La asociación del déficit de vitamina B12 y metformina / The association of vitamin B12 deficiency and metformin

La metformina es el agente antidiabético oral más utilizado para el tratamiento de la diabetes mellitus tipo 2 (DM2) y se ha descrito la asociación de su uso con el déficit de vitamina B12. Se realizó una revisión narrativa de estudios para conocer la evidencia de dicha asociación, y las recomendaciones para su pesquisa, prevención y tratamiento. La prevalencia informada del déficit de vitamina B12 en los pacientes tratados con metformina osciló entre el 5,8% y el 52% en las diferentes series. Los pacientes de mayor edad, aquellos que reciben metformina a altas dosis y por más tiempo, y los que no consumen alimentos de origen animal, son quienes presentan mayor riesgo de padecer este déficit. Se recomienda la determinación de vitamina B12 cada año en pacientes con DM2 tratados con metformina y la eventual reposición en caso de déficit. Si bien existe consenso sobre el tratamiento del déficit, aún falta evidencia que permita realizar la recomendación sobre el tratamiento preventivo.

Metformin is the most widely used oral antidiabetic agent for the treatment of type 2 diabetes (T2D) and the association of the use of this drug with vitamin B12 deficiency has been described. A review of studies was carried out to find out the evidence of this association and the recommendations for its detection, prevention and treatment. The reported prevalence of vitamin B12 deficiency in patients treated with metformin ranged from 5.8% to 52% in the different series. Older patients, those who received metformin at high doses and for a longer time, and those who do not consume food of animal origin, are those who are at greater risk of suffering from this deficit. The determination of vitamin B12 every 1 year is recommended in patients with T2D treated with metformin, and the eventual replacement in case of deficiency. Although there is consensus on the treatment of the deficit, there is still a lack of evidence to make recommendations on a preventive treatment

Estrategias para mitigar hipoglucemias y variabilidad glucémica / Strategies to mitigate hypoglycemia and glycemic variability

La última década se ha destacado por los importantes avances en el desarrollo de nuevas tecnologías para pacientes que viven con diabetes mellitus (DM). Las innovaciones han estado orientadas principalmente a: mejorar la calidad de vida, reducir el impacto que genera la ocurrencia de hipoglucemias y reducir la carga de la enfermedad colaborando en la toma diaria de decisiones1. El monitoreo continuo de glucosa (MCG) es una herramienta que ha experimentado un importante avance al aportar información dinámica del estado metabólico en los pacientes y permitir la toma de decisiones, demostrado por un control metabólico estable, menores excursiones glucémicas, y una reducción significativa en la aparición y gravedad de las hipoglucemias2-5. Las presentes recomendaciones tienen como objetivo brindar herramientas rápidas para la interpretación de datos metabólicos y la consiguiente toma de decisiones terapéuticas. A tal fin se realizó una exhaustiva revisión de las principales guías y recomendaciones vigentes; posteriormente, el Grupo de Trabajo adaptó esa información según una serie de preguntas con criterio clínico práctico. El avance de los MCG es innegable, no solo en el desarrollo tecnológico, sino que se han convertido en una herramienta educativa para las personas con DM, su entorno y el equipo de salud al posibilitar un ajuste dinámico del tratamiento, prevenir complicaciones agudas y mejorar la calidad de vida. En esta ecuación enfatizamos la importancia de la educación diabetológica continua de la persona con DM y su entorno, participando activamente en la toma de decisiones para, de esta manera, cumplir con los objetivos propuestos: mejorar la calidad de vida, reducir la carga de la enfermedad y disminuir las excursiones glucémicas agudas.

The last decade has been highlighted by important advances in the development of new technologies for patients living with diabetes. The innovations have been oriented above all to improve the quality of life, reduce the impact generated by the occurrence of hypoglycemia and reduce the burden of the disease by collaborating in daily decision-making1. Continuous glucose monitoring (CGM) is a tool that has undergone significant progress, providing dynamic information on the metabolic status of patients, allowing decision making, demonstrated by stable metabolic control, lower glycemic excursions and a significant reduction in the occurrence and severity of hypoglycemia2-5. The purpose of these recommendations, developed by members of the Innovation Committee of the Argentine Society of Diabetes, is to provide rapid tools for the interpretation of metabolic data and the subsequent therapeutic decisionmaking. To this end, an exhaustive review of the main current guidelines and recommendations has been carried out, later the working group adapted this information according to a series of questions with practical clinical criteria. The progress of CGMs is undeniable, not only in technological development, but it has become an educational tool for people with diabetes, their environment, and the health team, offering the possibility of a dynamic adjustment of treatment, prevention of acute complications and improving quality of life. In this equation, we emphasize the importance of continuous diabetes education for the person with diabetes and their environment, actively participating in decision-making, and in this way, meeting the proposed objectives: improving quality of life, reducing the burden of disease, and decreasing acute glycemic excursions.

