Estudio comparativo de la terapia de metformina sola y metformina combinada con terapia de tintura de notholaena nivea en pacientes con diabetes tipo 2 / Comparative study of metformin therapy alone and metformin combined with notholaena nivea tincture therapy in patients with type 2 diabetes

La diabetes tipo 2 es un trastorno metabólico progresivo complejo, que representa una amenaza significativa para la salud humana y representa más del 91% de todos los casos de diabetes. Objetivo: evaluar el efecto de la adición de tintura de Notholaena nivea al tratamiento con metformina en pacientes con tolerancia alterada a la glucosa (IGT) y diabetes de tipo 2 (DMT2). Materiales y Método: Ensayo clínico unicentral, aleatorizado, simple ciego, controlado con placebo. Todos los participantes con diagnóstico de IGT y DMT2 que tomaban metformina fueron asignados aleatoriamente a recibir kits con tintura de Notholaena nivea autentica (40 pacientes) o placebo (58 pacientes), fijando 6 gotas diarias, 30 minutos antes del desayuno y almuerzo durante 26 semanas, se hicieron 3 controles (0, 13 y 26 semanas) midiendo glucosa plasmática en ayunas (FPG), nivel de hemoglobina glucosilada (HbA1C) y perfil lipídico. Resultados: del grupo de tratamiento (tintura de Notholaena nivea más metformina) fueron significativamente eficientes a las 13 semanas de iniciado el ensayo, manteniendo la directriz de reducción de glucosa plasmática (FPG), al iniciar el estudio el grupo control y tratamiento obtuvieron niveles de FPG similares con valores de .57±1.7 y 7.84±1.9 mmol/l respectivamente (p>0.05), a las 13 semanas se redujo a 7.21±1.mmol/l para el grupo control y 6.49±2.33 mmol/l para el grupo tratamiento (p<0.01), mientras que a la semana 26 el grupo control reporto 7.09±1.41 mmol/l en tanto el grupo tratamiento obtuvo 5.98±0.71 mmol/l (p<0.01). Hubo reducción de los niveles de HbA1C dentro de los grupos, pero no se evidenciaron diferencias por efecto del tratamiento. En el perfil lipídico el tratamiento de Metformina sola evidencio una mejor respuesta con la reducción de colesterol total y aumento de lipoproteínas de alta densidad (HDL) pero aumento la concentración de triglicéridos, mientras que el tratamiento con tintura de Notholaena nivea mantuvo los perfiles lipídicos al igual que en un inicio (p>0.05). Conclusiones: el tratamiento combinado de metformina más tintura de Notholaena nivea reduce acelerada y eficazmente las concentraciones de FPG en sangre de pacientes con IGT o DMT2, pero es ineficaz en el tratamiento del perfil lipídico(AU)

Type 2 diabetes is a complex progressive metabolic disorder, which represents a significant threat to human health and accounts for more than 91% of all diabetes cases. Objective: to evaluate the effect of adding Notholaena nivea tincture to metformin treatment in patients with impaired glucose tolerance (IGT) and type 2 diabetes (DMT2). Materials and Method: Unicentral, randomized, single-blind, placebo-controlled clinical trial. All participants diagnosed with IGT and T2DM who were taking metformin were randomly assigned to receive authentic Notholaena nivea tincture kits (40 patients) or placebo (58 patients), setting 6 drops daily, 30 minutes before breakfast and lunch for 26 weeks. , 3 controls were made (0, 13 and 26 weeks) measuring fasting plasma glucose (FPG), glycosylated hemoglobin level (HbA1C) and lipid profile. Results: the treatment group (Notholaena nivea tincture plus metformin) were significantly efficient at 13 weeks from the start of the trial, maintaining the plasma glucose reduction guideline (FPG), at the start of the study the control and treatment groups obtained levels of Similar FPG with values of .57±1.7 and 7.84±1.9 mmol/l respectively (p>0.05), at 13 weeks it was reduced to 7.21±1.mmol/l for the control group and 6.49±2.33 mmol/l for the treatment group (p<0.01), while at week 26 the control group reported 7.09±1.41 mmol/l while the treatment group obtained 5.98±0.71 mmol/l (p<0.01). There was a reduction in HbA1C levels within the groups, but no differences due to treatment effect were observed. In the lipid profile, the treatment with Metformin alone showed a better response with the reduction of total cholesterol and an increase in high-density lipoproteins (HDL) but increased the concentration of triglycerides, while the treatment with Notholaena nivea tincture maintained the lipid profiles at the same as at the beginning (p>0.05). Conclusions: the combined treatment of metformin plus Notholaena nivea tincture rapidly and effectively reduces FPG concentrations in the blood of patients with IGT or DMT2, but it is ineffective in the treatment of the lipid profile.Keywords: Type 2 diabetes, Notholaena nivea, FPG, Metformin, lipid(AU)

Factores de riesgo cardiovascular en familiares de primer grado de mujeres con síndrome de ovario poliquístico / Cardiovascular Risk Factors in First-Degree Relatives of Women with Polycystic Ovary Syndrome

