Prevalencia de hiperinsulinismo patológico post carga de glucosa y su relación con factores de riesgo cardiovascular, en adultos no diabéticos con insulinemia basal normal / Prevalence of pathologic hyperinsulinism after a glucose load charge: its relation to cardiovascular risk factors

Introducción: 25% de personas con hiperinsulinismo desarrolla diabetes 3-5 años luego del primer diagnóstico y 70% lo hará en el resto de la vida. Intervenir los niveles de glicemia desde que se detecta hiperinsulinemia evita la progresión a diabetes y restaura el metabolismo glicémico. Objetivos: Determinar la prevalencia de hiperinsulinismo patológico post-carga de glucosa (HPPG) y su relación con factores de riesgo cardiovascular en adultos 100 UI/ml a las 2 horas), sexo, hipertensión arterial, dislipidemia, malnutrición por exceso, sedentarismo, tabaquismo, ateromatosis e infarto miocárdico documentado. Con STATA 17 se calculó la prevalencia de variables en población general y según categoría de HPPG y se evaluó la significancia con prueba exacta de Fisher. Se compararon medias con ANOVA y t-test con nivel de significancia <0,05. Se usó regresión binomial para estimar Razón de Prevalencia e intervalos de confianza en variables cuantitativas y cualitativas. Resultados: la prevalencia de HPPG fue 41%. La edad promedio 37,5 años, el sexo masculino 52,9%, la hipertensión-arterial 40,5% y la dislipidemia 74,4%. Al comparar las poblaciones con y sin HPPG existieron diferencia estadísticamente significativa en las variables dislipidemia, hipertensión-arterial, malnutrición por exceso y sexo-masculino. La razón de prevalencia alcanzó a un 62%, 37%, 59% y 20% respectivamente. Conclusión: Se encontró una alta prevalencia de HPPG. Los factores de riesgo asociados a ella fueron dislipidemia, hipertensión arterial, malnutrición por exceso y sexo masculino. Esto sugiere que encontrar HPPG puede ser de utilidad para detectar precozmente a la población con un mayor riesgo de enfermedad cardiovascular.

Introduction: 25% of people with hyperinsulinism develop diabetes 3-5 years after the first diagnosis and 70% will do so in the rest of their lives. To control glycemia levels as soon as hyperinsulinemia is detected, progression to diabetes is prevented and glycemic metabolism is restored. Aim: To determine the prevalence of post-glucose load pathological hyperinsulinism (HPPG) and its relationship with cardiovascular risk factors in adults 100 uIU/ ml at 2 hours), sex, hypertension, dyslipidemia, excess malnutrition due to, sedentary lifestyle, smoking, documented atheromatosis and myocardial infarction. The prevalence of variables in the general population was calculated and, in relation to the HPPG category, significance is evaluated with Fisher's exact test. Finally means are compared with ANOVA and t-test. With significance level <0.05. Binomial regression was used to estimate the prevalence ratio and confidence intervals in quantitative and qualitative variables. Statistical analysis was performed with the STATA 17 software. Results: HPPG prevalence was 41%, mean age 37.5 years, male sex 52.9%, arterial hypertension 40.5% and dyslipidemia 74.4%. Un relation to the presence of HPPG a statistically significant difference in the variables dyslipidemia, arterial hypertension, malnutrition due to excess and male sex was found. The prevalence ratios were 62%, 37%, 59% and 20%, respectively. Conclusion: A high prevalence of HPPG was found. Risk factors associated to HPPG were dyslipidemia, arterial hypertension, malnutrition due to excess and male sex. Thus, HPPG can play a role in the early detection of a higher risk of cardiovascular disease in the general population.

Insulinoma simulando una epilepsia: reporte de caso / Insulinoma simulating epilepsy: case report

Insulinoma es un tumor neuroendocrino que surge de las células ß del páncreas y produce hiperinsulinemia endógena. Son neoplasias raras con una incidencia reportada de 4 casos por millón de habitantes por año. La presentación clínica típicamente cursa con síntomas adrenérgicos y neuroglucopénicos secundarios a hipoglicemia. Requiere estudios de niveles séricos de insulina, pro-insulina y péptido C, además de imágenes diagnosticas que confirmen los hallazgos. La mayoría de los insulinomas son benignos, su sitio primario más común es el páncreas y pueden extirparse quirúrgicamente. Se presenta el caso de un hombre de 36 años con déficit cognitivo leve y episodios de diaforesis con deterioro neurológico hasta convulsiones tónico clónicas generalizadas que curiosamente resolvían con uso doméstico de "panela molida". Se ingresó a urgencias por ataques recurrentes de hipoglicemia severa con requerimiento de altas dosis de dextrosa al 50% por acceso central, hasta confirmación diagnóstica, intervención y resección de tumor neuroendocrino pancreático bien diferenciado (G1 según clasificación OMS) tipo insulinoma en la cola del páncreas.

Insulinoma is a neuroendocrine tumor that arises from the ß cells of the pancreas and produces endogenous hyperinsulinemia. They are rare neoplasms with a reported incidence to 4 cases per million inhabitants per year. The clinical presentation typically presents with adrenergic and neuroglycopenic symptoms secondary to hypoglycemia. It requires studies of serum levels of insulin, pro-insulin and C-peptide, in addition to diagnostic images that confirm the findings. Most insulinomas are benign, their most common primary site is the pancreas, and they can be removed surgically. We present the case of a 36-year-old man with mild cognitive deficits and episodes of diaphoresis with neurological deterioration to generalized clonic tonic seizures that curiously resolved with domestic use of "ground brown sugar". He was admitted to the emergency department due to recurrent attacks of severe hypoglycemia with a high-dose requirement for 50% dextrose through central access, until diagnostic confirmation, intervention, and resection of a welldifferentiated pancreatic neuroendocrine tumor (G1 according to WHO classification) insulinoma in the tail of pancreas.

