Sodium-glucose cotransporter 2 inhibitors and heart failure decompensation: considerations on body composition and skeletal mass

: 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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Predictors of hospitalizations for heart failure decompensation in patients with comorbid occupational chronic obstructive pulmonary disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.0949 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

L.A Shpagina ◽

O.S Kotova ◽

I.S Shpagin ◽

G.V Kuznetsova ◽

N.V Kamneva ◽

...

Keyword(s):

Heart Failure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Chronic Obstructive ◽

Length Of Service ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Patients With Heart Failure ◽

Occupational Copd ◽

Heart Failure Decompensation

Abstract Background Heart failure decompensation requiring hospitalization is an important event, associated with mortality and investigating its predictors is topical problem. Chronic obstructive pulmonary disease (COPD) is a common comorbidity for heart failure. Both conditions share common molecular mechanisms such as systemic inflammation. COPD is heterogeneous and subpopulations with different inflammation patterns may interact with heart failure in different manner. Airway inflammation in occupational COPD may differs from COPD in tobacco smokers. Additionally cardiotoxicity of industrial chemicals influence heart failure features. Despite this biological plausibility, heart failure and occupational COPD comorbidity is not studied enough. Purpose To reveal predictors of hospitalizations for heart failure decompensation in patients with heart failure and occupational COPD comorbidity. Methods Occupational COPD patients (n=115) were investigated in a prospective cohort observational study. Comparison group – 115 tobacco smokers with COPD. Control group – 115 healthy persons. Controls were selected by propensity score matching, covariates were COPD duration, age and gender. Then COPD groups were stratified according to heart failure. Working conditions, echocardiography, spirometry, pulsoxymetry, 6-mitute walking test were done. Molecular markers of tissue damage – chemokine ligand 18 (CCL 18), lactate dehydrogenase, cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT pro-BNP), protein S100 beta, von Willebrand factor were measured in serum by ELISA. Follow up after initial assessment was 12 month. Predictors were determined by Cox proportional hazards regression with ROC analysis. Results Heart failure rate in occupational COPD patients were higher – 54.8% versus 36.5% in tobacco smokers with COPD, p<0.05. Heart failure with preserved ejection fraction was predominant – 40.9%. Prevalence of biventricular heart failure was 38.3%, isolated right heart failure – 13%, left heart failure – 2.6%. Cumulative hospitalization rate in occupational COPD with heart failure group was higher than in comparison group, 17.5% and 9.5% respectively, p=0.01. In Cox proportional hazards regression model predictors of hospitalizations for heart failure decompensation during 12 months in this group were length of service (HR 1.22, 95% CI: 1.03–2.5), aromatic hydrocarbons concentration at workplaces air (HR 1.4, 95% CI: 1.15–1.96), serum protein S100 beta (HR 1.10, 95% CI: 1.02–1.87), SaO2 (HR 1.2, 95% CI: 1.06–2.13). Area under the ROC curve was 0.82. Conclusion Length of service, aromatic hydrocarbons concentration at workplaces air, serum protein S100 beta, SaO2 are considered to be independent risk factors of heart failure decompensation required hospitalization in patients with heart failure and occupational COPD comorbidity. Funding Acknowledgement Type of funding source: None

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