Introducción: El síndrome de ovario poliquístico es una entidad que, más allá de las afectaciones reproductivas que lo caracterizan, constituye un factor de riesgo de enfermedad cardiovascular. Esto último, adquiere mayor relevancia debido a que ha aumentado en la mujer que padece el síndrome y también en sus familiares. Objetivo: Demostrar que los familiares de primer grado de las mujeres con el síndrome de ovario poliquístico tienen mayor frecuencia de trastornos del metabolismo hidrocarbonado, dislipidemia y resistencia a la insulina. Métodos: Se realizó un estudio descriptivo transversal con 36 familiares de primer grado de mujeres con y sin síndrome de ovario poliquístico. Se les realizó un examen físico para comprobar el peso, la talla y la tensión arterial para descartar hipertensión en el momento de la inclusión. Resultados: La media del índice HOMA-IR en el grupo de estudio fue de 3,3 y en el de control 2,4. La prueba de tolerancia a la glucosa de 2 horas diagnosticó una glucosa alterada en ayunas a 9 familiares, 5 (55,6 por ciento) del grupo de estudio y 4 (44,4 por ciento), del grupo control. Hubo 7 familiares a los que se les detectó una tolerancia a la glucosa alterada, 6 (85,7 por ciento) familiares de mujeres con el síndrome y 1 (14,3 por ciento), del grupo control. Conclusiones: Los factores de riesgo cardiovasculares clásicos estudiados son más frecuentes en los familiares de mujeres con síndrome de ovario poliquístico que en los familiares de mujeres sin dicha enfermedad(AU)

Introduction: Polycystic ovary syndrome is an entity that, beyond the reproductive affectations that characterize it, constitutes a risk factor for cardiovascular disease. This aspect acquires greater relevance because the associated entity is not only increasing among the women who suffers from the syndrome, but also among their family members. Objective: To show that first-degree relatives of women with polycystic ovary syndrome present a higher frequency of carbohydrate metabolism disorders, dyslipidemia and insulin resistance. Methods: A cross-sectional and descriptive study was carried out with 36 first-degree relatives of women with and without polycystic ovary syndrome. They underwent physical examination to check their weight, height and blood pressure, in order to rule out hypertension at the time of inclusion. Results: The mean HOMA-IR index was 3.3 in the study group and 2.4 in the control group. The two-hour glucose tolerance test permitted to diagnose impaired fasting glucose in nine relatives, five (55.6 percent) from the study group and four (44.4 percent) from the control group. Seven relatives were reported with impaired glucose tolerance, six (85.7 percent) relatives of women with the syndrome and one (14.3 percent) from the control group. Conclusions: The classic cardiovascular risk factors studied are more frequent in the relatives of women with polycystic ovary syndrome than in the relatives of women without this disease(AU)

The positive association between serum uric acid, impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus in the ELSA-Brasil study / Associação positiva entre ácido úrico sérico, glicemia em jejum alterada, tolerância glicêmica alterada e diabetes mellitus no estudo ELSA-Brasil / La asociación positiva entre ácido úrico sérico, glucosa alterada en ayunas, tolerancia a la glucosa alterada y diabetes mellitus en el estudio ELSA-Brasil

Abstract: There is a conflict in the literature regarding the association between serum uric acid (SUA) levels and glycemic status. Therefore, we evaluated the association between SUA level and glycemic status - impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus - and insulin resistance, in a large Brazilian study. This is a cross-sectional, observational study with 13,207 participants aged 35-74 years, at baseline (2008-2010) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). A multinomial regression analysis was performed to test the association between SUA and glycemic status (IFG, IGT, and newly diagnosed type 2 diabetes at the cohort baseline) after adjustments by age, sex, skin color, body mass index, physical activity, smoking, alcohol consumption, comorbidities, and medicines use. Logistic regression model was used to evaluate the association between SUA and insulin resistance by HOMA-IR. Stratified analyses by sex were performed. The mean age (standard deviation) was 51.4 (8.9) years, 55.2% of participants were women. There were 1,439 newly diagnosed diabetes. After all adjustments, higher SUA was associated with IFG, IGT, and diabetes, with odds ratio (OR) = 1.15 (95%CI: 1.06; 1.25), 1.23 (95%CI: 1.14; 1.33), and 1.37 (95%CI: 1.24; 1.51), respectively. There was association between SUA levels and insulin resistance with OR = 1.24 (95%CI: 1.13; 1.36). In analysis stratified by sex, higher SUA persisted independently associated with impaired glycemic status. Our results suggest that a higher SUA levels were significantly associated with glycemic status in a large Latin American population, mainly among women.

Resumo: Há uma controvérsia na literatura a respeito da associação entre níveis de ácido úrico sérico (AUS) e glicemia. Portanto, avaliamos a associação entre AUS e glicemia (glicemia em jejum alterada, intolerância glicêmica e diabetes mellitus), além da resistência insulínica, em uma amostra grande no Brasil. O estudo transversal observacional incluiu 13.207 participantes com idade entre 35 e 74 anos na linha de base (2008-2010) do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Foi realizada análise de regressão multivariada para testar a associação entre AUS e glicemia (glicemia em jejum alterada, intolerância glicêmica e diagnóstico novo de diabetes tipo 2 na linha de base da coorte) depois de ajustar para idade, sexo, cor, índice de massa corporal, atividade física, tabagismo, consumo de álcool, comorbidades e uso de medicação. O modelo de regressão logística foi usado para avaliar a associação entre AUS e resistência insulínica por HOMA-IR. Foram realizadas análises estratificadas por sexo. A média de idade (DP) foi 51,4 (8,9) anos, e 55,2% dos participantes eram mulheres. Houve 1.439 novos diagnósticos de diabetes. Depois de todos os ajustes, o AUS esteve associado à glicemia em jejum alterada, intolerância glicêmica e diabetes, com odds ratio (OR) = 1,15 (IC95%: 1,06; 1,25), 1,23 (IC95%: 1,14; 1,33) e 1,37 (IC95%: 1,24; 1,51), respectivamente. Houve uma associação entre níveis de AUS e resistência insulínica, com OR = 1,24 (IC95%: 1,13; 1,36). Na análise estratificada por sexo, persistiu a associação independente entre AUS elevado e glicemia. Os resultados sugerem que níveis elevados de AUS estão associados de maneira significativa com a glicemia em uma população latino-americana grande, sobretudo entre mulheres.

