Alteraciones hemorreológicas, fibrinolíticas e hipercoagulabilidad en la obesidad: Efecto de la pérdida ponderal.

RESUMEN Se ha demostrado que la obesidad es un factor de riesgo. Los factores de riesgo cardiovascular clásicos asociados a la misma no pueden explicar por sí solos todo el exceso de eventos cardiovasculares que presentan estos pacientes. Por otra parte, varios estudios han evidenciado la asociación entre obesidad y tromboembolismo venoso. Los mecanismos a través de los cuales la obesidad predispone de forma independiente a las complicaciones trombóticas tanto arteriales como venosas se desconocen. Las alteraciones hemorreológicas podrían inducir un estado protrombótico en la obesidad. Dentro de éstas, la agregación y la deformabilidad eritrocitarias han sido las menos estudiadas en el paciente obeso. Asimismo, la expresión de fosfatidilserina en la hoja externa de la bicapa como posible mecanismo protrombótico ha sido escasamente valorada en estos pacientes. De igual manera, ciertas alteraciones del sistema de la proteína C pueden asociarse con un aumento del riesgo trombótico. Adicionalmente, un elevado nivel del inhibidor del activador tisular del plasminógeno de tipo 1 (PAI-1) puede contribuir al estado de hipercoagulabilidad, pudiendo dichos niveles relacionarse con el polimorfismo genético 4G/5G de su gen. Nuestra hipótesis de trabajo fue que el estado protrombótico asociado a la obesidad podría deberse, entre otras causas, a alteraciones hemorreológicas, fibrinolíticas y del sistema de la proteína C, siendo estas alteraciones subsidiarias de mejoría con la pérdida ponderal obtenida mediante tratamiento dietético. Tras estudiar a 67 pacientes obesos y compararlos con un grupo control, y someterlos a dieta hipocalórica durante tres meses, obtuvimos las siguientes conclusiones: Los pacientes obesos presentan un perfil hemorreológico alterado, caracterizado por un aumento de los niveles de fibrinógeno, de la viscosidad plasmática, de la viscosidad sanguínea a hematocrito corregido, y de la agregabilidad eritrocitaria. Esta hiperagregabilidad parece deberse a la resistencia insulínica asociada a la obesidad. La deformabilidad eritrocitaria no se encuentra disminuida en los pacientes obesos, posiblemente debido a la ausencia de alteraciones en el contenido en colesterol y fosfolípidos de la membrana eritrocitaria. Sin embargo, los pacientes obesos con síndrome metabólico presentan una menor deformabilidad eritrocitaria. Los niveles aumentados de fibrinógeno, de viscosidad plasmática y de viscosidad sanguínea no se modifican con la pérdida de peso. Sin embargo, la agregabilidad eritrocitaria mejora de forma significativa. Como hallazgo no descrito hasta el momento actual, hemos encontrado un aumento de la expresión de fosfatidilserina en la hoja externa de la membrana eritrocitaria en los pacientes obesos. No hemos encontrado en los pacientes obesos un estado de resistencia a la proteína C activada adquirida. Los niveles de proteína C activada están aumentados en los pacientes obesos. Tras la pérdida de peso, hemos observado una disminución de los niveles de proteína C activada. Los pacientes obesos presentan una hipofibrinolisis manifestada por un aumento de los niveles de PAI-1 antigénico y funcional. No