La asociación del déficit de vitamina B12 y metformina / The association of vitamin B12 deficiency and metformin

Resumen La metformina es el agente antidiabético oral más utilizado para el tratamiento de la diabetes mellitus tipo 2 (DM2) y se ha descrito la asociación de su uso con el déficit de vitamina B12. Se realizó una revisión narrativa de estudios para conocer la evidencia de dicha asociación, y las recomendaciones para su pesquisa, prevención y tratamiento. La prevalencia informada del déficit de vitamina B12 en los pacientes tratados con metformina osciló entre el 5,8% y el 52% en las diferentes series. Los pacientes de mayor edad, aquellos que reciben metformina a altas dosis y por más tiempo, y los que no consumen alimentos de origen animal, son quienes presentan mayor riesgo de padecer este déficit. Se recomienda la determinación de vitamina B12 cada año en pacientes con DM2 tratados con metformina y la eventual reposición en caso de déficit. Si bien existe consenso sobre el tratamiento del déficit, aún falta evidencia que permita realizar la recomendación sobre el tratamiento preventivo.

Abstract Metformin is the most widely used oral antidiabetic agent for the treatment of type 2 diabetes (T2D) and the association of the use of this drug with vitamin B12 deficiency has been described. A review of studies was carried out to find out the evidence of this association and the recommendations for its detection, prevention and treatment. The reported prevalence of vitamin B12 deficiency in patients treated with metformin ranged from 5.8% to 52% in the different series. Older patients, those who received metformin at high doses and for a longer time, and those who do not consume food of animal origin, are those who are at greater risk of suffering from this deficit. The determination of vitamin B12 every 1 year is recommended in patients with T2D treated with metformin, and the eventual replacement in case of deficiency. Although there is consensus on the treatment of the deficit, there is still a lack of evidence to make recommendations on a preventive treatment.

Estrategias para mitigar hipoglucemias y variabilidad glucémica / Strategies to mitigate hypoglycemia and glycemic variability

Resumen La última década se ha destacado por los importantes avances en el desarrollo de nuevas tecnologías para pacientes que viven con diabetes mellitus (DM). Las innovaciones han estado orientadas principalmente a: mejorar la calidad de vida, reducir el impacto que genera la ocurrencia de hipoglucemias y reducir la carga de la enfermedad colaborando en la toma diaria de decisiones1. El monitoreo continuo de glucosa (MCG) es una herramienta que ha experimentado un importante avance al aportar información dinámica del estado metabólico en los pacientes y permitir la toma de decisiones, demostrado por un control metabólico estable, menores excursiones glucémicas, y una reducción significativa en la aparición y gravedad de las hipoglucemias2-5. Las presentes recomendaciones tienen como objetivo brindar herramientas rápidas para la interpretación de datos metabólicos y la consiguiente toma de decisiones terapéuticas. A tal fin se realizó una exhaustiva revisión de las principales guías y recomendaciones vigentes; posteriormente, el Grupo de Trabajo adaptó esa información según una serie de preguntas con criterio clínico práctico. El avance de los MCG es innegable, no solo en el desarrollo tecnológico, sino que se han convertido en una herramienta educativa para las personas con DM, su entorno y el equipo de salud al posibilitar un ajuste dinámico del tratamiento, prevenir complicaciones agudas y mejorar la calidad de vida. En esta ecuación enfatizamos la importancia de la educación diabetológica continua de la persona con DM y su entorno, participando activamente en la toma de decisiones para, de esta manera, cumplir con los objetivos propuestos: mejorar la calidad de vida, reducir la carga de la enfermedad y disminuir las excursiones glucémicas agudas.