Obesidade na infância e adolescência / Obesity in childhood and adolescence

A obesidade é uma doença crônica e multifatorial com sérias repercussões na saúde. O excesso de peso na infância aumenta o risco de obesidade na adolescência e na vida adulta. A obesidade é uma das principais causas de hipertensão arterial em crianças e adolescentes. No sexo feminino, os problemas ginecológicos relacionados com a obesidade incluem as desordens menstruais e a diminuição da fertilidade na adolescência e na vida adulta. O controle dessa patologia evita a sua evolução para formas crônicas e graves, que acarretaria novos transtornos e consequências para essas jovens. A mudança de hábitos alimentares e a realização de atividade física são a principal linha de tratamento. O tratamento medicamentoso é reservado para portadoras de obesidade grave que apresentam comorbidades associadas e que não respondem às mudanças do estilo de vida. (AU)

Obesity is a chronic and multifactorial disease with serious repercussions on health. Overweight in childhood increases the risk of obesity in adolescence and adulthood. Obesity is one of the main causes of high blood pressure in children and adolescents, among others. In women, gynecological problems related to obesity include menstrual disorders and decreased fertility in adolescence and adulthood. The control of this pathology prevents its evolution to chronic and severe forms that would cause new disorders and consequences for these young women. The main line of treatment is to change eating habits and encourage physical activity. Drug treatment is reserved for patients with severe obesity, who have associated comorbidities and who do not respond to changes in lifestyle.(AU)

Trigliceridos/colesterol HDL: utilidad en la deteccion de sujetos obesos con riesgo para diabetes mellitus tipo 2 y enfermedad cardiovascular / Triglycerides/HDL cholesterol: utility for the detection of obese subjects with risk for diabetes mellitus type 2 and cardiovascular diseases / Triglicerideos/colesterol HDL: utilidade na deteccao de sujeitos obesos com risco para a diabetes mellitus tipo 2 e doenca cardiovascular

En la Republica Argentina, la prevalencia de obesidad se ha incrementado considerablemente y la de diabetes mellitus tipo 2 (DMT2) alcanza 12,7%. La obesidad presenta heterogeneidad y el aumento de la grasa abdominal puede incluir hipertrigliceridemia, hiperglucemia, disminucion de C-HDL, aumentos de apolipoproteina B (Apo B), aumento de lipoproteinas LDL pequenas y densas, hiperinsulinemia, insulino-resistencia (IR), estado inflamatorio cronico, estado protrombotico y otras alteraciones metabolicas, que se han reunido en el llamado sindrome metabolico con prevalencia del 20 al 40%. La resistencia a la insulina (IR) esta presente en 10 al 25% de la poblacion y se asocia con esas alteraciones. La determinacion de IR es compleja, necesita de internacion en clinicas y debe ser realizada por especialistas. En el laboratorio se puede estimar a traves del dosaje de insulina, pero no esta estandarizado, por lo que es necesario disponer de tecnicas sencillas y accesibles. La relacion trigliceridos (TG)/colesterol HDL (C-HDL) puede ser una opcion utilizando como valores de corte TG/C-HDL ≥2,5 en mujeres y ≥3,5 en varones. Se asocia significativamente con IR y enfermedad cardiovascular (ECV), tiene buena especificidad aunque bajo poder discriminador por lo cual cuando esta presente y existe riesgo de DMT2 o ECV deberia complementarse con el calculo del colesterol-no-HDL o Apo B y el colesterol remanente. Teniendo en cuenta la pandemia de obesidad y DMT2 y la elevada frecuencia de ECV, la relacion TG/C-HDL podria ser un marcador que deberia ser informado por el laboratorio bioquimico-clinico.

In Argentina, the prevalence of obesity has increased considerably and type 2 diabetes mellitus (DMT2) reaches 12.7%. Obesity presents heterogeneity and the increase in abdominal fat may include hypertriglyceridemia, hyperglycemia, decrease in HDL-C, increases in apolipoprotein B (Apo B), increase in small and dense LDL lipoproteins, hyperinsulinemia, insulin resistance (IR), chronic inflammatory state, prothrombotic state and other metabolic alterations, which have been included in the so-called metabolic syndrome with 20 to 40% prevalence. Insulin resistance is present in 10 to 25% of the population and is associated with these alterations. The determination of IR is complex; it needs hospitalization and must be performed by specialists. In the laboratory, it can be estimated through insulin dosing, but it is not standardized, so it is necessary to have simple and accessible techniques. The triglycerides (TG)/HDL cholesterol (HDL-C) ratio can be an option using TG/C-HDL cutoff values ≥2.5 in women and ≥3.5 in men. It is significantly associated with IR and CVD and has good specificity but low discriminating power. So when it is present and there is a risk of T2DM or cardiovascular disease, CVD should be complemented with the calculation of non-HDL cholesterol or Apo B and the remaining cholesterol. Considering the pandemic of obesity and DMT2 and the high frequency of CVD, the TG/C-HDL ratio marker should be reported by the biochemical-clinical laboratory.

