iSGLT2 y su potencial efecto nefroprotector en pacientes con diabetes mellitus 2 / iSGLT2 and its potential nephroprotector effect in patients with diabetes mellitus 2

Resumen: La diabetes mellitus 2 es una epidemia mundial, aunado a esto, la nefropatía diabética se ha convertido en la principal causa de insuficiencia renal en etapa terminal. En los pacientes con diabetes mellitus 2 existe sobreexpresión de los cotransportadores de glucosa ligados a la vía del sodio tipo 2 (SGLT2) que contribuyen al mantenimiento de la hiperglucemia. Por tanto, los inhibidores de este transportador representan un tratamiento innovador independiente de la acción de la insulina o la función de las células beta pancreáticas. En estudios recientes se ha demostrado que los iSGLT2 tienen efectos benéficos en la microvasculatura, en especial en la progresión de la nefropatía diabética. Este efecto no sólo se debe a la mejora del control glucémico, sino también a efectos directos en el riñón. Los iSGLT2, al inducir la glucosuria, revierten la glucotoxicidad renal. En estudios experimentales se ha observado que, además, se reduce la hiperfiltración, así como los marcadores inflamatorios y fibróticos. También se ha visto reducción del volumen circulante efectivo y aumento en la actividad de bloqueadores del sistema renina-angiotensina-aldosterona (bloqueadores RAA) circulantes, creando así un efecto nefroprotector.

Abstract: Type 2 diabetes mellitus 2 (DM2) is already a worldwide epidemic, in addition, diabetic nephropathy has become the leading cause of end-stage renal failure. In patients with DM2 there is an increased expression of the sodium-glucose cotransporters 2 (SGLT2) that contribute to the maintenance of hyperglycemia. Therefore, the inhibitors of this transporter represent an innovative therapy independent of the action of insulin or the function of pancreatic beta cells. Recent studies have shown that iSGLT2 have beneficial effects on microvasculature, especially in the progression of diabetic nephropathy. This effect is due not only to improved glycemic control but also to direct effects on the kidney. iSGLT2 induce glycosuria to reverse renal glucotoxicity. In experimental studies it has been observed that, in addition, hyper-filtration as well as inflammatory and fibrotic markers are reduced. There has also been a reduction in effective circulating volume and an increase in the activity of circulating renin-angiotensin-aldosterone system blockers (RAA blockers), thus creating a nephroprotective effect.

[Migration from a rural zone to an urban one is associated with android distribution of body fat in obese women]. / La migración de zona rural a urbana se asocia con la distribución androide de grasa corporal en mujeres obesas.

INTRODUCTION: Studies about migration to industrialized countries have shown an increased prevalence of diabetes, obesity and dyslipidaemias, all of them related to android body fat distribution. Migration status might be influence body fat distribution but it has not been sufficiently investigated. The aim of this study is to determine the relationship between body fat distribution and migration from rural to urban areas in Mexico. MATERIAL AND METHODS: This sequential sample of 433 women were seen in the outpatient obesity clinic of four federal states: Tabasco (n = 81), Mexico City (n = 166), Coahuila (n = 80), and Yucatan (n = 106). Migration history from rural to urban area, familial history of diabetes, ages of onset of obesity, height and weight circumferences were obtained. A regression logistic model was used and maintained as dependent variable body fat distribution. Age and federal state were considered as confounders and they adjusted the model. RESULTS: Migrating women from rural to urban area were 121 (27.9%). The waist circumference was higher in Tabasco (102.2 +/- 12 cm), and lesser in Yucatan (93.6 +/- 15 cm, p < 0.001); no differences were found for hip circumference. The logistic regression model showed that body fat distribution is associated to migration from rural to urban area, and also to diabetes of mother and age of onset of obesity. CONCLUSIONS: Migrating from rural to urban area is a risk factor for android body fat distribution and this risk increases with age, history of diabetes in mother and adulthood onset o obesity.

Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study.

Mixed hyperlipidemia is a common risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of ciprofibrate versus gemfibrozil for the treatment of patients with mixed hyperlipidemia carefully selected for similar lipid profiles. A total of 68 patients who had mixed hyperlipidemia after following an isocaloric American Heart Association (AHA) phase I diet for 4 weeks were included. The plasma lipid levels at the inclusion were low-density lipoprotein-cholesterol (LDL-C) > or = 130 mg/dL, cholesterol > or = 240 mg/dL, and triglycerides > or = 200 mg/dL. Patients were randomly assigned to receive ciprofibrate 100 mg/d or gemfibrozil 1,200 mg/d. At the end of the 8-week treatment period, efficacy and safety parameters were compared with baseline values. The primary efficacy parameters of the study were percentage changes in triglycerides and LDL-C from baseline. After 8 weeks, plasma triglyceride concentrations were decreased by 43.5% and 54% compared with baseline during ciprofibrate and gemfibrozil therapy, respectively (P <.001). High-density lipoprotein-cholesterol (HDL-C) concentrations were increased 20.8% and 19.3% during ciprofibrate and gemfibrozil, respectively (P <.001). Apoprotein B, cholesterol, and very-low-density lipoprotein-cholesterol (VLDL-C) concentrations were also improved by the study drugs (18.6%, 13.2%, and 30.9%, respectively, during ciprofibrate and 44%, 13.8%, and 14.4%, respectively, during gemfibrozil). Meanwhile, the effect of the drug was minimal on LDL-C. A significant decrease in non-HDL-C resulted from both treatments (19% and 19.5%, respectively, P <.05). The only statistically significant difference observed between treatments was the effects on fibrinogen concentration, a coronary risk factor. Ciprofibrate significantly decreased its concentration by 18.8%, fibrinogen was slightly increased during gemfibrozil treatment. No patient had a significant modification on any of the safety tests. In summary, ciprofibrate and gemfibrozil are well-tolerated and efficacious treatments for mixed hyperlipidemia. Significant reductions in triglycerides, non-HDL-C, and apolipoprotein B were achieved with both drugs. A significant fibrinogen reduction was obtained with ciprofibrate.