Resumen: Hay un conflicto en la literatura respecto a la asociación entre los niveles de ácido úrico sérico (AUS) y el estado glucémico. Por eso, evaluamos la asociación entre el nivel AUS y el estatus glucémico: glucosa alterada en ayunas (GAA), tolerancia a la glucosa alterada (TGA) y diabetes mellitus (diabetes), comparados con la resistencia a la insulina en un amplio estudio en Brasil. Se realizó un estudio transversal, observacional con 13.207 participantes, con edades comprendidas entre los 35-74 años, en la base de referencia del Estudio Longitudinal de Salud entre Adultos brasileños (2008-2010) (ELSA-Brasil). Se realizó un análisis de regresión multinomial para probar la asociación entre AUS y el estado glucémico (GAA, TGA y de nuevo la diabetes tipo 2, diagnosticada en la cohorte como base de referencia) tras los ajustes por edad, sexo, color de piel, índice de masa corporal, actividad física, fumar, consumo de alcohol, comorbilidades, uso de medicinas. Se usó el modelo de regresión logística para evaluar la asociación entre AUS y la resistencia a la insulina por el HOMA-IR. Se realizó también un análisis estratificado por sexo. La media de edad (desviación estándar) fue 51,4 (8,9) años, un 55,2% de los participantes eran mujeres. Hubo 1.439 nuevos casos de diabetes diagnosticados. Tras todos los ajustes, una AUS más alta estuvo asociada con GAA, TGA y diabetes, con odds ratio (OR) = 1,15 (IC95%: 1,06; 1,25), 1,23 (IC95%: 1,14; 1,33), y 1,37 (IC95%: 1,24; 1,51), respectivamente. Hubo asociación entre los niveles AUS y la resistencia a la insulina con OR = 1,24 (IC95%: 1,13; 1,36). En el análisis estratificado por sexo, una AUS más alta persistía independientemente asociada con un estado glucémico alterado. Nuestros resultados sugieren que unos niveles más altos de AUS estuvieron significativamente asociados con el estado glucémico en una amplia población latinoamericana, principalmente entre mujeres.

Repercussões metabólicas: quais, como e por que investigar? / Metabolic repercussions: which ones, how and why investigate?

A síndrome dos ovários policísticos (SOP) é frequentemente acompanhada de distúrbio metabólico, principalmente dos carboidratos e dos lipídeos, aumentando o risco de síndrome metabólica. Por essa razão, alguns investigadores ainda denominam a SOP de síndrome metabólica-reprodutiva. O objetivo deste capítulo é descrever as principais repercussões metabólicas, bem como como investigá-las e saber como suas consequências podem ser deletérias para a saúde da mulher. Esta é uma revisão narrativa mostrando a implicação do metabolismo dos carboidratos e dos lipídeos nas dislipidemias, bem como da síndrome metabólica sobre o sistema reprodutor, e o risco cardiovascular da mulher com SOP. Conclui-se que o manejo adequado dos distúrbios metabólicos na SOP é benéfico a curto e a longo prazo tanto para o sistema reprodutor quanto para o cardiovascular.(AU)

Mala absorción de glucosa y de galactosa y su asociación con el síndrome de Down / Malabsorption of glucose and galactose and its relation with Down sydrome

Introducción: La malabsorción de glucosa y de galactosa es una enfermedad genética autosómica recesiva debida a una mutación que afecta al cotransportador de sodio-glucosa. Objetivo: Describir una asociación infrecuente entre el síndrome de Down y la mala absorción de glucosa y de galactosa. Presentación del caso: Niño desnutrido de 3 ½ meses de edad con síndrome de Down, de padres consanguíneos. Presentó precozmente diarrea explosiva, vómitos con deshidratación. Se mejoró tras la eliminación de la alimentación oral y la perfusión hidroelectrolítica y empeoró con la utilización de las sales de rehidratación oral y las fórmulas lácteas, sin proteínas de leche de vaca. El estudio de las heces mostró un pH fecal /5, presencia de glucosa, ionograma de las 24 horas fue: sodio 0,5 mEq (1-10), potasio 2,6 mEq (8-22) y el cálculo realizado para distinguir entre diferentes causas de diarrea dio aumentado: 168 mOsm/kg (50-125). Ante este cuadro clínico se consideró el diagnóstico de malabsorción de glucosa y de galactosa sobre todo tras la mejora de la sintomatología bajo dieta exclusivamente azucarada con fructosa. Conclusiones: Es importante tener en cuenta la malabsorción de glucosa y de galactosa dentro de los diagnósticos diferenciales de las diarreas acuosas congénitas. El diagnóstico precoz y la dieta adecuada con fructosa evitan deshidratación y malnutrición. La particularidad de nuestro caso es la asociación de la malabsorción de glucosa y de galactosa con el síndrome de Down, que, según nuestro conocimiento, es la primera vez que se describe y podría aumentar la morbilidad(AU)