Na Republica Argentina, a prevalencia de obesidade aumentou em forma consideravel e a de diabetes mellitus tipo 2 (DMT2) atinge 12,7%. A obesidade apresenta heterogeneidade e o aumento da gordura abdominal pode incluir hipertrigliceridemia, hiperglicemia, diminuicao do HDL-C, aumentos da apolipoproteina B (Apo B), aumento das lipoproteinas LDL pequenas e densas, hiperinsulinemia, resistencia a insulina, estado inflamatorio cronico, estado pro-trombotico e outras alteracoes metabolicas, que se encontraram na chamada sindrome metabolica, com prevalencia de 20 a 40%. A resistencia a insulina (RI) esta presente em 10 a 25% da populacao e esta associada a essas alteracoes. A determinacao da RI e complexa, precisa da hospitalizacao em clinicas e deve ser realizada por especialistas. No laboratorio, isso pode ser estimado atraves da dosagem de insulina, mas nao e padronizado, portanto e necessario ter tecnicas simples e acessiveis. A relacao triglicerideos (TG)/colesterol HDL (C-HDL) pode ser uma opcao usando como valores de corte TG/C-HDL ≥2,5 em mulheres e ≥3,5 em homens. Esta significativamente associado a RI e a doenca cardiovascular (DCV), possui boa especificidade, embora apresente baixo poder discriminador; portanto, quando esta presente e ha risco de DMT2 ou DCV, deveria ser complementado com o calculo do colesterol nao-HDL ou Apo B e o restante colesterol. Considerando a pandemia de obesidade e DMT2 e a alta frequencia de DCV, a relacao TG/C-HDL poderia ser um marcador que deveria ser relatado pelo laboratorio bioquimico-clinico.

Insulin dysregulation in horses with induced obesity / Desregulação da insulina em equinos com obesidade induzida

Insulin deregulation (ID) is a central player in the pathophysiology of equine metabolic syndrome (EMS), which is associated with generalized and/or regional obesity. The objective of this experiment was to characterize the alterations in the hormonal profile in horses exposed to a hypercaloric diet. A total of nine Mangalarga Marchador adult horses with initial body condition score (BCS) of 2.9±1/9 (mean±SD) were submitted to a high calorie grain-rich diet for 5 months. The data was collected before the start of the experiment and every 15 days until the end of the experiment and glucose and insulin concentrations were measured in the plasma. Proxies G:I, RISQI, HOMA-IR and MIRG were calculated. The low-dose oral glucose tolerance test (OGTT) was performed and the total area under the glucose (GTA) and insulin (ITA) curves at three different timepoints (before inducing obesity, after 90 days and after 150 days) was used. Analysis of variance of the results was performed considering the time effects and the means were compared with repeated measures by the Tukey's test (P≤0.05). The ID was observed during the first 90 days of the experiment and was characterized as a decompensated ID, showing an increase of basal glucose and insulin plasma levels, changes in all proxies and a significant increase in GTA (P<0.001) and ITA (P<0.05). However, a clear compensation of the ID was evident after 150 days of experiment, which was supported by data from the insulin secretory response of ß cells of the pancreas that showed an increase in insulin plasma levels, after fasting or exposure to gastric glucose, with a concomitant decrease in fasting glucose and fructosamine levels, and a decrease of GTA and marked increase of ITA (P<0.0001) in the dynamic test. These findings confirm the occurrence of hyperinsulinemia associated with insulin deregulation in Mangalarga Marchador horses exposed to hypercaloric diets.(AU)

A desregulação insulínica (DI) é o ponto central dos mecanismos fisiopatológicos da síndrome metabólica equina (SME), que é associada à obesidade generalizada e/ou regional. O objetivo deste experimento foi caracterizar as alterações no perfil hormonal em equinos submetidos à dieta hipercalórica. Foram utilizados nove equinos Mangalarga Marchador adultos com escore corporal (EC) médio (±DP) inicial de 2,9±1 (escala de 1-9) submetidos à dieta hipercalórica atingindo um EC de 8,3±1 após cinco meses. Os dados foram coletados antes do início do experimento e com o intervalo de 15 dias até o final do experimento, os valores plasmáticos foram obtidos para mensuração das concentrações de glicose e insulina. Foram calculados os proxies G:I, RISQI, HOMA-IR e o MIRG. Foi realizado o teste de baixa dose de glicose oral (TBDGO) utilizando a área total sob a curva de glicose (ATG) e insulina (ATI) em três momentos, antes da indução a obesidade, após 90 e 150 dias. Os resultados foram submetidos à análise de variância considerando-se os efeitos de tempo e as médias comparadas com medidas repetidas pelo teste de Tukey, com o valor P≤0,05. A DI foi observada nos primeiros 90 dias de experimento, se caracterizando como um quadro de DI descompensada, apresentando um aumento dos níveis plasmáticos basais de glicose e insulina, pelas alterações em todos os proxies e com um aumento significativo da ATG (P<0,001) e ATI (P<0,05). Contudo, ficou evidente uma compensação do quadro de DI após 150 dias de experimento, sendo demonstrado pelos dados da resposta secretória insulínica das células ß do pâncreas, que se manifestaram pelo aumento dos níveis plasmáticos de insulina pós-jejum ou exposição à glicose gástrica com concomitante redução nos níveis de glicose e frutosamina pós-jejum e pela redução da ATG e pela marcada elevação de ATI (P<0,0001) no teste dinâmico. Tais achados comprovam a ocorrência de hiperinsulinemia associada à desregulação insulínica em equinos Mangalarga Marchador expostos a dietas à dieta hipercalórica.(AU)

Soluble insulin receptor and metabolic syndrome

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e., metabolic syndrome. Electrophoresis of the rats’ plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

Resistencia a la insulina en mujeres con síndrome de ovario poliquístico / Insulin resistance in women with polycystic ovary syndrome

