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Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment

2019-09-12 02:34:41 | BioPortfolio

Summary

The purpose of this study is to investigate the effects of Dapagliflozin (FORXIGA) 10mg (n=20) versus placebo (n=20) administered orally, daily, in addition to current therapy, on the renal concentration mechanism, the mobilization skin and muscle Na+ stores, and the mobilization of muscle and liver fat stores in diabetic patients with heart failure New York Heart Association (NYHA) classes I and II, in a 4-week randomized, double-blind, placebo-controlled trial.

Description

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors improve cardiovascular outcomes with unprecedented reductions in cardiovascular mortality, renal disease progression, and heart failure hospitalizations, but the underlying mechanisms of these beneficial effects are unclear. The investigators hypothesize that the actions are not solely related to Na+ elimination and volume-related blood pressure reduction. Our previous work has shown that increased Na+ excretion leads to profound metabolic changes and energy utilization in the body in order to avoid water loss and dehydration. Our hypothesis is that dapagliflozin treatment induces high renal Na+ and glucose excretion predisposing to water loss, to which the body responds by concentrating the osmolytes into the urine, in an effort to prevent dehydration. Increased urea accumulation in the renal medulla, necessary to provide the osmotic driving force for water reabsorption, requires increased hepatic urea production, which is a costly, energy-intense process. This metabolic response leads to a reprioritization of energy metabolism in favour of amino-acid utilization in the liver, and a switch in fuel utilization in favour of fatty acids in the skeletal muscle.

Study Design

Conditions

Diabetes Mellitus

Intervention

Dapagliflozin 10 MG [Farxiga]

Location

National Heart Centre Singapore
Singapore
Singapore
169609

Status

Recruiting

Source

National Heart Centre Singapore

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-09-12T02:34:41-0400

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Medical and Biotech [MESH] Definitions

A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.

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A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.

A strain of Rattus norvegicus which is a model for spontaneous insulin-dependent diabetes mellitus (DIABETES MELLITUS, INSULIN-DEPENDENT).

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