se ha encontrado en estos pacientes una asociación significativa entre dichos niveles y la presencia del alelo 4G. Los pacientes obesos con síndrome metabólico muestran una tendencia no significativa a presentar cifras mayores de PAI-1. Tras la pérdida de peso, se observa una disminución significativa de los niveles de PAI-1. Se observa una tendencia no significativa en los pacientes obesos portadores del alelo 4G a un menor descenso de PAI-1 en respuesta a la pérdida de peso. Como conclusión final, hemos evidenciado alteraciones hemorreológicas, fibrinolíticas y de la hemostasia asociadas a la obesidad. Algunas de estas alteraciones han mejorado de forma significativa con la pérdida de peso, lo que podría ayudar a reducir el riesgo trombótico de estos pacientes. __________________________________________________________________________________________________Obesity is considered to be an independent risk factor for arterial and venous thrombosis. The mechanisms through which obesity increases cardiovascular risk independently of its association with other cardiovascular risks factors are not well established. Hemorheological factors could contribute to this prothrombotic state. Erythrocyte deformability, erythrocyte aggregation and lipidic membrane phosphatidylserine expression have been scarcely studied in these patients. Disturbances in C protein system could favour as well thrombotic events. An increase in plasminogen activator inhibitor type 1 levels (PAI-1), which can be related to 4G/5G polymorphism of its gene, can also contribute to this hypercoagulable state. Our objective was to show that hemorheological, fibrynolitic and coagulation disturbances can contribute to the hypercoagulable state in obesity, and that these disturbances can improve with weight loss. We studied 67 obese patients who were compared with a control group, and underwent a hypocaloric diet for three months. The results were as follows: Obese patients show a disturbed hemorheological profile, with an increase in fibrinogen, plasma and blood viscosity, and erythrocyte aggregability. This hyperaggregability is associated to insulin resistance. Erythrocyte deformability is not decreased in obese patients, and no changes in cholesterol and phospholipids membrane content are found. Nevertheless, obese patients with metabolic syndrome show lower erythrocyte deformability. High levels of fibrinogen and blood and plasma viscosity do not change with weight loss, but hyperaggregability improves. Phosphatidylserine expression in the outside lawyer of lipidic membrane is increased in obese patients. We have not found a state of activated protein C resistance in obese patients. Activated protein C levels are increased in obese patients, and decrease with weight loss. Obese patients show an increase in PAI-1 antigen and activity. We have not found a correlation between these levels and 4G allele. Obese patients with metabolic syndrome have non-significantly higher levels of PAI-1. After weight loss, PAI-1 levels decrease. Obese patients with 4G allele show a non significant lower decrease of PAI-1 levels. We have confirmed hemorheological, fibrinolytic and coagulation disturbances associated to obesity. Some of these disturbances improve with weight loss