RESUMEN Introducción: La resistencia a la insulina es frecuente en el síndrome de ovario poliquístico, con diferencias entre fenotipos y discrepancias sobre cómo medirla. Objetivo: Identificar trastornos de la sensibilidad y resistencia a la insulina en mujeres con síndrome de ovario poliquístico, y determinar si es mayor en el fenotipo clásico. Métodos: Incluyó 152 mujeres: 45 sin síndrome de ovario poliquístico (Grupo I); 46 con síndrome de ovario poliquístico clínico (Grupo II); 61 con síndrome de ovario poliquístico clásico (Grupo III). Se realizó prueba de tolerancia a la glucosa oral, se calcularon índices de sensibilidad o resistencia a la insulina en ayunas (HOMA-IR, I0/G0, FIRI, ISI, Belfiore, Bennet, Quicki, Raynaud) y en la prueba de tolerancia a la glucosa oral (Belfiore2, Ribel, Ins2glu2, ATI, IITotal, DATI/DATG, Matsuda, BetaHOMA). Se emplearon las pruebas de Kruskal-Wallis, Mann-Whitney y Chi cuadrado. Resultados: Las mujeres con síndrome de ovario poliquístico tenían más obesidad global y central (p / 0,05), más nivel de glucemia a los 30, 120 y 180 minutos de la prueba de tolerancia a la glucosa oral (p / 0,05) y de insulinemia a los 30, 60 y 120 (p / 0,0001), lo que fue mayor en el grupo III. Se diagnosticó intolerancia en ayunas en una mujer de cada grupo y tolerancia alterada en una del II y III. No hubo diferencias significativas entre grupos para los índices de sensibilidad o resistencia a la insulina en ayunas; ni del HOMA entre mujeres normopeso vs. sobrepeso-obesidad (p / 0,05). La mediana de los índices de la prueba de tolerancia a la glucosa oral fue menor para los de sensibilidad (Belfiore2, Ribel) y mayor para los de resistencia a la insulina (Ins2glu2, ATI, IITotal) en el Grupo III. El DATI/DATG, Matsuda y BetaHOMA no tuvieron diferencias significativas. Conclusiones: Las mujeres con síndrome de ovario poliquístico tienen mayor respuesta glucémica, resistencia a la insulina e hiperinsulinismo postsobrecarga de glucosa que las mujeres con función ovárica normal, más manifiesta en el fenotipo clásico. Los índices de ayuno son menos sensibles, independientemente del peso corporal. Tienen mayor utilidad: insulinemia a los 60 minutos de la prueba de tolerancia a la glucosa oral, Belfiore2, ATI e IITotal(AU)

ABSTRACT Introduction: Insulin resistance is common in polycystic ovary syndrome, with differences between phenotypes and discrepancies on how to measure it. Objective: To identify disorders of insulin sensitivity and resistance in women with polycystic ovarian syndrome and determine if the latter is greater in the classic phenotype. Methods: The study included 152 women. 45 of them had no polycystic ovary syndrome (Group I), 46 had clinical polycystic ovary syndrome (Group II) and 61 had classic polycystic ovary syndrome (Group III). Oral glucose tolerance test was performed, fasting insulin sensitivity or resistance indices (HOMA-IR, I0 / G0, FIRI, ISI, Belfiore, Bennet, Quicki, Raynaud) were calculated and the tolerance test to oral glucose (Belfiore2, Ribel, Ins2glu2, ATI, IITotal, DATI / DATG, Matsuda, BetaHOMA) was also assessed. Kruskal-Wallis, Mann-Whitney and Chi square tests were used. Results: Women with polycystic ovarian syndrome had more global and central obesity (p /0.05), more blood glucose level at 30, 120 and 180 minutes of the oral glucose tolerance test (p /0.05 ) and insulinemia at 30, 60 and 120 (p /0.0001), which was higher in group III. Fasting intolerance was diagnosed in one woman in each group and altered tolerance in one of group II and group III, respectively. There were no significant differences between groups for fasting insulin sensitivity or resistance indices, nor for HOMA among normal weight women vs. overweight-obesity (p / 0.05). The median indexes of the oral glucose tolerance test were lower for those of sensitivity (Belfiore2, Ribel) and higher for those of insulin resistance (Ins2glu2, ATI, IITotal) in Group III. The DATI / DATG, Matsuda and BetaHOMA had no significant differences. Conclusions: Women with polycystic ovarian syndrome have higher glycemic response, insulin resistance and post-overload glucose hyperinsulinism than women with normal ovarian function, which is more evident in the classical phenotype. Fasting rates are less sensitive, regardless of body weight. Tests such as insulinemia 60 minutes after the oral glucose tolerance, Belfiore 2, ATI and IITotal are most useful(AU)

Hipoglucemia por hiperinsulinismo endógeno / Endogenous hyperinsulinism hypoglycemia

RESUMEN La hipoglucemia por hiperinsulinismo endógeno constituye un reto terapéutico. Se describen las características clínicas, bioquímicas e imagenológicas de pacientes con diagnóstico de hiperinsulinismo endógeno atendidos en el Instituto Nacional de Endocrinología en el periodo 2004-2018(AU)

ABSTRACT Hypoglycemia due to endogenous hyperinsulinism constitutes a therapeutic challenge. The clinical, biochemical and imaging characteristics of patients diagnosed with endogenous hyperinsulinism treated at the National Endocrinology Institute from 2004 to 2018 are described(AU)

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.

Síndrome de Ovarios Poliquísticos / Polycystic ovary syndrome

Resumen El síndrome de ovarios poliquísticos (SOPQ) es la disfunción endocrino- metabólica más frecuente en mujeres de edad reproductiva. El diagnostico de esta patología se basa en la presencia de anovulación, hiperandrogenismo y ovarios poliquísticos. La etiología del SOPQ es compleja y multifactorial; por lo cual el tratamiento se basa en tratar las manifestaciones clínicas y la inducción de la ovulación en el momento que se desee la concepción.

