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It is generally known that although a connection between abdominal obesity and chronic kidney disease (CKD) is well-established, there is a lack of systematic research investigating the specific roles of serum metabolites, including lipid metabolites, amino acid metabolites, carbohydrate metabolites and inflammatory substances in explaining this associations. We included 118,020 general patients with data of serum metabolites from UK Biobank. We defined abdominal obesity and CKD based on waist circumference and ICD-10 criteria. The serum metabolites were assessed by a high-throughput nuclear magnetic resonance (NMR) based metabolic biomarker profiling platform. We conducted mediation analysis by R software and used the proportion of mediation to quantify the mediation effect. This study demonstrated that lipid metabolites played a more important role in mediating the relationship between abdominal obesity and CKD than amino acid metabolites and carbohydrate metabolites. And Glycoprotein Acetyls (GlycA) was the strongest mediator for the correlation between abdominal obesity and CKD, accounting for 26.4 %. And In the mediation analysis stratified by sex, we found that the mediating effects of lipid metabolites were mostly higher in men than in women, while GlycA accounted for the largest proportion of the mediation association in both two groups (31.0 % for women and 19.8 % for men). Among lipid metabolites, amino acid metabolites, carbohydrate metabolites and inflammatory substances, our study showed that infammation marker GlycA was the novel and key mediator for the correlation between abdominal obesity and CKD. [ABSTRACT FROM AUTHOR]

The relationship between cereals intake and diabetes is unclear. We aimed to explore associations between individual cereals intake and risks of incident and progression of diabetes. We included 502,490 participants from UK Biobank at baseline. A single touchscreen food frequency questionnaire was used to estimate the intake of individual cereals (bran, biscuit, oat, muesli, and other cereals). Main outcomes included incident diabetes and diabetic complications of cardiovascular disease (CVD), chronic kidney disease (CKD) and diabetic retinopathy (DR). Polygenic risk score (PRS) of glycosylated hemoglobin (HbA1c) was calculated for mediating effects analysis. Among participants without diabetes, when compared to subjects who never had cereals, hazard ratios (95%CI) of developing diabetes in those who had ≥6 bowls/week were 0.72 (0.67–0.78) for bran, 0.86 (0.81–0.92) for biscuit, 0.75(0.66–0.84) for oat, and 0.57(0.53,0.61) for muesli. Among people with diabetes without CVD, a higher intake of aforementioned four individual cereals was associated with a 13%–32 % lower risk of developing CVD. Among people with diabetes without CKD, a higher intake of aforementioned four individual cereals was associated with a 9%–28 % lower risk of developing CKD. We observed a significant mediating effect of the PRS of HbA1c for the association between aforementioned four individual cereals and developing diabetes. A higher consumption of cereals was significantly associated with lower risks of diabetes and diabetic complications. Polygenic of HbA1c mediates the effect of cereals on incident diabetes. • Cereals intake is associated with lower risks of diabetes and its complications. HbA1c related genes mediate the effect of cereals on diabetes. [ABSTRACT FROM AUTHOR]

Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09–6.32] in EIMDS, and 4.31 [1.39–13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05–1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes. • Diabetic patients with RIA had a higher risk of CKD compared to normal aldosterone or renin-dependent aldosteronism. • Two-sample Mendelian randomization analysis indicated that RIA was causally associated with CKD in diabetic patients. • Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetic patients. [ABSTRACT FROM AUTHOR]