Novel antidiabetic drugs in diabetic kidney disease accompanying type 2 diabetes : a minireview

Intensive hypoglycemic treatment is the strongest preventive strategy against the development of microvascular complications of type 2 diabetes (T2DM), including diabetic nephropathy. However, some antidiabetic drugs, i.e. sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have an additional renoprotective effect beyond glucose control by itself. Similar, both SGLT-2i and GLP1-RA have been demonstrated to decrease the risk of adverse cardiovascular (CV) events in CV outcome trials. Nevertheless, there are relevant differences in CV and renal effects of SGLT-2i and GLP1-RA. First, SGLT2i reduced the incidence and progression of albuminuria and prevented loss of kidney function, while predominant renal benefits of GLP1-RA were driven by albuminuria outcomes. Second, the risk of heart failure (HF) hospitalizations decreased on SGLT2i but not on GLP1-RA, which gives priority to SGLT2i in T2DM and HF, especially with depressed EF. Third, either GLP1-RA (reducing predominantly atherosclerosis-dependent events) or SGLT-2i, should be used in T2DM and established atherosclerotic CV disease (ASCVD) or other indicators of high CV risk. In this review, we have briefly compared clinical practice guidelines of the American Diabetes Association (2020 and 2021 versions), Polish Diabetes Association (2020) and the European Society of Cardiology/European Association for the Study of Diabetes (2019), with a focus on the choice between SGLT-2i and GLP1-RA in patients with diabetic kidney disease

Asymmetric dimethylarginine versus proton pump inhibitors usage in patients with stable coronary artery disease : a cross-sectional study

A recent experimental study suggested that proton pump inhibitors (PPI), widely used to prevent gastroduodenal complications of dual antiplatelet therapy, may increase the accumulation of the endogenous nitric oxide synthesis antagonist asymmetric dimethylarginine (ADMA), an adverse outcome predictor. Our aim was to assess the effect of PPI usage on circulating ADMA in coronary artery disease (CAD). Plasma ADMA levels were compared according to PPI use for ≥1 month prior to admission in 128 previously described non-diabetic men with stable CAD who were free of heart failure or other coexistent diseases. Patients on PPI tended to be older and with insignificantly lower estimated glomerular filtration rate (GFR). PPI use was not associated with any effect on plasma ADMA (0.51 ± 0.11 (SD) vs. 0.50 ± 0.10 µmol/L for those with PPI (n = 53) and without PPI (n = 75), respectively; p = 0.7). Additionally, plasma ADMA did not differ between PPI users and non-users stratified by a history of current smoking, CAD severity or extent. The adjustment for patients’ age and GFR did not substantially change the results. Thus, PPI usage does not appear to affect circulating ADMA in non-diabetic men with stable CAD. Whether novel mechanisms of adverse PPI effects on the vasculature can be translated into clinical conditions, requires further studies

Clinical correlates and prognostic value of plasma galectin-3 levels in degenerative aortic stenosis : a single-center prospective study of patients referred for invasive treatment

Galectin-3 (Gal-3), a β-galactoside-binding lectin, has been implicated in myocardial fibrosis, development of left ventricular (LV) dysfunction and transition from compensated LV hypertrophy to overt heart failure (HF), being a novel prognostic marker in HF. Risk stratification is crucial for the choice of the optimal therapy in degenerative aortic stenosis (AS), affecting elderly subjects with coexistent diseases. Our aim was to assess correlates and prognostic value of circulating Gal-3 in real-world patients with degenerative AS referred for invasive treatment. Gal-3 levels were measured at admission in 80 consecutive patients with symptomatic degenerative AS (mean age: 79 ± 8 years; aortic valve area (AVA) index: 0.4 ± 0.1 cm2/m2). The therapeutic strategy was chosen following a dedicated multidisciplinary team-oriented approach, including surgical valve replacement (n = 11), transcatheter valve implantation (n = 19), balloon aortic valvuloplasty (BAV) (n = 25) and optimal medical therapy (n = 25). Besides routine echocardiographic indices, valvulo-arterial impedance (Zva), an index of global LV afterload, was computed. There were 22 deaths over a median follow-up of 523 days. Baseline Gal-3 correlated negatively with estimated glomerular filtration rate (eGFR) (r = −0.61, p < 0.001) and was unrelated to age, symptomatic status, AVA index, LV ejection fraction, LV mass index or Zva. For the study group as a whole, Gal-3 tended to predict mortality (Gal-3 >17.8 vs. Gal-3 <17.8 ng/mL; hazard ratio (HR): 2.03 (95% confidence interval, 0.88–4.69), p = 0.09), which was abolished upon adjustment for eGFR (HR: 1.70 (0.61–4.73), p = 0.3). However, in post-BAV patients multivariate-adjusted pre-procedural Gal-3 was associated with worse survival (HR: 7.41 (1.52–36.1), p = 0.01) regardless of eGFR. In conclusion, the inverse eGFR–Gal-3 relationship underlies a weak association between Gal-3 and adverse outcome in patients with degenerative AS referred for invasive therapy irrespective of type of treatment employed. In contrast, pre-procedural Gal-3 appears an independent mortality predictor in high-risk AS patients undergoing BAV