Abstract Polycystic ovary syndrome is the most common endocrinologic and metabolic disfunction in reproductive- aged women. The diagnosis of this pathology is based on the presence of ovulatory dysfunction, hyperandrogenism and polycystic ovaries. Its ethiology is complex and with multiple factors, therefore its treatment is based on fixing the clinical manifestations of the syndrome and in the case of women who would like to conceive, in inducing ovulation.

Forma activa de la vitamina D en pacientes pediátricos con sobrepeso y obesidad en el noroeste de México / Active form of vitamin D in overweight and obese pediatric patients in northwest Mexico

Resumen: Introducción: Los niveles bajos de vitamina D se han asociado con una gama de condiciones clínicas como obesidad, resistencia a la insulina y diabetes mellitus. Existen pocos estudios donde se hayan realizado mediciones de la forma activa de la vitamina D (1,25 (OH)2 vitamina D) en niños con obesidad. Sin embargo, los datos publicados no son concluyentes. El objetivo de este estudio fue determinar los niveles de la forma activa de la vitamina D en niños con obesidad y sobrepeso y determinar la asociación entre los niveles bajos de esta vitamina, la obesidad y las alteraciones del metabolismo de la glucosa. Métodos: Estudio transversal analítico en niños de 6 a 12 años de edad con exceso de adiposidad determinado por el índice cintura-estatura y el índice Z de masa corporal. Se midieron niveles de glucosa, insulina, perfil de lípidos completo, modelo homeostático para evaluar la resistencia a la insulina y la forma activa de la vitamina D. Se consideraron como niveles bajos de vitamina D aquellos menores a 30 pg/ml. Resultados: La prevalencia de niveles bajos de la forma activa de la vitamina D fue del 36%. La asociación entre niveles bajos de la forma activa de la vitamina D y niveles altos de insulina resultó estadísticamente significativa. No se encontró asociación significativa entre los niveles de la vitamina y las medidas de adiposidad. Conclusiones: Se encontraron niveles bajos de la forma activa de la vitamina D en el 36% de la población estudiada, y se demostró su asociación con la resistencia a insulina e hiperinsulinemia.

Abstract: Background: Low levels of vitamin D have been associated with a range of clinical conditions such as obesity, insulin resistance, and diabetes mellitus, among others. There are few studies that measure the active form of vitamin D (1,25 (OH)2 vitamin D) in obese children. However, published data are inconclusive. The aim of this study was to determine the active levels of vitamin D in obese and overweight children and to find an association between low levels of vitamin D, obesity and impaired glucose metabolism. Methods: A cross-sectional, analytical study was conducted in 6 to 12-year-old children with excess adiposity determined by waist-stature index and body mass index. Levels of glucose, insulin, complete lipid profile, homeostatic model assessment and the active form of vitamin D were measured in each patient. Levels < 30 pg/ml were considered as low levels of vitamin D. Results: The prevalence of low levels of active vitamin D was 36%. A significant association between low levels of active vitamin D and high levels of insulin was found. No significant association was found between vitamin levels and adiposity measures. Conclusions: Low levels of active vitamin D were found in 36% of the population studied. A significant association with insulin resistance and hyperinsulinemia was demonstrated.

Masa pancreática: una presentación inhabitual de nesidioblastosis en el adulto / Pancreatic mass: an unusual presentation of nesidioblastosis in adults

A 41-year-old woman, multiparous of 4, with personal or familiar history of diabetes, with a history of Nissen fundoplication due to pathological gastro-oesophageal reflux, is refer to an endocrinologjst during her post-operatiye follow up, 4 months after her surgery for a 14 kg weight loss in 10 months and symtomatic hypoglycemia to repetition. A positive prolonged fasting test for hypoglycemia was performed. In addition, abdominal computed axial tomography was performed, which resulted normal and endosonography, showing a lesion on the head of the pancreas. Octreoscan positive for pancreatic head focal lesion with positive somatostatin receptors compatible with insulinoma. Whipple surgery was performed where surgeon palpated pancreatic tumor, biopsy showed tissue compatible with diffuse nesidioblastosis. In the postoperative period, the patient decreased frequency and intensity of hypoglycemic episodes compared to their previous stage. Control prolonged fasting test and Octreoscan were within normal ranges. However, 4 months after surgery, the patient presented hypoglycemia of lower intensity and frequency than before surgery. Currently he remains in control with nutritionist and endocrinologist, mainly adjusting diet and with good control glycemias.

Equine metabolic syndrome in Colombian creole horse: case report / Síndrome metabólica equina em cavalo crioulo Colombiano: relato de caso

The equine metabolic syndrome is a condition that can be recognized because of obesity, insulin resistance and laminitis. Genetic factors could play a role in the occurrence of this syndrome. Certain breeds such as ponies (including the South American creole horses) have a lower sensibility to insulin and a higher prevalence of hyperinsulinemia. The environment and management conditions, such as overfeeding and lack of exercise are factors that bring a propensity for obesity. The adipose tissue works as an endocrine organ producing hormones (adipokines or adipocytokines) that affect the horse´s metabolism. The objective of this report is to describe the first case report of a Colombian creole mare with a metabolic syndrome, diagnosed by means of the combined test of glucose-insulin and clinical signs. Early diagnosis of this entity and an adequate treatment are useful for improving the life and the zootechnical conditions of the patient.(AU)

