A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes.

PURPOSE: Hypertension commonly co-exists with diabetes mellitus (DM), and both are closely related to adverse health outcomes. The activation of aldosterone and mineralocorticoid receptor (MR) may play important roles in this process. Therefore, we aim to evaluate the efficacy of MR antagonists on cardiovascular risk factors, including blood pressure (BP), glucose, lipids, renal function, fibrosis and inflammatory and its safety in patients with both hypertension and DM. METHODS: We searched PubMed, Embase, Web of Science and Cochrane databases for clinical trials published until December 31, 2019. Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included. Mean difference with 95% confidence intervals was used to report outcomes. RESULTS: Eleven randomised placebo-controlled trials with 640 participants were finally included with mean follow-up of 5 months. Compared to placebo, spironolactone significantly reduced office systolic (-6.57, 95%CI: -9.21, -3.93) and diastolic BP (-2.63, 95%CI: -4.25, -1.02) as well as ambulatory BP; increased glycosylated haemoglobin by 0.3 but no clear effect on fasting glucose. Spironolactone induced a significantly reduction of urinary albumin but increased serum creatinine (7.60, 95%CI: 4.94, 10.27) and decreased glomerular filtration rate (-4.28, 95%CI: -6.38, -2.18). Markers of fibrosis and inflammation, including NIIINP, PICP, hs-CRP and TNF-α were also decreased after spironolactone therapy. For lipid metabolism, there was no significant difference between groups. Spironolactone mildly increased serum potassium (0.30, 95%CI: 0.23, 0.37). 2.5% subjects treated with spironolactone experienced mild to moderate hyperkalaemia and received medication or dietary advice and another 1.6% developed severe hyperkalaemia and withdrawn from the studies. CONCLUSION: Spironolactone reduced BP and urinary albumin, improve fibrosis and inflammation, whereas slightly increases the glycosylated haemoglobin and serum creatinine in patients with hypertension and diabetes. Long-term RCTs to assess the effects of spironolactone on cardiovascular events in this population are warranted.

Does increased serum d-lactate mean subclinical hyperpermeability of intestinal barrier in middle-aged nonobese males with OSA?

Few attention has been directed to the potential effects of intermittent hypoxia experienced in obstructive sleep apnea on the integrity and permeability of intestinal barrier, particularly in adults. Therefore, we evaluated alteration in serum d-lactate concentration in middle-aged males with obstructive sleep apnea to value permeability of intestinal barrier. In this current cross-sectional study, consecutive 159 males were studied. Obstructive sleep apnea was determined by polysomnography and apnea hypopnea index ≥15 event/h was defined as obstructive sleep apnea. D-lactate, lipopolysaccharide binding protein, interleukin-1ß, interleukin-6 and tumor necrosis factor-α by ELISA method. Nonobese obstructive sleep apnea (OSA) males showed significantly higher serum d-LA than did nonobese [1374.35 (816-1735) µg/L vs 1166.43 (730-1815) µg/L, P = .018], and obese non-OSA ones [1374.35 (816-1735) µg/L vs 1188.75 (736-1557) µg/L, P = .045], whereas serum LBP levels showed no differences within groups. Serum IL-1ß was also slightly higher in nonobese OSA males, but with statistical significance, than in nonobese (19.39 ±â€Š4.67 ng/L vs 17.25 ±â€Š3.66 ng/L, P = .041), and obese non-OSA ones (19.39 ±â€Š4.67 ng/L vs 17.42 ±â€Š3.79 ng/L, P = .047), whereas other biomarkers, IL-6 and TNF-a did not show significant differences among groups. In stepwise multiple linear regression analysis, serum d-LA was independently positively associated with AHI (B = 5.577, P = .022), and ODI3 (B = 4.550, P = .024) and negatively with LSaO2 (B = -12.234, P = .019). Finally, we arrived at a conclusion that serum d-lactate was increased in nonobese middle-aged males with obstrutive sleep apnea, possibly suggesting existence of subclinical disruption of intestinal barrier, and showed significant associations with inflammatory mediators, possibly being involved in systemic inflammation of obstructive sleep apnea.