Mineralocorticoid Receptor Antagonist Improves Cardiac Structure in Type 2 Diabetes: Data From the MIRAD Trial.

OBJECTIVES: This study investigated the impact of the MR antagonist (MRA) eplerenone on LVM in type 2 diabetes patients at high risk for cardiovascular disease (CVD). BACKGROUND: MRA activation is associated with cardiac fibrosis and increased left ventricular mass (LVM), which is an independent predictor of adverse CVD, including heart failure in patients with type 2 diabetes. METHODS: A prespecified analysis of secondary endpoints in a randomized, double-blinded clinical trial of 140 patients with type 2 diabetes at high risk of or established CVD. Patients were randomized to receive high-dose eplerenone therapy (100 mg-200 mg) or placebo as an add-on to standard care for 26 weeks. Indexed LVM (LVMi) and T1 time were measured using cardiac magnetic resonance (CMR) imaging. Biomarkers included N-terminal pro-B-type natriuretic peptide (NT-proBNP), pro-collagen type I N-terminal propeptide (P1NP), and type III N-terminal propeptide (P3NP). RESULTS: Of 140 patients in the MIRAD trial, 104 patients were subject to CMR imaging (eplerenone: 54 patients; placebo: 50 patients). Mean LVMi at baseline was 74.2 ± 16 g/m2. The treatment effect (ie, between-group differences) was a decrease of 3.7 g/m2 following the eplerenone treatment (95% CI: -6.7 to -0.7; P = 0.017), with a corresponding decrease in absolute LVM. Plasma NT-proBNP concentrations decreased by 22% (P = 0.017) using eplerenone compared with placebo, and P1NP decreased 3.3 ng/mL (P = 0.019). No differences in T1 times or P3NP concentrations were observed between groups. CONCLUSIONS: The addition of high-dose eplerenone in high-risk type 2 diabetes was associated with a clear reduction in LVMi and in NT-proBNP and P1NP levels, which may suggest a clinical benefit in heart failure prevention. (EU Clinical trials: Mineralocorticoid Receptor Antagonists in Type 2 Diabetes [MIRAD]; 2015-002519-14).

Inulin and milk mineral fortification of a pork sausage exhibits distinct effects on the microbiome and biochemical activity in the gut of healthy rats.

This study investigated inulin and calcium-rich milk mineral incorporation into a pork sausage in order to examine the effects on microbiome and biochemical activity in the gastrointestinal tract upon ingestion. Rats (n = 48) were fed one of four sausages; a pork sausage enriched with 1) inulin (6.0%) and milk mineral (3%), 2) inulin (6.0%), 3) milk mineral (3%) or 4) control sausages without enrichment. NMR-based metabolomics revealed that inulin-enrichment increased the fecal concentration of short-chain fatty acids (SCFAs). Milk mineral-enrichment also increased SCFA concentrations, although less pronounced. In addition, milk mineral reduced the concentration of nitroso compounds in feces and small intestinal content. Combined enrichment with both inulin and milk mineral showed no cumulative effect on SCFA formation and seemed to oppose the milk mineral-induced reduction of nitroso compound formation. 16S rRNA gene amplicon sequencing indicated that alterations of the gut microbiome contributed to the observed effects.