Abstract The last decade has been highlighted by important advances in the development of new technologies for patients living with diabetes. The innovations have been oriented above all to improve the quality of life, reduce the impact generated by the occurrence of hypoglycemia and reduce the burden of the disease by collaborating in daily decision-making1. Continuous glucose monitoring (CGM) is a tool that has undergone significant progress, providing dynamic information on the metabolic status of patients, allowing decision making, demonstrated by stable metabolic control, lower glycemic excursions and a significant reduction in the occurrence and severity of hypoglycemia2-5. The purpose of these recommendations, developed by members of the Innovation Committee of the Argentine Society of Diabetes, is to provide rapid tools for the interpretation of metabolic data and the subsequent therapeutic decisionmaking. To this end, an exhaustive review of the main current guidelines and recommendations has been carried out, later the working group adapted this information according to a series of questions with practical clinical criteria. The progress of CGMs is undeniable, not only in technological development, but it has become an educational tool for people with diabetes, their environment, and the health team, offering the possibility of a dynamic adjustment of treatment, prevention of acute complications and improving quality of life. In this equation, we emphasize the importance of continuous diabetes education for the person with diabetes and their environment, actively participating in decision-making, and in this way, meeting the proposed objectives: improving quality of life, reducing the burden of disease, and decreasing acute glycemic excursions.

Monitoreo continuo de glucosa: indicaciones, interpretación de datos y toma de decisiones terapéuticas. Recomendaciones de expertos / Continuous glucose monitoring: indications, data interpretation and making therapeutic decisions. Expert recommendations

Las herramientas para evaluar el grado de control glucémico se modificaron últimamente. La emoglobina glicosilada (HbA1c), parámetro de referencia (gold standard), refleja el control glucémico de los últimos tres meses de manera retrospectiva, sin expresar la variabilidad glucémica. El automonitoreo glucémico capilar (AGC) brinda información inmediata y prospectiva, pero dispone de pocos datos glucémicos para generar promedios y desviaciones estándares representativas. No detecta tendencias y tiene limitaciones para obtener datos nocturnos o durante la actividad física. Es invasivo y muchas veces rechazado. Contrariamente, el monitoreo continuo de glucosa (MCG) mide la glucosa instantáneamente, y muestra sus tendencias y su variabilidad en forma continua, incorporando nuevas métricas de control. Mediante el perfil ambulatorio de glucosa (PAG) se analizan los patrones del control glucémico durante el sueño, los ayunos prolongados, la actividad física y las intercurrencias, expresándolos como curvas con sus desviaciones estándar durante períodos de horas (8 a 24 horas) o días (7, 14, 30 y 90 días). El PAG contiene las siguientes métricas: porcentaje de tiempo en rango TIR (del inglés, time in range), porcentaje de tiempo por encima del rango TAR (del inglés, time above range), porcentaje de tiempo por debajo del rango o hipoglucemia TBR (del inglés, time below range) y coeficiente de variabilidad (%CV). La información continua permite tomar decisiones inmediatas, ya sea con la ingesta de carbohidratos o con la aplicación de insulina. El MCG con terapéuticas insulínicas inyectables (TII) o bomba portable de insulina (BPI) es una herramienta muy útil y complementaria para el tratamiento de la diabetes mellitus tipo 1 (DM1) y la DM2 en la insulinoterapia. Su utilización se asoció con descensos significativos en la HbA1c, disminución de la variabilidad glucémica, reducción de las hipoglucemias totales y nocturnas, y mejoría de la calidad de vida en estos pacientes. Nuestro propósito como grupo de expertos es generar una guía práctica para regular la implementación del MCG.

The tools to assess the degree of glycemic control were modified lately. Glycosylated hemoglobin (HbA1c), the gold standard, reflects the glycemic control of the last 3 months retrospectively, without expressing glycemic variability. Selfblood glucose monitoring (SBGM) provides immediate and prospective information, but has little glycemic data to generate representative averages and standard deviations. It does not detect trends and has limitations to obtain nocturnal data or during physical activity. It is invasive and often rejected. On the contrary, continuous glucose monitoring (CGM), allows to measure glucose instantly, shows your trends and variability continuously, incorporating new control metrics. The ambulatory glucose profile (AGP) analyzes the patterns of glycemic control during sleep, prolonged fasting, physical activity and intercurrences, expressing them as curves with their standard deviations during periods of hours (8 to 24 hours) or days (7, 14, 30 and 90 days). The AGP contains the following metrics: percentage time in range (TIR), percentage time above range mg/dl (TAR), percentage time below range or hypoglycemia (TBR) and coefficient of variation (%CV). CGM with IIT or continuous subcutaneous insulin infusion (CSII), is a very useful and complementary tool for the treatment of DM1 and DM2 in insulin therapy. Its use was associated with significant decreases in HbA1c, decreased glycemic variability, reduction of total and nocturnal hypoglycemia and improvement of the quality of life in these patients. Our aim as a group of experts is to generate a practical guide to regulate the implementation of the CGM.