A síndrome metabólica equina é uma alteração reconhecida por apresentar obesidade, resistência à insulina e laminite. Fatores genéticos poderiam ser relevantes na ocorrência dessa síndrome, em que certas raças consideradas pôneis (incluídas as raças crioulas de cavalos sul-americanos) têm mais baixa sensibilidade à insulina e mais alta prevalência de apresentar hiperinsulinemia. As condições ambientais e de manejo, como superalimentação e falta de exercício, são fatores predisponentes para o desenvolvimento da obesidade. O tecido adiposo cumpre atividades como um órgão endócrino produtor de hormônios (adipocinas ou adipocitocinas) que afetam o metabolismo do cavalo. O objetivo deste relatório é descrever o primeiro registro de caso de uma égua de raça Cavalo Crioulo Colombiano (CCC) com síndrome metabólica, diagnosticada pela prova combinada de glicose-insulina e por quadro clínico. O diagnóstico precoce desta entidade e seu tratamento adequado permitem melhorar as condições de vida e zootécnicas do paciente que dela padece.(AU)

Nesidioblastosis del adulto tras derivación gástrica / Nesidioblastosis in the adult following gastric bypass

La hipoglucemia por hiperinsulinismo endógeno ha sido descrita como una complicación de la cirugía bariátrica. Se presenta el caso de un hombre de 34 años con tríada de Whipple que se manifestó ocho años después de someterse a derivación (bypass) gástrica. La hipoglucemia se asociaba con niveles elevados de insulina y péptido C, pero la localización del hiperinsulinismo endógeno solo se pudo precisar mediante cateterismo de arterias pancreáticas con estimulación intraarterial selectiva con calcio. Se decidió practicar una pancreatectomía subtotal laparoscópica, después de la cual el paciente presentó una excelente evolución posoperatoria y mejoró significativamente su sintomatología. Mediante la evaluación histopatológica e inmunohistoquímica, se confirmó una nesidioblastosis del adulto. Es importante reconocer esta enfermedad como una complicación de la cirugía bariátrica, más aún cuando estos procedimientos son tan frecuentes en la actualidad debido a la epidemia de obesidad. Los síntomas se pueden confundir con los de un síndrome de evacuación gástrica rápida (dumping), el cual no tiene repercusiones tan graves sobre la salud del paciente, como sí la tiene la nesidioblastosis

Hypoglycemia due to endogenous hyperinsulinism has been described as a complication of bariatric surgery. We present the case of a 34-year-old man who developed a Whipple's triad eight years after undergoing gastric bypass. Hypoglycemia was associated with high serum levels of insulin and C peptide; anatomic localization of endogenous hyperinsulinism was finally demonstrated with a selective intra-arterial calcium-stimulation test. Patient was offered a laparoscopic subtotal pancreatectomy, which resulted in an excellent postoperative course and significant symptoms resolution. Pathology report and inmunohistochemical analysis confirmed the diagnosis of adult nesidioblastosis. We believe it is important to recognize this condition as a complication of bariatric surgery, a procedure performed more frequently nowadays due to the obesity epidemic. Symptoms might be confused with those of dumping syndrome which does not have severe consequences in the patient´s health as nesidioblastosis does

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.

Insulinoma pancreático gigante / Giant pancreatic insulinoma

Los insulinomas son los tumores neuroendocrinos pancreáticos más frecuentes y típicamente son benignos y pequeños. Los insulinomas gigantes de páncreas son tumores raros. Reportamos el caso de un paciente varón de 67 años, quien presentaba síntomas y signos de hipoglicemia. Subsecuentes estudios de laboratorio y radiológicos establecieron el diagnóstico de un insulinomade 13,5 cm. Fue sometido a pancreaticoduodenectomía. A pesar del tamaño, en la evaluación patológica no se identificó invasión localni metástasis. Además de la descripción de la presentación clínica y los hallazgos operatorios, se realiza una revisión de las opcionespara la localización y manejo de los insulinomas.

Insulinomas are the most common pancreatic neuroendocrine tumors and are typically small and benign. Giant pancreatic insulinomasare rare pancreatic tumors. We report a 67 year old man who presented with signs and symptoms of hypoglycemia. Subsequentlaboratory and radiologic studies established the diagnosis of a 13.5 cm insulinoma. The patient underwent a pancreatoduodenectomy.Despite the size, neither local invasion nor metastatic disease was identified on pathological evaluation. In addition to describing theclinical presentation and operative findings, localization and management options of insulinomas are reviewed.

PROPOSAL OF A REVISIONAL SURGERY TO TREAT NON-INSULINOMA HYPERINSULINEMIC HYPOGLICEMIA POSTGASTRIC BYPASS / PROPOSTA DE CIRURGIA REVISIONAL PARA TRATAMENTO DE HIPOGLICEMIA HIPERINSULINEMICA NÃO INSULINOMA APÓS BYPASS GÁSTRICO

Background : Hyperinsulinemic hypoglicemia with severe neuroglycopenic symptoms has been identified as a late and rare complication in patients submitted to Roux-en-Y gastric bypass. However, the potential gravity of its manifestations requires effective treatment of this condition. The absence of treatment makes it necessary to develop more effective clinical or surgical methods. Aim : To present one surgical option to revisional surgery in the treatment of hyperinsulinemic hypoglicemia Methods : The procedure consists in reconstituting alimentary transit through the duodenum and proximal jejunum, while keeping the restrictive part of the gastric bypass. As an additional strategy to maintain weight loss, is realized gastric fundus resection, aiming to suppress ghrelin production more effectively. Results : It was used in three patients with successful results in one year of follow-up. Conclusion : The procedure to reconstruct the food transit through the duodenum and proximal jejunum, keeping the restrictive component of gastric bypass in the treatment of hyperinsulinemic hypoglycemia showed good initial results and validated its application in other cases with this indication.