Type 1 diabetes mellitus and periodontal disease : relationship to different clinical variables

Objective: This study is designed to evaluate the frequency of periodontal disease in a group of patients with type 1 diabetes mellitus and how this relates with diabetes metabolic control, duration of diabetes, and presence of diabetic complications. Methods: A comparison was made of periodontal parameters (plaque index, bleeding index, pocket depth and attachment loss) in a group of diabetic patients (n=90) versus a group of non-diabetics (n=90). Logistic regression analysis was performed to evaluate relationship between periodontal parameters and degree of metabolic control, the duration of the disease, and the appearance of complications. Results: Diabetics had greater bleeding index (p<0.01), deeper periodontal pockets (p<0.01) and more periodontal attachment loss (p<0.01) than non-diabetics. Deficient metabolic control and presence of diabetic complication were associated with higher bleeding index and pocket depth (p?0.02). Conclusions: Patients with type 1 diabetes appear to show increased periodontal disease susceptibility, particularly those with poorer metabolic control or with diabetic complications

Insulin Withdrawal in Diabetic Kidney Disease: What Are We Waiting for?

The prevalence of type 2 diabetes mellitus worldwide stands at nearly 9.3% and it is estimated that 20–40% of these patients will develop diabetic kidney disease (DKD). DKD is the leading cause of chronic kidney disease (CKD), and these patients often present high morbidity and mortality rates, particularly in those patients with poorly controlled risk factors. Furthermore, many are overweight or obese, due primarily to insulin compensation resulting from insulin resistance. In the last decade, treatment with sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to be beneficial in renal and cardiovascular targets; however, in patients with CKD, the previous guidelines recommended the use of drugs such as repaglinide or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), plus insulin therapy. However, new guidelines have paved the way for new treatments, such as SGLT2i or GLP1-RA in patients with CKD. Currently, the new evidence supports the use of GLP1-RA in patients with an estimated glomerular filtration rate (eGFR) of up to 15 mL/min/1.73 m2 and an SGLT2i should be started with an eGFR > 60 mL/min/1.73 m2. Regarding those patients in advanced stages of CKD, the usual approach is to switch to insulin. Thus, the add-on of GLP1-RA and/or SGLT2i to insulin therapy can reduce the dose of insulin, or even allow for its withdrawal, as well as achieve a good glycaemic control with no weight gain and reduced risk of hypoglycaemia, with the added advantage of cardiorenal benefits

Insulin withdrawal in diabetic kidney disease : What are we waiting for?

The prevalence of type 2 diabetes mellitus worldwide stands at nearly 9.3% and it is estimated that 20-40% of these patients will develop diabetic kidney disease (DKD). DKD is the leading cause of chronic kidney disease (CKD), and these patients often present high morbidity and mortality rates, particularly in those patients with poorly controlled risk factors. Furthermore, many are overweight or obese, due primarily to insulin compensation resulting from insulin resistance. In the last decade, treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to be beneficial in renal and cardiovascular targets; however, in patients with CKD, the previous guidelines recommended the use of drugs such as repaglinide or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), plus insulin therapy. However, new guidelines have paved the way for new treatments, such as SGLT2i or GLP1-RA in patients with CKD. Currently, the new evidence supports the use of GLP1-RA in patients with an estimated glomerular filtration rate (eGFR) of up to 15 mL/min/1.73 m2 and an SGLT2i should be started with an eGFR > 60 mL/min/1.73 m2. Regarding those patients in advanced stages of CKD, the usual approach is to switch to insulin. Thus, the add-on of GLP1-RA and/or SGLT2i to insulin therapy can reduce the dose of insulin, or even allow for its withdrawal, as well as achieve a good glycaemic control with no weight gain and reduced risk of hypoglycaemia, with the added advantage of cardiorenal benefits

Obesity and overweight prevalences in rural and urban populations in East Spain and its association with undiagnosed hypertension and Diabetes Mellitus: a cross-sectional population-based survey

Abstract Background An increase in the number of overweight and obese subjects in the general population has been observed. The aim of this study was to determine the prevalence of overweight and obese subjects in the general population and its association with undiagnosed pathologies, such as diabetes mellitus [DM] and hypertension [HT], by taking age, gender and place of residence [rural or urban] into account. Findings A cross-sectional population-based survey was conducted in Castellón, East Spain in 2005–2006. The sample included 2,062 participants aged 18–94 years. Weight, height, blood pressure and glycaemia values were recorded, and information about gender, age and place of residence was obtained. Overweight, obesity, and undiagnosed HT and DM prevalences were calculated. Multiple regression analyses were done to assess the association of overweight/obesity with undiagnosed HT and DM by adjusting for age, gender and place of residence. The overall overweight, obesity, and undiagnosed HT and DM prevalences were 39.9% [95% CI:37.3–42.0], 25.9% [95% CI:24.0–27.9], 9.0% [95% CI:7.8–10.4] and 12.6% [95% CI:11.2–14.1], respectively. We identified various independent risk factors; those relating to overweight were increasing age, male gender and rural residential area, while that relating to obesity was increasing age. Compared to normal weight adults, the Relative Prevalence Ratio (RPR) for subjects who were overweight and had HT was 2.00 [95% CI:1.21–3.32]; that for obesity and HT was 1.91 [95% CI:1.48–2.46], and it was 1.50 [95% CI:1.25–1.81] for obesity and DM. Conclusion Overweight and obesity prevalences, and their association with undiagnosed DM and HT, are high in our study population.</p