Diabetic encephalopathy: beneficial effects of supplementation with fatty acids ω3 and nordihydroguaiaretic acid in a spontaneous diabetes rat model.

BACKGROUND: Diabetic encephalopathy is a chronic complications of diabetes mellitus that affects the central nervous system. We evaluated the effect of ω3 and ω6 polyunsaturated fatty acids (PUFAs) supplementation plus the antioxidant agent nordihydroguaiaretic acid (NDGA) on the etiopathology of diabetic encephalopathy in eSS rats, a spontaneous model of type 2 diabetes. METHODS: One hundred twenty spontaneous diabetic eSS male rats and 38 non-diabetic Wistar, used as healthy control, received monthly by intraperitoneal route, ω3 or ω6 PUFA (6.25 mg/kg) alone or plus NDGA (1.19 mg/kg) for 12 months. Diabetic rats had a worse performance in behavioural Hole-Board test. Histopathological analysis confirmed lesions in diabetic rats brain tissues. We also detected low expression of synaptophysin, a protein linked to release of neurotransmitters, by immunohistochemically techniques in eSS rats brain. Biochemical and histopathological studies of brain were performed at 12th month. Biochemical analysis showed altered parameters related to metabolism. High levels of markers of oxidative stress and inflammation were detected in plasma and brain tissues. Data were analysed by ANOVA test and paired t test was used by comparison of measurements of the same parameter at different times. RESULTS: The data obtained in this work showed that behavioural, biochemical and morphological alterations observed in eSS rats are compatible with previously reported indices in diabetic encephalopathy and are associated with increased glucolipotoxicity, chronic low-grade inflammation and oxidative stress burden. Experimental treatments assayed modulated the values of studied parameters. CONCLUSIONS: The treatments tested with ω3 or ω3 plus NDGA showed improvement in the values of the studied parameters in eSS diabetic rats. These observations may form the basis to help in prevent and manage the diabetic encephalopathy.

Monitoreo continuo de glucosa: Utilidad e indicaciones / Continuous glucose monitoring. Utility and indications

Un adecuado control glucémico evita o retarda la aparición y/o evolución de las complicaciones crónicas en pacientes con diabetes mellitus (DM). Para lograrlo es necesario adecuar las dosis de insulina en personas con DM tipo 1 o tipo 2 en insulinoterapia, por el tradicional automonitoreo de glucosa capilar (AGC) que presenta aún limitaciones para generar un registro adecuado de datos, es invasivo y tiene baja adherencia. En contraposición, los nuevos sistemas de monitoreo continuo de glucosa (MCG) brindan una información más completa, más dinámica y con mejor tolerancia. Están constituidos por un sensor subcutáneo que informa ininterrumpidamente los niveles de glucosa del tejido celular subcutáneo y un módulo receptor que permite su lectura y almacenamiento. Los modelos de tiempo real (MCG-RT) permiten observar continuamente los datos, mientras que los sistemas intermitentes (MCG-Flash/EI) los muestran siempre y cuando se acerque el receptor al módulo sensor, generando una lectura voluntaria e intermitente, aunque almacenan todo en la memoria. El MCG informa además las tendencias glucémicas, indicando si están en ascenso o descenso y a qué velocidad cambian. El uso del MCG vs. AGC reduce la hemoglobina glicosilada (A1c) entre 0.53 y 1.0% con disminución significativa (38%) del tiempo de exposición a hipoglucemias. Presenta además, mayor adherencia. Los objetivos de esta revisión son: describir la homeostasis glucémica, evaluar la precisión del MCG, interpretar los datos adecuadamente y finalmente, sugerir en forma práctica los cambios para incorporar a la insulinoterapia tradicional, basados en la información que aportan estos novedosos sistemas de monitoreo.

