SummaryThe macrobiotic, Ma-Pi 2 diet (12% protein, 18% fat and 70% carbohydrate), has shown benefit in adults with type 2 diabetes mellitus (T2DM). This pooled analysis aims to confirm results from four, 21-day intervention studies with the Ma-Pi 2 diet, carried out in Cuba, China, Ghana and Italy. Baseline and end of study biochemical, body composition and blood pressure data, were compared using multivariate statistical methods and assessment of the Cohen effect size (d). Results showed that all measured indicators demonstrated significant changes (p < 0.001); most of them with a very high (d ≥ 1.30), or high (d = 0.80-1.29) effect size. The global effect size of the diet was Italy (1.96), China (1.79), Cuba (1.38) and Ghana (0.98). The magnitude of the individual effect on each variable by country, and the global effect by country, was independent of the sample size (p > 0.05). Similarly, glycemia and glycemic profiles in all four studies were independent of the sample size (p = 0.237). The Ma-Pi diet 2 significantly reduced glycemia, serum lipids, uremia and cardiovascular risk in adults with T2DM. These results suggest that the Ma-Pi 2 diet could be a valid alternative treatment for patients with T2DM and point to the need for further clinical studies. Mechanisms related to its benefits as a functional diet are discussed.

OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to &lt;75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c &lt;7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c &lt;7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

Gal-1-treated chondrocytes was analyzed with RT-qPCR. Cell culture supernatants were subjected to ELISA for determination of MMP levels. For microarray analyses, RNA was isolated from chondrocytes cultured in absence or presence of Gal-1 (n ¼ 5). Bioinformatic analyses were performed using Gene Set Enrichment Analyses (GSEA) and subsequent NF-kB analyses were carried out using quantitative Western blot and RT-qPCR. Results: Immunohistochemical staining revealed increasing amounts of Gal-1-positive chondrocytes in regions of degenerated cartilage. Correlation analysis indicated a significant positive correlation between Gal-1 presence (% chondrocyte positivity) and cartilage degeneration (p<0.0001, Wilcoxon's signed rank test). In vitro, Gal-1 was secreted by chondrocytes, whereby this secretion was not inducible by proinflammatory cytokines. Binding of Gal-1 to chondrocyte surfaces and resulting effects were inhibitable by cognate sugar (lactose). Gal-1 treatment of chondrocytes increased the expression of matrix degrading enzymes (ADAMTS4, MMP1, MMP3, MMP13) and pro-inflammatory cytokines (IL1B, TNFA), while the expression of matrix components (AGC1, COL2A1) was decreased. In agreement, elevated secretion levels of pro-MMP-1, MMP-3 and pro-MMP-13 were detected. Analyses of the microarray data revealed an overexpression of chemokines and cytokines in Gal-1-treated chondrocytes. GSEA showed an overrepresentation of NF-kB DNA binding motifs in the promoters of most significantly induced genes prompting further investigation of the NF