Introduction: Malabsorption of glucose and galactose is a genetic autosomic recesive disease caused by a mutation that affects the co-transportator of sodium-glucose. Objective: To describe an unfrequent relation between the Down syndrome and the malabsortion of glucose and galactose. Case presentation: Undernourished child, 3 and half months old with Down syndrome from parents by blood. He early presented explosive diarrhea and vomiting with dehydration. He improved his state after elimination of oral feeding and a hydroelectrolitic perfusion, and his state worsened with the use of oral rehydration salts and dairy formula, even without cow´s milk proteins. The study of feces showed a fecal pH /5, presence of glucose, and the ionogram after 24 hours showed: sodium 0,5mEg (1-10), potasium 2,6 mEg (8-22) and the calculation made to identify the different causes of diarrhea was increased: 168 mOsm/kg (50-125). Having this clinical records, it was considered a diagnostic of glucose and galactose malabsorption, mainly after the improvement of the symptoms under a diet exclusively sugared with fructose. Conclusions: It is important to take into account glucose and galactose malabsortion in the differential diagnosis of congenital watery diahrrea. The early diagnosis and an adequate diet with fructose avoid dehytration and malnutrition. The particularity of this case is the relation of glucose and galactose malabsorption with Down syndrome, that according to our knowledge is the first time it is described and it can increase the morbility(AU)

Usando la curva de tolerancia a la glucosa para calcular el porcentaje relativo de sensibilidad insulínica y el porcentaje relativo de función beta insular / A program to estimate insulin resistance based on data from the oral glucose tolerance test

Background An instrument to help clinicians to evaluate the oral glucose tolerance test (OGTT) at-a-glance is lacking. Aim To generate a program written in HTML squeezing relevant information from the OGTT with glucose and insulin measurements. Material and Methods We reanalyzed a database comprising 90 subjects. All of them had both an OGTT and a pancreatic suppression test (PST) measuring insulin resistance directly. Thirty-seven of the 90 studied participants were insulin resistant (IR). Receiver operating characteristic (ROC) curves and Bayesian analyses delineated the diagnostic performances of four predictors of insulin resistance: HOMA, QUICKI, ISI-OL (Matsuda-DeFronzo) and I0*G60. We validated a new biochemical predictor, the Percentual Relative Insulin Sensitivity (%RIS), and calculated the Percentual Relative Beta Cell Function (%RBCF). Results The best diagnostic performance of the five predictors were those of the I0*G60 and the %RIS. The poorest diagnostic performances were those of the HOMA and QUICKI. The ISI-OL's performance was in between. The %RIS of participants with and without IR was 44.4 ± 7.3 and 101.1 ± 8.8, respectively (p < 0.05). The figures for % RBCF were 55.8 ± 11.8 and 90.8 ± 11.6, respectively (p < 0.05). Mathematical modeling of the relationship between these predictors and the Steady State Plasma Glucose Value from the PST was performed. We developed a program with 10 inputs (glucose and insulin values) and several outputs: I0*G60, HOMA, QUICKI, ISI-OL, Insulinogenic Index, Disposition Index, %RBCF, %RIS, and metabolic categorization of the OGTT (ADA 2003). Conclusions The OGTT data permitted us to write successfully an HTML program allowing the user to fully evaluate at-a-glance its metabolic information.

La amarga realidad de los edulcorantes no nutritivos: desde una perspectiva global al contexto chileno / The bitter reality of non-nutritive sweeteners: a global perspective applied to the Chilean context

Actualmente los edulcorantes no nutritivos (ENN) son ampliamente usados para endulzar los alimentos en reemplazo de los azúcares simples, con la ventaja de no aportar energía. A pesar de que en general no presentan efectos tóxicos, los estudios epidemiológicos no han podido evidenciar que su uso contribuya a mejorar la pérdida de peso, sino por el contrario, han revelado que los ENN pueden inducir alteraciones metabólicas como intolerancia a la glucosa. Estudios in vivo e in vitro han mostrado que muchos ENN activan a receptores del sabor dulce no sólo en los botones gustativos, sino que también en los receptores presentes en tejidos como el adiposo y pancreático, interfiriendo con su función normal. Además, el consumo ENN se ha asociado a alteraciones de la composición de la microbiota intestinal que conducen a una respuesta inflamatoria de bajo grado. La nueva evidencia disponible sobre los ENN hace necesario evaluar el uso cada vez más intenso de los ENN en Chile. Debido a que el gusto exacerbado por el sabor dulce que cultivamos desde la infancia es un potente catalizador del uso de ENN, proponemos que una oportuna educación del sentido del gusto puede contribuir a mejorar las elecciones alimentarias.

Currently, non-nutritive sweeteners (NNS) are widely used to sweeten foods instead of simple sugars, as they possess the advantage of not contributing to energy intake. Although they do not present toxic effects in general, epidemiological studies have not been able to show benefits when they are used in weight loss programs. However, they could induce metabolic alterations such as glucose intolerance. In vivo and in vitro studies have shown that many NNSs activate sweet taste receptors not only in the taste buds, but also in receptors present in adipose and pancreatic tissues, interfering with their normal function. In addition, NNS consumption has been associated with an alteration in the composition of the gut microbiota that leads to a low-grade inflammatory response. Due to the wide use of NNS in Chile, it is necessary to evaluate the potential health effects of using NNS in the Chilean population. We propose that a timely education of the sense of taste can contribute to moderating the preference for higher levels of sweet taste that humans develop in childhood, which could help to improve food choices.

