glucose and glycated hemoglobin [HbAlc] levels together with hyperinsulinemia. They also acquired the characteristic pattern of diabetic dyslipidemia, i.e. increased levels of low density lipoprotein-cholesterol [LDL-C] and triglycerides [TG], and decreased high density lipoprotein-cholesterol [HDL-C] level. This was associated with increased markers of oxidative stress and inflammation "increased serum levels of malondialdehyde [MDA] and tumor necrosis factor-alpha [TNF-c_ together with decreased concentration of reduced glutathione and superoxide dismutase [SOD] activity in liver and kidney' Both pravastatin and fenofibrate significantly decreased serum cholesterol, LDL-C and TG, and increased serum HDL-C. However, only fenofibrate could normalize serum levels of HDL-C and TG. Cholestyramine significantly decreased serum levels of total cholesterol and LDL-C but increased the serum level of TG. Nicotinic acid produced significant decreases in serum TG and LDL-C levels and a significant increase in serum HDL-C level. Fish oil only significantly decreased the serum TG level. Fenofibrate and fish oil produced significant decreases in serum glucose, HbAJc and serum insulin levels. Pravastatin only decreased serum insulin level significantly. Cholestyramine did not affect the glycemic control, Nicotinic acid, on the other hand, produced significant increases in serum glucose, HbAlc and serum insulin levels. .Pravastatin, fenofibrate and fish oil decreased the oxidative stress and serum level of TNF-a. On the other hand, cholestyramine and nicotinic acid did not significantly change any of the studied oxidative and inflammatory parameters. Major outcome clinical studies are required to compare the effect of the most promising agents, pravastatin, fenofibrte, fish oil and/or their possible combinations on the overall mortality and morbidity in diabetic dyslipidemic patients

New biochemical markers in chronic heart failure

We investigated the plasma levels of tumour necrosis factor-alpha [TNF-alpha], leptin and insulin, and their relation to body mass index [BMI] in 80 male patients who presented with chronic heart failure [mean age: 47 +/- 4 years] at Tanta University Hospital. Plasma leptin, TNF-alpha and insulin were significantly increased and BMI significantly decreased in New York Heart Association classes III and IV patients. TNF-alpha, leptin and insulin were positively correlated, and TNF-alpha and BMI and leptin and BMI were negatively correlated in stages III and IV of heart failure. We conclude that cytokine neuroendocrine activation may form part of advanced stage heart failure. It may also be responsible for worsening cachexia, and can be used as a marker to determine disease severity

Serum leptin concentrations in hyperinsulinemia in the sets of obese, lipodystrophic and/or non-obese patients.

OBJECTIVE: To study the relationship between serum leptin and circulating insulin under basal and in response to oral glucose administration in hyperinsulinemic patients with or without obesity. MATERIAL AND METHOD: Fifteen female patients of known hyperinsulinemia provided material for the study. Leptin and insulin in sera were estimated by radioimmunoassay methods. RESULTS: Eight of the 15 hyperinsulinemic patients with high body mass index (BMI) (31 +/- 0.94 kg/m2) had significantly (p < 0.01) elevated serum leptin concentrations (26.1 +/- 2 ng/ml) as compared to the levels in the remaining seven non-obese hyperinsulinemic patients with BMI of 20 +/- 1.0 kg/m2; their mean levels of serum leptin were low 5.7 +/- 1.1 ng/ml. Four of the latter group had face-sparing partial lipodystrophy. The mean circulating leptin concentrations in the control group of seven healthy normoinsulinemic and regularly menstruating women with normal BMI (19 +/- 0.95 kg/m2) were 13.7 +/- 1.8 ng/ml. DISCUSSION: The results of the present study in 15 hyperinsulinemic patients show that circulating levels of leptin are not related to serum insulin. However, there was a positive correlation with BMI. An interesting observation of the study is that, notwithstanding the normal BMI, the group of hyperinsulinemic patients with face-sparing partial lipodystrophy had the lowest levels of circulating leptin concentrations. They were closer to the values found in prepubertal girls.

Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic Beta-cell demand in men

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic ß-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic ß-cell secretion in men with different body compositions. Eighteen young men (30.0 ± 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P<0.05), proinsulin (r = -0.47, P<0.05), C-peptide (r = -0.55, P<0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P<0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P<0.05). When subjects were divided into obese (BMI >28 kg/m2, N = 8) and nonobese (BMI £25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic ß-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic ß-cell demand