scholarly journals Multi-Organ Protective Effects of Sodium Glucose Cotransporter 2 Inhibitors

2021 ◽  
Vol 22 (9) ◽  
pp. 4416
Author(s):  
Hidekatsu Yanai ◽  
Mariko Hakoshima ◽  
Hiroki Adachi ◽  
Hisayuki Katsuyama
Keyword(s):  
Insulin Resistance ◽  
Hepatic Fibrosis ◽  
Tubuloglomerular Feedback ◽  
Liver Fat ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Organ Protection ◽  
Sodium Glucose Cotransporter ◽  
Outcome Trial ◽  
Hepatic Protection

Sodium glucose cotransporter 2 inhibitors (SGLT2i) block the reabsorption of glucose by inhibiting SGLT2, thus improving glucose control by promoting the renal excretion of glucose, without requiring insulin secretion. This pharmacological property of SGLT2i reduces body weight and improves insulin resistance in diabetic patients. Such beneficial metabolic changes caused by SGLT2i are expected to be useful not only for glucose metabolism, but also for the protection for various organs. Recent randomized controlled trials (RCTs) on cardiovascular diseases (EMPA-REG OUTCOME trial and CANVAS program) showed that SGLT2i prevented cardiovascular death and the development of heart failure. RCTs on renal events (EMPA-REG OUTCOME trial, CANVAS program, and CREDENCE trial) showed that SGLT2i suppressed the progression of kidney disease. Furthermore, SGLT2i effectively lowered the liver fat content, and our study demonstrated that SGLT2i reduced the degree of hepatic fibrosis in patients at high-risk of hepatic fibrosis. Such promising properties of SGLT2i for cardiovascular, renal, and hepatic protection provide us the chance to think about the underlying mechanisms for SGLT2i-induced improvement of multiple organs. SGLT2i have various mechanisms for organ protection beyond glucose-lowering effects, such as an increase in fatty acids utilization for hepatic protection, osmotic diuresis for cardiac protection, an improvement of insulin resistance for anti-atherogenesis, and an improvement of tubuloglomerular feedback for renal protection.

scholarly journals Insulin resistance in non-diabetic patients with chronic hepatitis C: what does it mean?

2011 ◽  
Vol 55 (6) ◽  
pp. 412-418 ◽  
Author(s):  
Aécio Flávio Meirelles de Souza ◽  
Fábio Heleno de Lima Pace ◽  
Júlio Maria Fonseca Chebli ◽  
Lincoln Eduardo Villela Vieira de Castro Ferreira
Keyword(s):  
Insulin Resistance ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Hepatic Fibrosis ◽  
Liver Steatosis ◽  
Diabetic Patients ◽  
Histological Findings ◽  
C Reactive Protein ◽  
Reactive Protein

OBJECTIVES: To determine the prevalence of insulin resistance (IR) in non-diabetic patients with chronic hepatitis C, and to assess the association between IR, laboratory parameters and histological findings. SUBJECTS AND METHODS: Eighty-two patients had their serum analyzed for glucose, lipid profile, C-reactive protein (CRP), ferritin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HOMA-IR, viral load and HCV genotype. Patients with HOMA-IR levels > 2.5 were considered as carriers of insulin resistance. RESULTS: IR was observed in 27% of patients and was associated with age, waist circumference and body mass index. IR patients were more likely to have more advanced hepatic fibrosis and necroinflammatory activity, higher levels of aminotransferases and liver steatosis than patients without IR. CONCLUSIONS: Insulin resistance is often present in patients with chronic hepatitis C, and this parameter is associated with more advanced HCV-related hepatic fibrosis.

scholarly journals Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease

Hypertension ◽  
2021 ◽  
Author(s):  
Guanghong Jia ◽  
James R. Sowers
Keyword(s):  
Insulin Resistance ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Epidemiological Studies ◽  
Diabetic Patients ◽  
Epithelial Sodium Channels ◽  
Mitochondria Dysfunction ◽  
Blood Pressure Targets ◽  
Sodium Glucose Cotransporter ◽  
Underlying Mechanisms

