scholarly journals Effects of sodium-glucose cotransporter 2 inhibitor, tofogliflozin, on the indices of renal tubular function in patients with type 2 diabetes

2018 ◽  
Vol 1 (2) ◽  
pp. e00015 ◽  
Author(s):  
Kiyohide Nunoi ◽  
Yuichi Sato ◽  
Kohei Kaku ◽  
Akihiro Yoshida ◽  
Hideki Suganami
Keyword(s):  
Type 2 Diabetes ◽  
Tubular Function ◽  
Renal Tubular Function ◽  
Sodium Glucose Cotransporter ◽  
Renal Tubular

scholarly journals Sodium-glucose cotransporter-2 inhibitors: updated evidence on their efficacy and safety in patients with type-2 diabetes

2020 ◽  
Vol 9 (4) ◽  
pp. 666
Author(s):  
Vipul Gupta ◽  
Girish Khurana
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Initial Therapy ◽  
Sodium Glucose Cotransporter ◽  
Lower Glucose ◽  
Glucose Reabsorption ◽  
Metabolic Aspect ◽  
Treatment Of Diabetes ◽  
Renal Tubular

Management of type-2 diabetes mellitus (T2DM) is challenging. The scope of existing therapies toward T2DM has transformed remarkably. These large assortments of therapies have produced evidence-based data. Sodium-glucose cotransporter-2 inhibitor (SGLT-2i) is the most recent class of oral anti-hyperglycemic agents. They are approved by Food and Drug Administration for the treatment of diabetes mellitus. SGLT-2i has a unique mechanism of action and that lower glucose independent of insulin. They reduce renal tubular glucose reabsorption, thereby lowering blood glucose without stimulating the release of insulin. Additional advantages involve suitable effects on blood pressure and weight. According to guidelines of the American Association of Clinical Endocrinologists/ the American College of Endocrinology 2016, SGLT-2i (in the form of canagliflozin, dapagliflozin, and empagliflozin) is one of the acceptable alternatives to metformin as initial therapy towards T2DM. Canagliflozin, dapagliflozin, and empagliflozin reduce the cardiovascular risk in comparison to placebo as the part of standard care. This review article focuses on the clinical trials published over the past year and specifically the metabolic aspect of SGLT-2i and the adverse effects related to SGLT-2 inhibitors. 

scholarly journals Renal functional reserve and tubular function in patents with type 2 diabetes mellitus

2011 ◽  
Vol 14 (2) ◽  
pp. 82-85
Author(s):  
Dilyara Makhmutrievna Khakimova ◽  
Adelya Nailevna Maksudova ◽  
Il'dar Gazimdzhanovich Salikhov
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Tubular Function ◽  
Tubular Dysfunction ◽  
Partial Functions ◽  
Functional Reserve ◽  
Renal Functional Reserve ◽  
Renal Tubular

Aim. To study renal functional reserve and partial functions in patents with type 2 diabetes mellitus in the absence of renal lesionsMaterials and methods. We examined 42 patients (17 men and 24 women) aged 38-69 (mean 49.8?8.3) years with DM2 4.6?2.6 yr in duration.Control group comprised 32 practically healthy subjects. Intrarenal hemodynamics was estimated from RFR values. Ethanolamine, uric acid, Ca,and P levels were measured in sera and 24-hr urine; daily excretion of ammonia and aminonitrogen in the urine was determined. Results. The patients were divided into 2 groups based on the results of RFR measurement. FRF remained unaltered in 21 patients (mean 60.7?27.6%)and decreased in the absence of filtration reserve in 20 (-25.8?23.4%). Correlation analysis revealed the relationship of lipid metabolism and abdominalobesity with the renal tubular function and intraglomerular hemodynamics. Conclusion. Examination of DM2 patients without clinical and laboratory signs of renal lesions revealed compromised function of all nephron compartments,viz. intraglomerular hypertension, impaired stability of renal cell membranes, and tubular dysfunction. The latter is related to hemodynamic disturbances.

P1008THERAPY WITH SODIUM-GLUCOSE COTRANSPORTER TYPE 2 INHIBITORS INCREASES KLOTHO IN TYPE 2 DIABETIC PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Juan Navarro-González ◽  
Carla Ferri ◽  
Ernesto Martín-Núñez ◽  
Javier Donate-Correa ◽  
Nayra Pérez-Delgado ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Urinary Excretion ◽  
Mrna Expression ◽  
Expression Levels ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Sodium Glucose Cotransporter ◽  
Renal Tubular ◽  
Mrna Expression Levels

Abstract Background and Aims Klotho (KL) is a transmembrane protein that is expressed the highest in the tubular cells of the kidneys. In addition to membrane KL, a secreted form of this protein that is present in blood and urine is generated by ectodomain shedding of membrane KL from the cell surface or from the KL gene through alternative splicing. Preserved KL expression has been related to physiological protection in the human kidneys. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new class of antidiabetic drugs with important renal benefits. The aim of the present proof-of-concept study was to analyze if treatment with SGLT2i is associated with changes in soluble KL concentrations as well as with modifications in mRNA expression levels of the KL gene in renal tubular cells. Method Thirty-four patients (18 males and 16 males; mean age 61±5 years) with type 2 diabetes (mean diabetes time higher than 10 years) and CKD G2-A2, all treated with metformin and blockers of the renin-angiotensin system during more than one year, were included in the study. Twenty-four of them received SGLT2i during 6 months (8 empagliflozin, 8 canagliflozin, 8 dapagliflozin), and their data and evolution were compared with a group of 10 patients matched by age, sex and stage of CKD who received sulfonylureas or DPP4 inhibitors. Serum and urine levels of soluble KL and tumor necrosis factor-alpha (TNFa) were determined by ELISA. In addition, the effect of SGLT2i on mRNA expression levels of KL was assessed in vitro in renal tubular cells cultures. Results Baseline median values of serum and urinary KL and TNFa were similar in both groups. Urinary KL was inversely correlated with albuminuria and TNFa excretion (r = -0.39 and r = -0.37, respectively, P<0.05). There were no relationship between the serum and urinary levels of these molecules, suggesting their renal origin. At the end of the study, there was a similar improvement in metabolic control, with a reduction in blood pressure significantly higher in patients treated with SGLT2i. Estimated glomerular filtration rate and albuminuria decreased by 5.8% and 17%, respectively, in subjects receiving SGLT2i (P<0.0001), without changes in the control group. In patients under SGLT2i therapy there was a 21% significant reduction in urinary TNFa with a concomitant 41% increase in urinary KL (P<0.001); there was also a small but significant rise in serum KL (P<0.01 vs baseline). Partial correlation analysis showed that the changes in the urinary excretion of albumin and TNFa were associated with the variation in urinary KL after controlling for other variables (r = -0.50, P<0.01, and r = -0.41, P<0.05, respectively). Finally, renal tubular cells cultured with dapagliflozin showed a significant and dose-dependent increase of mRNA expression levels of KL. Conclusion Treatment with SGLT2i induces a reduction in albuminuria and modulates inflammation (as reflected by a decrease in the urinary excretion of TNFa), which is associated with a significant increase in soluble KL concentrations as well as mRNA expression levels of the KL gene. The preservation of KL by SGLT2i may be an important mechanism of renal protection in type 2 diabetes.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

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