An adequate glycemic control prevents and/or delays the development and/or progression of chronic complications in patients with diabetes mellitus (DM). To achieve this control, it is necessary to adjust insulin doses, in type 1 or insulinized type 2 DM persons, based on traditional capillary glucose self-monitoring, which has limitations to generate an adequate data record, is invasive and has low adherence. In contrast, new continuous glucose monitoring (CGM) systems provide more complete and dynamic information, and better compliance. In these systems, a subcutaneous sensor continuously sends glucose values which are captured and stocked by a receptor module. Real-time models (CGM-RT) allow continuous and real-time readings of interstitial glucose, whereas CGM-Flash/EI systems require lector approach to sensor module performing intermittent scanning. CGM shows if glycemic levels are increasing or decreasing and how fast it is happening (tendency). CGM decreases glycosylated hemoglobin between 0.53% and 1.0%, as well as time in hypoglycemia by 38%, increasing the time in range of glucose levels, in patients with high adherence. The objectives of this review are to describe the glycemic homeostasis, to evaluate the accuracy of the CGM to interpret the data adequately and finally, based on the information provided by these novel monitoring systems, to suggest a practical way to be added to the traditional intensive insulin therapy.

[Continuous glucose monitoring. Utility and indications]. / Monitoreo continuo de glucosa. Utilidad e indicaciones.

An adequate glycemic control prevents and/or delays the development and/or progression of chronic complications in patients with diabetes mellitus (DM). To achieve this control, it is necessary to adjust insulin doses, in type 1 or insulinized type 2 DM persons, based on traditional capillary glucose self-monitoring, which has limitations to generate an adequate data record, is invasive and has low adherence. In contrast, new continuous glucose monitoring (CGM) systems provide more complete and dynamic information, and better compliance. In these systems, a subcutaneous sensor continuously sends glucose values which are captured and stocked by a receptor module. Real-time models (CGMRT) allow continuous and real-time readings of interstitial glucose, whereas CGM-Flash/EI systems require lector approach to sensor module performing intermittent scanning. CGM shows if glycemic levels are increasing or decreasing and how fast it is happening (tendency). CGM decreases glycosylated hemoglobin between 0.53% and 1.0%, as well as time in hypoglycemia by 38%, increasing the time in range of glucose levels, in patients with high adherence. The objectives of this review are to describe the glycemic homeostasis, to evaluate the accuracy of the CGM to interpret the data adequately and finally, based on the information provided by these novel monitoring systems, to suggest a practical way to be added to the traditional intensive insulin therapy.

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

BACKGROUND: Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. METHODS: After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. RESULTS: Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. CONCLUSIONS: eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

Beneficial action of resveratrol: How and why?

Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKß/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.

Efecto sinérgico de ácidos grasos poliinsaturados (PUFAS) y ácidos nordihidroguaiaretico (NDGA) sobre parámetros metabólicos, inflamatorios y de oxidación celular en el desarrollo de diabetes espontánea de un modelo experimental

La Diabetes Mellitus (DM) es una enfermedad compleja con progresivas alteraciones en los parámetros metabólicos incluyendo también un estado de inflamación crónica sistémica de bajo grado, entre otros. La actividad física y la planificación nutricional son herramientas efectivas para prevenir y tratar la enfermedad y disminuir otros factores de riesgo relacionados, como el sobrepeso y obesidad. El modelo animal de ratas Stillman Salgado (ratas eSS) se basa en el empleo experimental de una variedad de ratas Wistar las cuales desarrollan espontánea y progresivamente una forma de DM, habitualmente con repercusiones clínicas y de laboratorio de leves a moderadas. Con la evolución de la DM, los animales muestran progresiva intolerancia a la glucosa, con aumento de los niveles plasmáticos de insulina, triglicéridos y glucosa, entre otros parámetros alterados. Es ampliamente conocido que los perfiles lipídicos influyen y son influidos por diversas patologías, como por ejemplo enfermedad Cardiovascular, DM, obesidad, entre otras. La relación entre la ingesta de ácidos grasos poli insaturados (PUFAs) de la serie omega 6/omega 3 (ω-6/ ω-3) menor a 4:1 se relaciona con bajos índices inflamatorios y de oxidación celular, hallándose en la dieta denominada “occidental” un desbalanceado consumo de carnes rojas, un disbalance en la alimentación respecto a estos PUFAs, con porcentajes aún mayores a 10:1, inclusive llegando a 40:1. Ello colabora para que se produzca un aumento progresivo de moléculas inflamatorias (eicosanoides en general) a partir de ácido araquidónico (AA), PUFAs ω-6, constituyendo la denominación común en estas entidades el establecimiento de inflamación crónica sostenida de bajo grado (CLGI)...

