BaCKgRoUND aND aIMS: Indole is a microbiota metabolite that exerts anti-inflammatory responses. However, the relevance of indole to human non-alcoholic fatty liver disease (NAFLD) is not clear. It also remains largely unknown whether and how indole acts to protect against NAFLD. The present study sought to examine the association between the circulating levels of indole and liver fat content in human subjects and explore the mechanisms underlying indole actions in mice with diet-induced NAFLD. appRoaCH aND ReSUltS: In a cohort of 137 subjects, the circulating levels of indole were reversely correlated with body mass index. In addition, the circulating levels of indole in obese subjects were significantly lower than those in lean subjects and were accompanied with increased liver fat content. At the whole-animal level, treatment of high-fat diet (HFD)-fed C57BL/6J mice with indole caused significant decreases in the severity of hepatic steatosis and inflammation. In cultured cells, indole treatment stimulated the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a master regulatory gene of glycolysis, and suppressed macrophage proinflammatory activation in a PFKFB3-dependent manner. Moreover, myeloid cell-specific PFKFB3 disruption exacerbated the severity of HFD-induced hepatic steatosis and inflammation and blunted the effect of indole on alleviating diet-induced NAFLD phenotype. CoNClUSIoNS: Taken together, our results demonstrate that indole is relevant to human NAFLD and capable of alleviating diet-induced NAFLD phenotypes in mice in a myeloid cell PFKFB3-dependent manner. Therefore, indole mimetic and/or macrophage-specific PFKFB3 activation may be the viable preventive and/or therapeutic approaches for inflammation-associated diseases including NAFLD. (Hepatology 2020;72:1191-1203). N onalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and progresses to nonalcoholic steatohepatitis (NASH) when the liver displays overt inflammatory damage. (1,2) As the advanced form of NAFLD, NASH is one of the most common causes of liver

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The Chinese visceral adiposity index (CVAI) is a recently developed indicator of visceral adiposity. We investigated the predictive value of the CVAI for the development of dysglycemia (pre-diabetes and type 2 diabetes) and compared its predictive power with that of the Visceral adiposity index (VAI) and various anthropometric indices. This community-based study included 2,383 participants. We assessed the predictive power of adiposity indices by performing univariate and multivariate binary logistic regression analysis and calculating the area under the receiver-operating characteristic (ROC) curve according to their quartiles. Logistic regression analysis showed that individuals in higher CVAI quartiles at baseline were more likely to develop dysglycemia than those in lower CVAI quartiles. The area under the ROC curve for CVAI was significantly higher than that of other adiposity indices. In addition, among the various adiposity indices tested, the CVAI had the greatest Youden index for identifying dysglycemia in both genders. Our data demonstrate that the CVAI is a better predictor of type 2 diabetes and pre-diabetes than the VAI, BMI, waist circumference, waist-to-hip ratio and waist-to-height ratio in Chinese adults.

The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver-operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92-0.98) and 0.96 (95% CI, 0.92-0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver-operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65-0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84-0.95) and a specificity of 0.90 (95% CI, 0.83-0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78-0.91], =0.192; specificity: 0.92 [95% CI, 0.85-0.97],=0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended.

Background/Aims: Whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) could benefit patients with diabetes and albuminuria remains controversial. A systematic review and meta-analysis were conducted to answer this question by comparing ACE inhibitors or ARB with placebo among these patients. Methods: In this meta-analysis, electronic data sources (Medline, the Cochrane Collaboration, and EMBASE) were searched. Randomized controlled trials (RCTs) comparing ACE inhibitors or ARB with placebo in subjects with diabetes and albuminuria (defined as urinary albumin-to-creatinine ratio, UACR≥30mg/g Cr) were included. Outcomes parameters were all-cause mortality, end stage renal disease (ESRD), doubling of serum creatinine levels, and cardiovascular events (CV). Results: Twenty-six RCTs (including 20 for ACE inhibitors and 6 for ARB) were included, comprising 10378 participants with diabetes and albuminuria. Compared to placebo, treatment with ACE inhibitors or ARBs did not reduce all-cause mortality or CV. For renal outcomes, ARBs significantly reduced the risk of ESRD by 23% (odds ratio 0.77, 95%CI 0.65-0.92), while ACE inhibitors were not associated with a decreased risk of ESRD (0.69, 0.43-1.10). Both ACE inhibitors and ARBs reduced the risk of doubling of the serum creatinine level (0.60, 0.39-0.91 for ACE inhibitors; 0.75, 0.64-0.88 for ARBs), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results. Conclusion: In patients with diabetes and albuminuria, ARBs reduced risks of ESRD and doubling of the serum creatinine level. ACE inhibitors and ARBs failed to reduce all-cause mortality and CV. Based on the renoprotective effects, ARBs may be preferred for diabetic patients with albuminuria.

Context More than half of patients diagnosed with unilateral primary aldosteronism (UPA) suffer from persisting hypertension after unilateral adrenalectomy. Objective To develop and validate a nomogram-based preoperative score (NBPS) to predict clinical outcomes after unilateral adrenalectomy for UPA. Design and setting The NBPS was developed in an Asian cohort by incorporating predictors independently associated with remission of hypertension after unilateral adrenalectomy for UPA and validated in a Caucasian cohort. Participants Patients with UPA achieving complete biochemical success after unilateral adrenalectomy. Main outcome measure the predictive performance of NBPS compared with two previously developed outcome prediction scores: aldosteronoma resolution score (ARS) and primary aldosteronism surgical outcome (PASO) score. Results Ninety-seven of 150 (64.7%) patients achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165 (34.5%) in the validation cohort. A nomogram was established incorporating sex, duration of hypertension, aldosterone to renin ratio and target organ damage. The nomogram showed good concordance indices and calibration curves in both Asian and Caucasian cohorts. The area under the receiver operating characteristic curve (AUC) of NBPS for predicting hypertension remission in the training cohort was 0.853 (0.786-0.905), which was superior to ARS [0.745(0.667-0.812), p=0.019] and PASO score [0.747(0.670-0.815), p=0.012]. The AUC of NBPS in the validation cohort was 0.830 (0.764-0.884), which was higher than ARS [0.745 (95% CI 0.672-0.810), p=0.045], but not significantly different from PASO score [0.825 (95% CI 0.758-0.880), p=0.911]. Conclusion The NBPS is useful in predicting clinical outcome for UPA patients, especially in the Asian population.

Serum BPA may be a predictor of CKD progression in patients with primary hypertension.

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