10-day hyperlipidemic clamp in cats: effects on insulin sensitivity, inflammation, and glucose metabolism-related genes Abstract Obesity and hyperlipidemia are associated with impaired insulin sensitivity in human type 2 diabetes mellitus, possibly due to activation of a mild inflammatory response. Because obesity-induced insulin resistance predisposes cats to diabetes and because hyperlipidemia is a frequent concurrent finding, excess lipids may also impair insulin sensitivity in cats. Healthy cats (n=6) were infused with lipids (Lipovenoes 10%) for 10 days to clamp blood triglycerides at the approximate concentration of untreated feline diabetes (3-7 mmol/l). Controls received saline (n=5). On day 10, plasma adiponectin and proinflammatory markers were measured. Whole-body insulin sensitivity was calculated following an intravenous glucose tolerance test. Tissue mRNAs of glucose metabolism-related genes were quantified in subcutaneous and visceral fat, liver, and skeletal muscles. Accumulation of lipids was assessed in liver. At the termination of infusion, whole-body insulin sensitivity did not differ between groups. Compared to saline, cats infused with lipids had 50% higher plasma adiponectin and 2-3 times higher alpha(1)-acid glycoprotein and monocyte chemoattractant protein-1. Unexpectedly, lipid-infused cats had increased glucose transporter-4 (GLUT4) mRNA in the visceral fat, and increased peroxisome proliferative activated receptor-gamma2 (PPARgamma2) in subcutaneous fat; adiponectin expression was not affected in any tissue. Lipid-infused cats developed hepatic steatosis. Although hyperlipidemia induced systemic inflammation, whole-body insulin sensitivity was not impaired after 10 day infusion. Increased circulating adiponectin may have contributed to prevent insulin resistance, possibly by increasing GLUT4 and PPARgamma2 transcripts in fat depots. Obesity and hyperlipidemia are associated with impaired insulin sensitivity in human type 2 23

Type 2 diabetes mellitus (T2DM) is one of the largest health emergencies of the 21st century given the worldwide increase of obesity during the last decades and its close association. T2DM is an inherited, polygenic and chronic disease caused by the interaction between several genetic variants in genes and the environment. The continuous search for new and more effective tools to achieve appropriate glycemic control became imperative in order to reduce long-term complications and mortality rates related to T2DM. Treatment options includes lifestyle modifications and several pharmacotherapies as first step in the therapeutical algorithm, but high corps of evidence have shown that gastrointestinal (GI) operations, especially those that involve food rerouting through the GI tract, are safe interventions and achieve superior outcomes for improvement in glucose metabolism when comparing with optimal medical and lifestyle changes. GI Surgery, specially Roux-en-Y gastric bypass (RYGB), is currently the most accepted surgical procedure to treat T2DM, and has also demonstrated to reduce significantly other cardiovascular risk factors (lipids and blood pressure control) when compared with optimal medical treatment, with good long-term effects on cardiovascular risks and mortality. Although the most effective technique in achieving diabetes remission is biliopancreatic diversion, the effectiveness-adverse effects balance is superior for RYGB. For these reasons, metabolic surgery (which was defined as "the operative manipulation of a normal organ or organ system to achieve a biological result for a potential health gain") has been considered and accepted as a new step in the therapeutic algorithm for T2DM when optimal lifestyle and medical interventions don't achieve optimal glycemic goals. for T2DM are glycated hemoglobin (A1c) <7%, low-density lipoprotein cholesterol levels <100 mg/dL and blood pressure <130-80 mmHg (3,6), and less than 20% of USA patients achieve these levels in triple target despite having the best medical treatment. Bariatric surgery was first described just for reducing weight in severely obese patients. A Swedish Obese Subjects (SOS) study, demonstrated that the surgery group arm not only had more drastic and sustainable average reduction of excess body weight but also had remarkable beneficial effects on cardiovascular risk factors, such as waist circumference, blood pressure, glucose and insulin levels, uric acid, triglyceride and HDL cholesterol levels when compared with conventionally treated patients (7-10). Even though the SOS study showed a reduction of the number of cardiovascular events and overall mortality in the surgery group (HR 0.76, CI 95%) (11,12), one of the most relevant points was the finding of absence of significant relationship between cardiovascular mortality and body mass index (BMI) (7,13).Gastrointestinal (GI) operations have demonstrated, especially those that involve food rerouting through the GI tract that are safe and provide better outcomes for weight loss and...

Introducción: la creciente pandemia de obesidad y diabetes tipo 2 (DM2) demanda opciones terapéuticas más efectivas para lograr un adecuado control metabólico y disminuir la morbimortalidad cardiovascular en este grupo de pacientes. En este contexto, la cirugía metabólica (CM) constituye una herramienta innovadora, segura y eficaz que complementa pero no reemplaza a los cambios necesarios del estilo de vida y tratamiento médico.Objetivos: el objetivo del Consenso es la fundamentación y acuerdo de utilización de una técnica quirúrgica, específicamente el Bypass Gástrico en Y de Roux (BPGYR), en el tratamiento de pacientes con DM2 que presentan un índice de masa corporal (IMC) entre 30-35 kg/m2 e inadecuado control metabólico.Conclusiones: el Consenso Argentino de Cirugía Metabólica elaborado por la Sociedad Argentina de Diabetes (SAD), la Sociedad Argentina de Nutrición (SAN) y la Sociedad Argentina de Cirugía de la Obesidad (SACO) expresa la opinión de expertos sobre la evidencia científica disponible y propone considerar a la CM en el algoritmo terapéutico de pacientes con DM2 e IMC 30-35 kg/m2 que no logran adecuado control metabólico con tratamiento médico convencional. Se describen los criterios a tener en cuenta en la selección de pacientes para CM, y se destaca el rol del equipo multidisciplinario liderado por médicos especialistas en enfermedades endocrino- metabólicas en la selección, evaluación, preparación y seguimiento de estos pacientes.

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La enfermedad del hígado graso no alcohólico (EHGNA) es una enfermedad del hígado que no se asocia con el alcohol. Su prevalencia aumenta junto con la epidemia de obesidad y diabetes tipo 2 (DM2), y el riesgo de sufrir una enfermedad hepática más agresiva es mayor con el consiguiente aumento de la cirrosis, el carcinoma hepatocelular y la enfermedad cardiovascular (ECV). La acumulación ectópica de grasa se asocia a dietas hipergrasas y de alta densidad energética, a la hiperglucemia y la insulinorresistencia que condicen a la supresión de la producción hepática de glucosa y la disminución de la captación de glucosa por el músculo esquelético lo cual promueve la lipogénesis de novo y genera un círculo vicioso que favorece aún más la esteatosis.