Palmatine ameliorates high fat diet induced impaired glucose tolerance

BACKGROUND: The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. METHODS: Male Sprague-Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. RESULTS: Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased ß cell mass after the treatment of PAL. We further found out that PAL could alleviate the ß cell apoptosis that accounts for ß cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress ß cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the ß; cell apoptosis and JNK signaling in vitro. CONCLUSION: In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.

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.

Repercussões metabólicas e uso dos medicamentos sensibilizadores da insulina em mulheres com síndrome dos ovários policísticos / Metabolic repercussions and use of insulin-sensitizing drugs in women with polycystic ovary syndrome

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino-metabólico muito frequente no período reprodutivo. Quando associado ao distúrbio metabólico, as mulheres com SOP podem ter ainda risco acrescido para doença cardiovascular. O objetivo deste manuscrito é descrever as repercussões metabólicas, incluindo quais as principais, como investigar e as consequências desse distúrbio sobre a saúde da mulher. É uma revisão narrativa mostrando a implicação da resistência insulínica, das dislipidemias e da síndrome metabólica sobre o sistema reprodutor e sobre o risco cardiovascular da mulher com SOP, bem como do uso de sensibilizadores de insulina no seu tratamento. Conclui-se que a correção dos distúrbios metabólicos na SOP é benéfica tanto para o sistema reprodutor quanto para o cardiovascular. A primeira linha de tratamento é a mudança de estilo de vida e a perda de peso. Na resposta inadequada, o tratamento medicamentoso está recomendado. Nas mulheres com obesidade mórbida que não tiveram bons resultados com o tratamento clínico, a cirurgia bariátrica é uma opção.(AU)

Effect of Linagliptin versus Metformin on Insulin Secretion, Insulin Sensitivity and Glucose Control in Subjects with Impaired Glucose Tolerance / Efecto de la Linagliptina Frente a la Metformina en la Secreción de Insulina, Sensibilidad a la Insulina y Control de la Glucosa en Sujetos con Intolerancia a la Glucosa

ABSTRACT Aim: The aim of the study is to evaluate the effect of linagliptin versus metformin on insulin secretion, insulin sensitivity and glucose control in patients with impaired glucose tolerance (IGT). Patients and methods: A randomized, double-blind, clinical trial with parallel groups was per-formed on 16 adults with IGT. Lipid profile and haemoglobin (HbA1c) were evaluated prior to and after the intervention. Glucose and insulin were measured at 0, 30, 60, 90 and 120 minutes after a 75-g oral dextrose load. Eight patients received metformin (500 mg) twice a day before meals for three months. The remaining eight patients received placebo (500 mg) in the morning and linagliptin (5 mg) in the evening before meals. The area under the curve (AUC) of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were assessed. Results: After linagliptin administration, a significant decrease in glucose at 90 minutes (10.8 ± 2.6 vs 7.9 ± 2.2 mmol/L, p < 0.05), 120 minutes (8.8 ± 0.9 vs 6.5 ± 2.1 mmol/L, p < 0.05) and AUC of glucose (1168 ± 210 vs 953 ± 207 mmol/L, p < 0.05) were observed. Metformin administration decreased insulin significantly at 0 minutes (94.8 ± 25.8 vs 73.8 ± 24.6 pmol/L, p < 0.05). Conclusion: Three-month administration of linagliptin in patients with IGT decreased glucose at 90 and 120 minutes after a 75-g oral dextrose load and AUC of glucose. Metformin decreased insulin at 0 minutes.

RESUMEN Objetivo: El objetivo del estudio es evaluar el efecto de la linagliptina frente a la metformina en la secreción de insulina, la sensibilidad a la insulina, y el control de la glucosa en pacientes con intolerancia a la glucosa (IG). Pacientes y métodos: Se realizó un ensayo clínico aleatorio de doble ciego con grupos paralelos a 16 adultos con IG. El perfil lipídico y la hemoglobina (Hba1C) se evaluaron antes y después de la intervención. La glucosa y la insulina se midieron a los 0, 30, 60, 90 y 120 minutos después de un carga oral de 75-g dextrosa. Ocho pacientes recibieron metformina (500 mg) dos veces al día antes de las comidas por tres meses. Los ocho pacientes restantes recibieron placebo (500 mg) por la mañana y linagliptina (5 mg) por la noche antes de las comidas. El área bajo la curva (ABC) de la glucosa y la insulina, la secreción total de insulina, la primera fase de la secreción de insulina, y la sensibilidad a la insulina, fueron evaluadas. Resultados: Luego de la administración de la linagliptina, se observó una disminución significativa de la glucosa a los 90 minutos (10.8 ± 2.6 vs 7.9 ± 2.2 mmol/L, p < 0.05), 120 minutos (8.8 ± 0.9 mmol/L p < 0.05) y el ABC de la glucosa (1168 ± 210 vs 953 ± 207 mmol/L, p < 0.05). La administración de metformina redujo significativamente la insulina a los 0 minutos (94.8 ± 25.8 vs 73.8 ± 24.6 pmol/L, p < 0.05). Conclusión: Tres meses de administración de linagliptina en pacientes con IG disminuyó la glucosa a los 90 y 120 minutos después de una carga oral de dextrosa de 75-g y el ABC de la glucosa. La metformina disminuyó la insulina en 0 minutos.

Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China

ABSTRACT Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. Subjects and methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. Results: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. Conclusion: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.

Deficiência de vitamina D e menopausa: efeitos no fígado e no tecido adiposo periovariano de camundongos / Deficiency of vitamin d and menopause: effects on liver and periovarian adipose tissue of mice

No presente estudo, avaliamos o impacto da deficiência de vitamina D em camundongos fêmeas ovariectomizadas. A hipótese do nosso estudo é que a deficiência de vitamina D aumenta a inflamação no tecido adiposo e promove acúmulo de gordura hepática em modelo de menopausa. Camundongos C57BL/6 fêmeas, com três meses de idade, foram ovariectomizados ou não, e divididos em grupos controle (C, alimentado com dieta padrão), ovariectomizados (Ovx, alimentado com dieta padrão), controle sem vitamina D (C (D-), alimentado com dieta padrão sem vitamina D) e ovariectomizados sem vitamina D (Ovx (D-), alimentados com dieta padrão sem vitamina D) por doze semanas. Como resultados, no grupo Ovx (D-), houve resistência à insulina e intolerância à glicose, além do aumento da massa corporal. No fígado, houve aumento da esteatose hepática, com consequente aumento da lipogênese e inflamação, fatores que foram comprovados pelo aumento na expressão de genes e proteínas responsáveis pelo metabolismo lipídico. Além disso, houve redução da beta-oxidação de ácidos graxos. No tecido adiposo periovariano, a ovariectomia aumentou a área média dos adipócitos e a expressão proteica e gênica de citocinas pró-inflamatórias. Associado aos achados supracitados, houve aumento do metabolismo local da vitamina D, como forma de compensar a deficiência dessa vitamina. Em conclusão, os achados experimentais atuais são robustos e demonstram que a ovariectomia e a restrição dietética de vitamina D em camundongos têm efeitos adversos aditivos que levam a um aumento da massa corporal, da esteatose hepática e resistência à insulina. Esses achados estão ligados ao aumento dos marcadores de lipogênese e diminuição da beta-oxidação, predispondo ao acúmulo de gordura no fígado, assim como o aumento da inflamação no tecido adiposo periovariano.

In the present study, we have evaluated the impact of vitamin D deficiency in ovariectomized female mice. The hypothesis of our study is that vitamin D deficiency increases the inflammation in adipose tissue and promotes accumulation of hepatic fat in the menopause model. Female C57BL / 6 mice, three months old, were ovariectomized or not, and divided into control (C, fed control diet), ovariectomized (Ovx fed control diet), control without vitamin D (D-), fed control diet without vitamin D) and ovariectomized without vitamin D (Ovx (D-), fed control diet without vitamin D) for twelve weeks. As a result, in Ovx (D-) group there was insulin resistance and glucose intolerance, as well as an increase in body mass. In the liver, there was an increase in hepatic steatosis, with consequent increase in lipogenesis and inflammation due to the increase in the expression of genes and proteins of lipid metabolism. In addition, there was a reduction of beta-oxidation and reduction of fatty acid oxidation. In periovarian adipose tissue, ovariectomy increased the mean area of adipocytes and protein and gene expression of pro-inflammatory cytokines. Associated with the findings, there was increase in the local vitamin D metabolism, to compensate the deficiency of this vitamin. In conclusion, that current experimental findings are robust showing that ovariectomy and vitamin D dietary restriction in mice have additive adverse effects that lead to increased body mass, hepatic steatosis and insulin resistance. These findings are linked to increase of lipogenesis markers and decreased of beta-oxidation, predisposing to accumulation of fat in the liver, as well as increased inflammation in periovarian adipose tissue.

Evaluation of plaque characteristics in coronary artery patients with impaired glucose tolerance through optical coherence tomography

SUMMARY OBJECTIVE With the adoption of optical coherence tomography (OCT), this study targets the impacts on plaque characteristics brought about by impaired glucose tolerance (IGT) in patients with coronary artery disease. METHODS For this study, 150 patients with coronary artery disease were recruited. Regarding glycosylated hemoglobin (HbAlc), the patients were sectioned into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) groups. Coronary angiography (CAG) and OCT were conducted for 150 patients. RESULTS There were 186 plaques discovered in 150 patients (37, 40, 44, and 65 in the NGT, IFG, IGT, and DM groups, respectively). Compared to the NGT group, the lipid core size, which is presented as the average angle of the lipid arc, was markedly larger in the IFG,IGT and DM groups ( 135.7 ± 32.7 Ê, 161.2 ± 55.7 Ê, 162.5 ± 55.8 Ê, and 170.2 ± 59.7 Ê, respectively, all P values< 0.05). Meanwhile, the fibrous cap over the lipid core in the NGT group was remarkably thicker than that in the IFG, IGT, and DM groups (115.7 ± 47.7 μm vs. 77.7 ± 23.5 μm, 75.1 ± 23.2 µm, 71.2 ± 22.1 µm, all P values<0.05). CONCLUSION Coronary plaques in coronary artery patients with NDT are more stable than in those with IGT and DM.