Racional : Hipoglicemia hiperinsulinêmica com sintomas neuroglicopênicos severos tem sido identificada como complicação tardia e rara em pacientes submetidos à gastroplastia com bypass em Y-de-Roux. Porém, a gravidade potencial de suas manifestações exige tratamento definitivo desta condição. A falta de tratamento efetivo gera a necessidade de desenvolver métodos clínicos ou cirúrgicos mais eficazes. Objetivo: Apresentar proposta de operação revisional para o tratamento da síndrome de hipoglicemia hiperinsulinêmica. Métodos : O procedimento consiste em reconstituir o trânsito alimentar pelo duodeno e jejuno proximal, mantendo o componente restritivo do by-pass gástrico. Como estratégia adicional de manutenção ponderal, é realizada ressecção do fundo gástrico, visando intensificar a supressão da grelina. Resultado: O procedimento foi realizado em três pacientes com bom resultado em seguimento de um ano. Conclusão : O procedimento de reconstituir o trânsito alimentar pelo duodeno e jejuno proximal, mantendo o componente restritivo do by-pass gástrico no tratamento da hipoglicemia hiperinsulinêmica apresentou bons resultados iniciais podendo validar sua indicação para outros casos.

Both hepatic lipogenesis and beta-oxidation are altered in offspring of mothers fed a high-fat diet in the first two generations (F1 and F2) / La lipogénesis hepática y la beta-oxidación están alteradas en las crías de madres alimentadas con una dieta alta en grasas en las dos primeras generaciones (F1 y F2)

The high fat (HF) fed mothers may program susceptibility in offspring to chronic diseases and affect subsequent generations. The present study evaluated the liver structure in adulthood, focusing on the F1 and F2 generations. Females C57BL/6 (F0) were fed standard chow (SC) or HF diet (8 weeks) prior to mating and during the gestation and lactation to provide the F1 generation (SC-F1 and HF-F1). All other mothers and offspring fed SC. At 3 months old, F1 females were mated to produce the F2 generation (SC-F2 and HF-F2). The liver was kept in several fragments and prepared for histological analysis or frozen for biochemical and molecular analyzes. The F1 and F2 offspring were studied at 3 months old. HF-F1 had higher body mass (BM) compared to SC-F1 (P= 0.001), but not HF-F2 compared to SC-F2. HF-F1 had glucose intolerance when compared to SC-F1, but not HF-F2 compared to SC-F2. HF-F1 (P= 0.009) and HF-F2 (P= 0.03) showed hyperinsulinemia compared to their counterparts. Both groups HF-F1 and HF-F2 showed more steatosis than the SC counterparts (F1 and F2, P<0.0001). HF-F1 showed increased expression of PPAR-gamma and SREBP1-c compared to SC-F1 (P= 0.01). HF-F2 showed increased PPAR-gamma expression compared to SC-F2 (P= 0.04). In conclusion, HF-fed mother impairs both lipogenesis and beta-oxidation pathways in F1 through upregulation of PPAR-gamma and downregulation of PPAR-alpha. In F2, the only lipogenesis is enhanced, but it causes a disrupted PPAR balance, favoring the hepatic lipid accumulation and impaired metabolism in these animals that were not directly exposed to the maternal HF intake.

Los madres alimentadas con dieta rica en grasas (HF) pueden programar una susceptibilidad al desarrollo de enfermedades crónicas en su descendencia y de este modo afectar a las generaciones posteriores. El presente estudio evaluó la estructura del hígado en la edad adulta, centrándose en las generaciones F1 y F2. Las hembras C57BL/6 (F0) fueron alimentadas con dieta estándar (CS) o dieta HF (8 semanas) antes del apareamiento y durante la gestación y lactancia para producir la generación F1 (CS-F1 y HF-F1). Todas las demás madres y crías fueron alimentadas con CS. A los 3 meses de edad, las hembras F1 fueron apareadas para producir la generación F2 (CS-F2 y HF-F2). El hígado se conservó en varios fragmentos y se preparó, por un lado, para el análisis histológico, y por otro, se lo congeló para realizar análisis bioquímicos y moleculares. La descendencia F1 y F2 se estudió a los 3 meses de edad. HF-F1 tuvo una mayor masa corporal (BM) en comparación con CS-F1 (P= 0,001), pero no el grupo HF-F2 en comparación con CS-F2. HF-F1 tenía intolerancia a la glucosa en comparación con CS-F1, pero no el grupo HF-F2 en comparación con CS-F2. HF-F1 (P= 0,009) y HF-F2 (P= 0,03) mostraron hiperinsulinemia en comparación con sus homólogos. Ambos grupos HF-F1 y HF-F2 mostraron más esteatosis que las contrapartes CS (F1 y F2, P <0,0001). HF-F1 mostró una mayor expresión de PPAR-gamma y SREBP1-c en comparación con el grupo CS-F1 (P= 0,01). HF-F2 mostró aumento de la expresión de PPAR-gamma en comparación con CS-F2 (P= 0,04). En conclusión, la madre alimentada con HF presenta ambas vías afectadas, de lipogénesis y de la beta-oxidación, en la F1 a través de la regulación positiva de PPAR-gamma y con regulación a la baja de los PPAR-alfa. En F2, solo ha mejorado la vía de lipogénesis, pero causa un desbalance de PPAR, lo que favorece la acumulación de lípidos hepáticos y la alteración del metabolismo en estos animales que no estaban directamente expuestos a la ingesta materna de HF.