Diabetes Mellitus (DM) is a complex disease with alterations inmetabolic and inflammatory indices. Stillman Salgado rats (eSS rats) spontaneouslydevelop DM once reached middle age showing progressive impairment of glucosetolerance along with hypertriglyceridemia, hyperglycemia, and hyperinsulinemia. Inthe present study, we analyzed the effects of ω-3 and ω-6 polyunsaturated fatty acids(PUFAs) supplementation with or without nordihydroguaiaretic acid (NDGA), astrong, natural antioxidant and Lipooxygenase inhibitor molecule, isolated from nativeflora plants, on metabolic and inflammatory parameters in eSS rats to search whetherwhich combination may delay the development of DM and/or prevent its progression.MATERIALS AND METHODS: eSS rats after 10th days stopping breastfeed weremonthly administered intraperitoneal (IP) with ω-3 commercial fish oil (EPA 35% andDHA 40% 6,25mg/Kg) and purchased ω-6 (90% arachidonic acid 6,25mg/Kg)throughout twelve months. Two additional groups of rats received IP 1.9mg/KgNDGA along with w-3 and w-6 fatty acids. Blood and tissue samples were collectedto determine plasma TGs (TG), total plasma fatty acids (FA), A1C hemoglobin, Creactiveprotein (CRP), Gamma glutamyl transpeptidase (GGTP), lipo and hydroperoxides, nitrites and IL-6 (in plasma and in different organs as liver, kidney andpancreas) and then underwent oral glucose tolerance test (OGTT) as well...

Is insulin resistance a disorder of the brain?

There is reasonable evidence to suggest that insulin resistance may have its origins in the hypothalamus. Insulin secretion is regulated by sympathetic and parasympathetic nervous systems and modulates the concentrations of hypothalamic neuropeptides and monoaminergic neurotransmitters, and, in return, hypothalamic monoamines regulate the secretion of insulin by pancreatic beta cells. A lesion of the ventromedial hypothalamus produces all the features of the metabolic syndrome including insulin resistance and hyperinsulinemia. These and other evidence suggest that insulin resistance may very well be a disease of the brain.

L-arginine, NO and asymmetrical dimethylarginine in hypertension and type 2 diabetes.

Both hypertension and type 2 diabetes mellitus are common and there are no reliable markers either to predict their development or complications. High fat diet and carbohydrate-rich diet enhance serum asymmetrical dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric oxide synthesis. ADMA levels are elevated in patients with hypertension, poor control of hyperglycemia, diabetic microangiopathy and macroangiopathy and dyslipidemia. One of the earliest signs of vascular dysfunction and insulin resistance, which are present in hypertension and type 2 diabetes mellitus, is an elevation in serum ADMA levels. Displacing plasma ADMA by oral supplementation of L-arginine restores endothelial dysfunction by augmenting endothelial nitric oxide generation. Strict control of hyperglycemia decreases serum ADMA levels. These and other studies suggest that serum ADMA levels could be used to predict the development of hypertension and type 2 diabetes mellitus in those who are at high-risk to develop these diseases.

Role of PUFAs, the precursors of endocannabinoids, in human obesity and type 2 diabetes.

Polyunsaturated fatty acids (PUFAs) serve as precursors of the endocannabinoids (ECs) that are bioactive lipids molecules. Recent studies revealed that ECs participate in several physiological and pathological processes including obesity and type 2 diabetes mellitus. Here we review the experimental and clinical aspects of the role of endocannabinoids in obesity and type 2 diabetes mellitus and the modification of the endocannabinoids by exogenously administered PUFAs. Based on these evidences, we propose that the endocannabinoid system (ECS) can be modulated by exogenous manipulation of PUFAs that could help in the prevention and management of human diseases such as obesity, metabolic syndrome and type 2 diabetes mellitus.