RESUMO OBJETIVO Com a adoção da tomografia de coerência óptica (OCT), o presente estudo visa as características dos impactos na placa trazidos pela tolerância diminuída à glicose (IGT) em pacientes com doença na artéria coronária. MÉTODOS Cento e cinquenta doentes com doença arterial coronária foram recrutados para este estudo. De acordo com a hemoglobina glicosilada (HbAlc), os pacientes foram divididos em grupos: tolerância normal à glicose (NGT), diminuição da glicemia de jejum (IFG), diminuição da tolerância à glicose (IGT) e diabetes mellitus (DM). Angiografia coronária (CAG) e OCT foram conduzidas para 150 doentes. RESULTADOS Existem 186 placas descobertas em 150 doentes (37, 40, 44 e 65 nos grupos NGT, IFG, IGT e DM, respectivamente). Em relação ao grupo NGT, o tamanho do núcleo lipídico, que é apresentado como o ângulo médio do arco lipídico, foi significativamente maior nos grupos IFG, IGT e DM (135,7 ± 32,7 Ê, 161,2 ± 55,7 Ê, 162,5 ± 55,8 Ê, e 170,2 ± 59,7 Ê, separadamente, os valores de P<0,05). Entretanto, a tampa sobre o núcleo de lipídios fibrosos no grupo NGT estava bem mais grossa do que nos grupos IFG, IGT e DM (115,7 ± 47,7μm vs. 77,7 ± 23,5 μm, 75,1 ± 23,2 µm, 71,2 ± 22,1 µm, todos os valores de P<0,05). CONCLUSÃO Placas coronárias na artéria coronária de pacientes com NDT são mais estáveis do que em doentes com IGT e DM.

Conocimientos, prácticas y actitudes en pacientes con diabetes mellitus tipo 2 / Knowledge, Practices and Attitudes in patients with Type 2 Diabetes Mellitus

Antecedentes: La diabetes tipo 2 es uno de los mayores problemas para los sistemas de salud de Latinoamérica. La expectativa de su incremento se basa en la alta prevalencia de las condiciones que preceden a la diabetes como la obesidad y la intolerancia a la glucosa, entre otras. Objetivo: Determinar los conocimientos, prácticas y actitudes en relación a su enfermedad de los pacientes con Diabetes Mellitus tipo 2 en la aldea El Nance, Campamento, Olancho, Octubre-Diciembre 2016. Métodos: Estudio descriptivo que incluyó todos los pacientes con Diabetes Mellitus tipo 2 de la aldea el Nance, Campamento, Olancho. Se realizó una encuesta previa y luego se brindó educación a cada paciente. Resultados: Se evaluaron 40 pacientes con diabetes mellitus tipo 2, en donde 62.5 % desconoce que es hipoglicemia, la mitad de ellos relaciona las complicaciones a diabetes mellitus tipo 2 . 32.5% de los pacientes no realiza actividad física semanal. La mitad de ellos no cuenta con glucómetro. 55% de los pacientes asistiría a sus citas médicas si supiera que estará mejor. Discusión: Los pacientes diabéticos tipo 2 de este estudio presentaron conocimientos adecuados acerca de los conceptos de la enfermedad, las complicaciones, y algunas prácticas, siendo similar a los resultados de estudios centroamericanos.

Rimonabant improves metabolic parameters partially attributed to restoration of high voltage-activated Ca2+ channels in skeletal muscle in HFD-fed mice

Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising strategies for the treatment of obesity and other related metabolic disorders. Although CB1R inhibition may cause adverse psychiatric effects including depression and anxiety, the investigation of the role of peripheral CB1R on weight loss and related metabolic parameters are urgently needed. We first explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist, on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice. Then, real-time PCR and electrophysiology were used to explore the contribution of high voltage-activated Ca2+ channels (HVACCs), especially Cav1.1, on rimonabant's effect in skeletal muscle (SM) in HFD-induced obesity. Five-week HFD feeding caused body weight gain, and decreased glucose/insulin tolerance in mice compared to those in the regular diet group (P<0.05), which was restored by rimonabant treatment compared to the HFD group (P<0.05). Interestingly, HVACCs and Cav1.1 were decreased in soleus muscle cells in the HFD group compared to the control group. Daily treatment with rimonabant for 5 weeks was shown to counter such decrease (P<0.05). Collectively, our findings provided a novel understanding for peripheral CB1R's role in the modulation of body weight and glucose homeostasis and highlight peripheral CB1R as well as Cav1.1 in the SM as potential targets for obesity treatment.

Frecuencia de síndrome metabólico en niños y adolescentes del Paraguay / Frequency of metabolic syndrome in children and adolescents in Paraguay

La intención de la elección del tema de Síndrome Metabólico surge a raíz de la epidemia mundial de obesidad en la infancia y adolescencia observada en las últimas décadas, y que ha supuesto la aparición en pediatría de alteraciones hasta ahora más propias de la edad adulta, como el Síndrome Metabólico (SM) y que generen día a día numerosas complicaciones de salud como las Enfermedades Cardiovasculares (ECV) y Diabetes tipo 2. Se tienen como objetivo determinar la frecuencia de SM en niños y adolescentes del Paraguay y sus componentes. Se ha encontrado que el sobrepeso y la obesidad abdominal son los factores principales que contribuyen a las manifestaciones del Síndrome Metabólico en niños y adolescentes del Paraguay, por ese motivo corren mayor riesgo de sufrir enfermedades cardiovasculares y diabetes tipo 2 en el futuro y de forma más precoz. Se ha visto en estudios realizados en América que los componentes más prevalentes fueron la obesidad y la dislipidemia, mientras que; alrededor del 7% con hiperglucemia y síndrome metabólico de manera general. Según estudios realizados en Paraguay, se vio que la frecuencia de sobrepeso y obesidad es muy alta al igual que la incidencia del síndrome metabólico