Epidemiological studies have documented that insulin resistance and diabetes not only constitute metabolic abnormalities but also predispose to hypertension, vascular stiffness, and associated cardiovascular disease. Meanwhile, excessive arterial stiffness and impaired vasorelaxation, in turn, contribute to worsening insulin resistance and the development of diabetes. Molecular mechanisms promoting hypertension in diabetes include inappropriate activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, mitochondria dysfunction, excessive oxidative stress, and systemic inflammation. This review highlights recent studies which have uncovered new underlying mechanisms for the increased propensity for the development of hypertension in association with diabetes. These include enhanced activation of epithelial sodium channels, alterations in extracellular vesicles and their microRNAs, abnormal gut microbiota, and increased renal sodium-glucose cotransporter activity, which collectively predispose to hypertension in association with diabetes. This review also covers socioeconomic factors and currently recommended blood pressure targets and related treatment strategies in diabetic patients with hypertension.

scholarly journals Cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors in diabetic and nondiabetic patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Boyang Xiang ◽  
Xiaoya Zhao ◽  
Xiang Zhou
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Large Scale ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Sodium Glucose Cotransporter ◽  
Outcome Trial

AbstractSodium-glucose cotransporter 2 inhibitors (SGLT2i) were developed as antidiabetic agents, but accumulating evidence has shown their beneficial effects on the cardiovascular system. Analyses of the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) suggested that these benefits are independent of glycemic control. Several large-scale outcome trials of SGLT2i also showed cardiovascular benefits in nondiabetic patients, strengthening this perspective. Extensive animal and clinical studies have likewise shown that mechanisms other than the antihyperglycemic effect underlie the cardiovascular benefits. Recent clinical guidelines recommend the use of SGLT2i in patients with type 2 diabetes mellitus and cardiovascular diseases because of the proven cardiovascular protective effects. Since the cardiovascular benefits are independent of glycemic control, the therapeutic spectrum of SGLT2i will likely be extended to nondiabetic patients.

scholarly journals Antihyperglycemic agents as novel natriuretic therapies in diabetic kidney disease

2018 ◽  
Vol 315 (5) ◽  
pp. F1406-F1415 ◽  
Author(s):  
David León Jiménez ◽  
David Z. I. Cherney ◽  
Petter Bjornstad ◽  
Luis Castilla-Guerra ◽  
José Pablo Miramontes González
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Kidney Disease ◽  
Sglt2 Inhibitors ◽  
Tubuloglomerular Feedback ◽  
Protective Effects ◽  
Sodium Glucose Cotransporter ◽  
Sglt2 Inhibition ◽  
Clinical Benefits ◽  
Intraglomerular Pressure

While sodium-glucose cotransporter-2 (SGLT2) inhibitors have been used for the routine management of type 2 diabetes for several years, it is perhaps their natriuretic effects that are most important clinically. This natriuresis activates tubuloglomerular feedback, resulting in reduced glomerular hypertension and proteinuria, leading to renal protective effects in the EMPA-REG OUTCOME and CANVAS Program trials. In the cardiovascular system, it is likely that plasma volume contraction due to natriuresis in response to SGLT2 inhibition is at least in part responsible for the reduction in the risk of heart failure observed in these trials. We compare this mechanism of action with other antidiabetics. Importantly, other diuretic classes, including thiazide and loop diuretics, have not resulted in such robust clinical benefits in patients with type 2 diabetes, possibly because these older agents do not influence intraglomerular pressure directly. In contrast, SGLT2 inhibitors do have important physiological similarities with carbonic anhydrase inhibitors, which also act proximally, and have been shown to activate tubuloglomerular feedback.

Relation of insulin resistance and left ventricular function and structure in non-diabetic patients with essential hypertension

2005 ◽  
Vol 60 (2) ◽  
pp. 191-198 ◽  
Author(s):  
Harun EVRENGUL ◽  
Dursun DURSUNOGLU ◽  
Asuman KAFTAN ◽  
Fethi KILICASLAN ◽  
Halil TANRIVERDI ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Essential Hypertension ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Diabetic Patients

SGLT-2 Inhibition: Novel Therapeutics for Reno-and Cardioprotection in Diabetes Mellitus

2019 ◽  
Vol 15 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Angus Gill ◽  
Stephen P. Gray ◽  
Karin A. Jandeleit-Dahm ◽  
Anna M.D. Watson
Keyword(s):  
Sympathetic Nerve Activity ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Preclinical Research ◽  
Type 2 Diabetic Patients ◽  
Nerve Activity ◽  
Current State ◽  
Glucose Reabsorption ◽  
Type 2 Diabetic

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.

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