Prevalence of coronary artery disease risk factors in workers at the general hospital of Mexico of the ministry of health.

OBJECTIVE: To assess the prevalence of coronary risk factors in 2,463 health-care workers at the General Hospital of Mexico. METHODS: The study participants--1,620 women (65.8%) and 843 men (34.2%)--ranged in age from 16 to 65 years old. Study subjects were classified into five occupational subgroups: maintenance workers, 477 (19.4%); administrators, 697 (28.3%); physicians, 495 (20.1%); nursing staff, 559 (22.7%); and students, 235 (9.5%). For each participant, a clinical history was elicited, anthropometric determinations were done, and samples were obtained for determining blood glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels. RESULTS: Cholesterol levels above 6.2 mmol/L (>240 mg/dL) were found in 14.9% of the women and 14.8% of the men in the overall study group. Triglyceride levels of more than 2.25 mmol/L (>200 mg/dL) were found in 471 participants (19.1%). The prevalence of obesity was 13.5%, and high blood pressure was detected in 22.2% of study participants. Only 32.2% of subjects engaged in physical exercise one or more times per week; moreover, 32% of those surveyed smoked. The prevalence for diabetes mellitus was 6.25%. The multifactorial coronary risk index was high in 13.2% of men and 43.2% of women older than 30 years of age. CONCLUSION: This study confirmed the high prevalence of risk factors for cardiovascular diseases in personnel of the General Hospital of Mexico. Because many of these risk factors are modifiable, educational efforts and preventive measures should be implemented.

[The prevalence of risk factors for coronary disease in workers of the Hospital General de México]. / Prevalencia de factores de riesgo de enfermedad coronaria en trabajadores del Hospital General de México.

OBJECTIVE: To evaluate the prevalence of risk factors of coronary heart disease in the personnel of the General Hospital in Mexico City. MATERIAL AND METHODS: We studied 2,228 workers, 1,531 female (68.7%) and 697 male (31.2%) whose ages ranged from 16 to 65 years old in the period of 1993 to 1995. They were divided in work areas: Intendancy 477 (21.4%), Administrative, 697 (31.2%), Physicians, 495 (22.2%) and Nurses, 559 (25.0%). We collected clinical histories, anthropometric measures, and laboratory determinations of glucose, total cholesterol, LDL, HDL and triglicerydes. RESULTS: We found that 367 (14.9%) had total cholesterol above 240 mg/dl, with high values in females of the administrative area (17.1%) and males in the nursing department (26%), which was the highest tendency. Trigliceryde levels above 200 mg/dl were found in 208 males (24.6%) and 263 females (16.2%), with high prevalence in the nursing and administrative departments, in males (39.1 and 34.1% respectively). Obesity was present in 236 females (14.5%) and 97 males (11.5%). High blood pressure in 549 individuals (22.2%), 297 females (18.3%) and 252 males (29.8%) without significance regarding to work area. Smoking habits were positive in 32% of the total with highest prevalence in males from 30 to 45 years and in females from 30 to 50 years. We found an incidence of 6.24% of diabetes in all the subjects studied, 2.27% ignored the diagnosis at the moment they were studied. CONCLUSIONS: In this study we confirmed the high prevalence of risk factors of coronary heart disease in personnel of the General Hospital in Mexico City. In most cases, these risk factors that can be modified and, therefore, prevented.

[The efficacy, safety and tolerance of fluvastatin sodium 40 mg in patients with hyperlipidemia type IIA]. / Eficacia, seguridad y tolerabilidad de la fluvastatina sódica 40 mg en pacientes con hiperlipidemia tipo IIA.

Fluvastatin sodium is the first wholly synthetic 3 hydroxy-3-methylglytary 1 coenzyme A reductase inhibitor. It reduces cholesterol synthesis, enhances low density lipoprotein catalysis and hepatocyte LDL receptor expression. To evaluate the efficacy, tolerability and safety of fluvastatin sodium 40 mg once a day, we studied 40 patients with type IIA dyslipidemia. We observed a statistically significant reduction in total cholesterol (20.7%, p < 0.01), low density lipoprotein cholesterol (29.5%, p < 0.01), triglycerides (10.56%, p N.S.), very low density lipoprotein cholesterol (10.56%, p N.S.), C-LDL:C-HDL (33.7%, p < 0.01) and an increase in high density lipoprotein cholesterol (2.8%) after 12 weeks of treatment. No patient reported side effects and no clinically significant modifications in safety parameters were observed during the study. We conclude that fluvastatin sodium 40 mg once daily is efficacious, safe and well tolerated in the treatment of type IIA primary dyslipidemia.