El papel del riñón en la homeostasis de la glucosa y drogas de acción renal en el tratamiento de la diabetes mellitus tipo 2 / Kidney role in the glucose's homeostasis and drugs of renal action in the treatment of type 2 diabetes mellitus

Los riñones contribuyen a la homeostasis de la glucosa a través de varios mecanismos, incluyendo la gluconeogénesis, utilización y reabsorción de la glucosa a partir del filtrado glomerular. Bajo condiciones fisiológicas normales, la glucosa filtrada es casi totalmente reabsorbida en el epitelio de las células tubulares; en consecuencia, no aparece glucosa en la orina. El transporte de glucosa dentro de las células epiteliales del túbulo se cumple gracias a cotransportadores activos glucosa-sodio (SGLT), una familia de proteínas dependientes de adenosin trifosfato (ATP) involucradas en el transporte de glucosa contra un gradiente de concentración con carga simultánea de sodio, igualmente en contra gradiente. La mayoría de la glucosa filtrada es reabsorbida por medio del SGLT2, un transportador de baja afinidad pero elevada capacidad localizado, predominantemente, en el segmento S1 del tubo contorneado proximal. Por largo tiempo la inhibición del SGLT2 ha sido considerada como un abordaje terapéutico potencial de la hiperglucemia en la diabetes mellitus tipo 2 (DM2), ya que al prevenir la reabsorción de glucosa por los túbulos renales promueven su excreción renal y descienden los valores de la glucemia. Los datos en humanos indican que los inhibidores de SGLT2 representan una estrategia novedosa y efectiva para controlar las cifras de glucemia en los pacientes con DM2. El recién publicado estudio EMPA-REG OUTCOME diseñado para examinar los desenlaces cardiovasculares con empagliflozina en sujetos con DM2 y enfermedad ardiovascular coexistente mostró beneficios tempranos, los cuales se mantuvieron durante el período de observación(AU)

The kidneys contribute to glucose homeostasis through several mechanisms, including gluconeogenesis, glucose use, and glucose reabsorption from the glomerular filtrate. Under normal physiological conditions, this filtered glucose is almost completely reabsorbed by renal tubular epithelial cells; thus, there is no glucose in urine. The transport of glucose into renal tubular epithelial cells is mediated by active cotransporters, the SGLT, a family of ATP-dependent proteins involved in the transport of glucose against a concentration gradient with simultaneous transport of Na+ down a concentration gradient. Most of the filtered glucose is reabsorbed through SGLT2, a low-affinity high-capacity transporter located predominantly in the S1 segment of the renal proximal tubule. Inhibition of SGLT2 has long been regarded as a potential treatment approach for hyperglycemia during T2DM, as they prevent glucose reabsorption from renal tubules, thereby promoting urinary glucose excretion and decreasing plasma glucose levels. Current data in humans indicate that SGLT2 inhibitors represent an effective and novel strategy to control the plasma glucose concentration in patients with T2DM. The recently published EMPA-REG OUTCOME trial, which assessed cardiovascular outcomes with empagliflozin therapy in persons with type 2 diabetes mellitus and coexisting cardiovascular disease showed that the benefits were noted early and continued throughout the study(AU)

Time-weighted vs. conventional quantification of 24-h average systolic and diastolic ambulatory blood pressures.

BACKGROUND: Conventional calculation of mean 24-h ambulatory blood pressure (BP), SBP and DBP based on the average of all BP readings disregards the fact that a larger number of measurements is usually scheduled during the daytime than at night, an imbalance possibly leading to an overestimation of 24-h average BP. The aim of our study was to quantify this possible bias and to explore its determinants. METHODS: Four hundred and fifty untreated individuals were subdivided into three groups (150 individuals each) with three different ambulatory blood pressure measurement schedules for day/night: group I, four (day)/two (night) readings/h; group II, four (day)/three (night) readings/h; and group III, with BP readings every 30 min throughout 24 h. Hourly and 24-h averages were computed. The conventional 24-h averages of all SBP and DBP values were compared with the averages of hourly SBP and DBP mean values (time-weighted quantification). The difference between 24-h conventional and 24-h time-weighted BP was computed in each group and related to the degree of nocturnal BP dip and to the ratio between the number of readings of day and night. RESULT: In the three groups, 24-h conventional and 24-h time-weighted BP values were highly correlated (r > 0.99), 24-h conventional SBP and DBP being significantly higher (P < 0.01) than the corresponding 24-h time-weighted values in groups I and II but not in group III (Bland-Altman analysis). The bias magnitude was related to the day/night ratio in number of readings and to nocturnal BP dip in groups I and II (P < 0.01) but not in group III. CONCLUSION: The higher number of readings/h during daytime leads to an overestimation of conventional 24-h average BP, particularly in individuals with preserved nocturnal BP dipping. This can be avoided either by scheduling the same number of readings/h throughout 24 h or by performing a time-weighted quantification of 24-h BP. The clinical implications of these different approaches deserve further investigation.