Hyperinsulinemia and hyperglycemia: risk factors for recurrence of benign paroxysmal positional vertigo / Hiperinsulinismo e hiperglicemia: fatores de risco para recorrência de vertigem postural paroxística benigna

INTRODUCTION: Changes in carbohydrate metabolism may lead to recurrence of benign paroxysmal positional vertigo.OBJECTIVE: To evaluate the influence of the disturbance of carbohydrate metabolism in the recurrence of idiopathic BPPV.METHODS: A longitudinal prospective study of a cohort, with 41 months follow-up. We analyzed the results of 72 glucose-insulin curves in patients with recurrence of BPPV. The curves were classified into intolerance, hyperinsulinemia, hyperglycemia and normal.RESULTS: The RR for hyperinsulinism was 4.66 and p = 0.0015. Existing hyperglycemia showed an RR = 2.47, with p = 0.0123. Glucose intolerance had a RR of 0.63, with p = 0.096. When the examination was within normal limits, the result was RR = 0.2225 and p = 0.030.DISCUSSION: Metabolic changes can cause dizziness and vertigo and are very common in people who have cochleovestibular disorders. However, few studies discuss the relationship between idiopathic BPPV and alterations in carbohydrate metabolism. In the present study, we found that both hyperglycemia and hyperinsulinemia are risk factors for the recurrence of BPPV, whereas a normal test was considered a protective factor; all these were statistically significant. Glucose intolerance that was already present was not statistically significant in the group evaluated.CONCLUSION: Hyperinsulinemia and hyperglycemia are risk factors for the recurrence of idiopathic BPPV and a normal exam is considered a protective factor.

INTRODUÇÃO: As alterações do metabolismo do carboidrato podem levar a recorrência de vertigem posicional paroxística benigna.OBJETIVO: Avaliar a influência dos distúrbios do carboidrato na recorrência da VPPB idiopática.MÉTODO: Estudo longitudinal, do tipo coorte, prospectivo, com 41 meses de acompanhamento. Analisaram-se 72 resultados de curvas glicoinsulinêmicas em pacientes portadores de recorrência de VPPB. As curvas foram classificadas em intolerância, hiperinsulinemia, hiperglicemia e normal.RESULTADOS: O hiperinsulinismo teve RR = 4,66 e p = 0,0015. A hiperglicemia apresentou um RR = 2,47 e p = 0,0123. Na intolerância a glicose o RR = 0,63 e p = 0,096. No exame normal, o RR = 0,2225 e p = 0,030.DISCUSSÃO: As alterações metabólicas podem causar tontura e vertigem e são muito frequentes na população que apresenta distúrbios cocleovestibulares. Contudo, poucos trabalhos falam sobre a relação entre a VPPB idiopática e as alterações nos carboidratos. No presente estudo, verificou-se que tanto a hiperglicemia, quanto o hiperinsulinismo são fatores de risco para recorrência de VPPB, ao passo que o exame normal foi considerado fator protetor, todos estes estatisticamente significantes. Já a intolerância à glicose não teve significância estatística no grupo avaliado.CONCLUSÃO: O hiperinsulinismo e a hiperglicemia se comportam como fatores de risco para a recorrência de VPPB idiopática, assim como o exame normal como um fator protetor.

Hierro excesivo y cardiopatía coronaria énfasis en la generación de diabetes y muerte súbita / Excessive iron and coronary cardiopathy emphasis in the generation of diabetes and sudden death

El Hierro es esencial para la vida, pero su exceso libre o acumulado es un tóxico celular, puesto que es el metal que menos se elimina en el humano. Es un potente creador de radicales libres que genera/incrementa significativamente el estrés oxidativo. El hierro influencia el metabolismo de la glucosa, inclusive en ausencia de sobrecargas elevadas; incrementa el daño cardiovascular pre- existente, y su reducción alivia la patología cardiaca coronaria y reducir o prevenir sus complicaciones. Ciertamente, elevados niveles de hierro catalítico y/o acumulado como ferritina aumenta el riesgo para el desarrollo de aterosclerosis coronaria. El hierro libre cataliza la peroxidación lipídica; al igual que las mayores reservas corporales de hierro aceleraría la disfunción endotelial en la patología isquémica aguda: el exceso del hierro genera una injuria vascular oxidativa /inflamatoria /protrombótica vascular e insulinoresistencia. En la población general, las reservas corporales férricas se asocian estrechamente con el desarrollo de intolerancia glucídica, diabetes tipo 2 y gestacional; y aumenta silenciosamente las complicaciones del sujeto dislipidémico, hipertenso, y diabético. Se ha demostrado que la donación /extracción de sangre por flebotomía reduce significativamente la incidencia y gravedad de los eventos coronaríos: la isquemia por reperfusión, y procedimientos como la angioplastia coronaria transluminal transluminal percutánea y el bypass coronario (Holsworth, 2013). La donación frecuente de sangre conduce a una reducción de las reservas de hierro y disminuye el exceso de insulina (basal y post-prandíal), mejorando la sensibilidad insulínica encontroles sanos; y los parámetros hemodinámicos - metabólicos en sujetos hipertensos y diabéticos...

Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Iron overload has been suggested to increase the cardiovascular risk in the general population. Iron influences glucose metabolism, even in the absence of significant iron overload, and its reduction may alleviate coronary heart disease and reduced or prevent their complications. In fact, high stored or free iron levels (measured by serum ferritin or catalytic iron concentrations) elevate risk for development of coronary atherosclerosis. Increased body iron stores may accelerate endothelial dysfunction in acute ischemic syndromes. Then, excess body iron originates oxidative injury that is associated with systemic and vascular inflammation, phrothrombotic conditions and insulin resistance (Williams, 2002) In the general population, body iron stores are positively associated with the development of glucose intolerance, type 2 diabetes and gestational diabetes. Further, it has been demonstrated that blood donation significant drops in the incidence of cardiovascular events, as well as in procedures such as percutaneous transluminal coronary angioplasty and coronary artery bypass grafting (Holsworth, 2013). Accordingly, frequent blood donations decreased iron stores in healthy volunteers, improving insulin sensitivity and hemodynamic parameters. This sample therapy constitutes a protective factor for the development of type 2 diabetes, and the cardiac disorders insulin-resistance associated...