The purpose of the choice of the Metabolic Syndrome issue arises from the worldwide epidemic of obesity in infancy and adolescence observed in the last decades, and which has led to the appearance in pediatrics of alterations that have hitherto been more typical of adulthood, Such as Metabolic Syndrome (MS) and that generate daily complications of health such as Cardiovascular Diseases (CVD) and Type 2 Diabetes. Its objective is to determine the frequency of MS in children and adolescents in Paraguay and its components. It has been found that overweight and abdominal obesity are the main factors that contribute to the manifestations of the Metabolic Syndrome in children and adolescents of Paraguay, for that reason they are at greater risk of suffering cardiovascular diseases and type 2 diabetes in the future and in a more early. It has been seen in studies carried out in America that the most prevalent components were obesity and dyslipidemia, whereas; around 7% with hyperglycemia and metabolic syndrome in general. According to studies in Paraguay, it was found that the frequency of overweight and obesity is very high, as is the incidence of the metabolic syndrome

Postpartum Reclassification of Glycemic Status in Women with Gestational Diabetes Mellitus and Associated Risk Factors / Reclassificação pós-parto do estado glicêmico em mulheres com diabetes mellitus gestacional e fatores de risco associados

Abstract Objective The aims of the study were to evaluate, after pregnancy, the glycemic status of women with history of gestational diabetes mellitus (GDM) and to identify clinical variables associated with the development of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Methods Retrospective cohort of 279 women with GDM who were reevaluated with an oral glucose tolerance test (OGTT) after pregnancy. Characteristics of the index pregnancy were analyzed as risk factors for the future development of prediabetes (IFG or IGT), and T2DM. Results: T2DM was diagnosed in 34 (12.2%) patients, IFG in 58 (20.8%), and IGT in 35 (12.5%). Women with postpartum T2DM showed more frequently a family history of T2DM, higher pre-pregnancy body mass index (BMI), lower gestational age, higher fasting and 2-hour plasma glucose levels on the OGTT at the diagnosis of GDM, higher levels of hemoglobin A1c, and a more frequent insulin requirement during pregnancy. Paternal history of T2DM (odds ratio [OR] =5.67; 95% confidence interval [95%CI] =1.64-19.59; p =0.006), first trimester fasting glucose value (OR =1.07; 95%CI =1.03-1.11; p =0.001), and insulin treatment during pregnancy (OR =15.92; 95%CI =5.54-45.71; p < 0.001) were significant independent risk factors for the development of T2DM. Conclusion A high rate of abnormal glucose tolerance was found in women with previous GDM. Family history of T2DM, higher pre-pregnancy BMI, early onset of GDM, higher glucose levels, and insulin requirement during pregnancy were important risk factors for the early identification of women at high risk of developing T2DM. These findings may be useful for developing preventive strategies.

Objetivo Os objetivos do estudo foram avaliar o estado glicêmico de mulheres com história de diabetes mellitus gestacional (DMG) após o parto e identificar fatores associados ao desenvolvimento de diabetes mellitus tipo 2 (DM2), glicemia de jejum alterada (GJA) e tolerância diminuída à glicose (TDG). Métodos Coorte retrospectiva de 279 mulheres com DMG reavaliadas com um teste oral de tolerância à glicose (TOTG) após a gestação. Foram analisados fatores prognósticos da gestação índice e fatores de risco para o futuro desenvolvimento de pré-diabetes (GJA ou TDG) e DM2. Resultados: Diagnosticou-se DM2 em 34 pacientes (12,2%), GJA em 58 (20,8%) e TDG em 35 (12,5%). Mulheres que evoluíram para DM2 apresentaram maior frequência de história familiar de DM2, índice de massa corporal (IMC) pré-gestacional mais elevado, menor idade gestacional, níveis superiores de glicemia de jejum e 2 horas após glicose no TOTG ao diagnóstico do DMG, hemoglobina glicada mais elevada, e uso mais frequente de insulina na gestação. História paterna de DM2 (odds ratio [OR] = 5,67; intervalo de confiança de 95% [IC95%] = 1,64-19,59; p = 0,006), glicemia de jejum do primeiro trimestre (OR = 1,07; IC95% = 1,03-1,11; p = 0,001) e o uso de insulina na gestação (OR = 15,92; IC95% = 5,54-45,71; p < 0,001) foram fatores de risco independentes para o desenvolvimento de DM2. Conclusão Houve elevada incidência de alterações no metabolismo da glicose em mulheres com DMG prévio. História familiar de DM2, IMC pré-gestacional elevado, DMG diagnosticado mais precocemente na gestação, com glicemias mais elevadas e necessidade de insulina, foram importantes fatores de risco associados à identificação precoce de mulheres com alto risco de desenvolvimento de DM2. Este conhecimento pode ser útil para o desenvolvimento de estratégias de prevenção.