Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study.

OBJECTIVES: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl-1/mIU∙l-1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). METHODS: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl-1/mIU∙l-1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. RESULTS: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. CONCLUSIONS: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl-1/mIU∙l-1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03224312).

The protective effect of teprenone in TNBS-induced ulcerative colitis rats by modulating the gut microbiota and reducing inflammatory response.

OBJECTIVE: Ulcerative colitis (UC), a chronic and refractory nonspecific inflammatory bowel disease, affects millions of patients worldwide and increases the risk of colorectal cancer. Teprenone is an acylic polyisoprenoid that exerts anti-inflammatory properties in rat models of peptic ulcer disease. This in vitro and in vivo study was designed to investigate the effects of teprenone on UC and to explore the underlying mechanisms. METHODS: Human intestinal epithelial cells (Caco-2 cells) serve as the in vitro experimental model. Lipopolysaccharide (LPS, 1 µg/mL) was employed to stimulate the production of pro-inflammatory cytokines (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α), Toll-like receptor-4 (TLR4), MyD88 expression, and NF-κB activation. A trinitrobenzene sulfonic acid (TNBS)-induced chronic UC rat model was employed for the in vivo assay. RESULTS: Pro-inflammatory cytokine stimulation by LPS in Caco-2 cells was inhibited by teprenone at 40 µg/mL through the TLR4/NF-κB signaling pathway. Teprenone attenuated TNBS-induced UC, decreased myeloperoxidase and malondialdehyde, induced TLR4 expression and NF-κB activation, and increased glutathione and zonula occludens-1 level in the rat colonic tissue. Moreover, Fusobacterium, Escherichia coli, Porphyromonas gingivalis elevation, and Mogibacterium timidum decline in UC rats were inhibited by teprenone. CONCLUSION: Based on our results, the protective effects of teprenone for UC may be related to its ability to modulate the gut microbiota and reduce the inflammatory response.

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). METHODS: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. RESULTS: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. CONCLUSIONS: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Association among calf circumference, physical performance, and depression in the elderly Chinese population: a cross-sectional study.

BACKGROUND: Depression and sarcopenia are common diseases in the elderly population. However, the association between them is controversial. Based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, a cross-sectional study was conducted to explore the relationship of calf circumference and physical performance with depression. METHODS: From the 8th wave of CLHLS conducted in 2018, data on calf circumference, physical performance, depressive symptoms, and demographic, socioeconomic, and health-related characteristics were collected. Multiple logistic regression was conducted to explore the impact of calf circumference, physical performance and their combination on depressive symptoms. RESULTS: We enrolled a total of 12,227 participants aged 83.4 ± 11.0 years, including 5689 (46.5%) men and 6538 (53.5%) women. Patients with depression were more likely to have low calf circumference (2274 [68.2%] vs. 5406 [60.8%], p<0.001) and poor physical performance (3[0, 6] vs. 1[0, 4], p<0.001). A significant multiplicative interaction was found between calf circumference and physical performance in their effect on depression. After adjusting for confounding factors, multiple logistic regression showed that a significant inverse correlation persisted between physical performance and depressive symptoms in normal (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.15-1.26, p<0.001) and low (OR = 1.14, 95% CI: 1.11-1.18, p<0.001) calf circumference group, while the association between calf circumference and depression disappeared. Participants with low calf circumference and poor physical performance were 2.21 times more likely to have depression than those with normal calf circumference and physical performance. All results were found to be robust in sensitivity analyses. CONCLUSIONS: Physical performance was significantly associated with depression in the elderly Chinese population. Attention should be paid to assess depressive symptoms in patients with poor physical performance.

Correlation analysis between foot deformity and diabetic foot with radiographic measurement.

Background: Foot deformity is a risk factor for diabetic foot ulcer. This study was aimed to investigate the relationship between hallux valgus (HV) and diabetic foot through the radiographic measurement. Methods: The patients with diabetic foot hospitalizing in the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University from September 2016 to June 2020 were selected. Then the foot plain X-ray radiographs were completed, and the size of HV angle (HVA) was measured. Their clinical data were collected, and the ulcer recurrence rate, amputation rate and mortality rate of the patients were followed up. Results: A total of 370 patients were included. According to HVA, patients were divided into non-HV group (HVA<15°), and mild (15°≤HVA ≤ 20°), moderate (20°40°) HV groups. The age, height, BMI, smoking history and glycosylated hemoglobin level among the non-HVA, mild, moderate, and severe HV group (P<0.05), while smoking history, HbA1c, eGFR and autonomic neuropathy were significantly lower in HV group than those in non-HV group (P<0.05). The ulcer area in patients with moderate HV was larger than that in non-HV patients, and the severity of infection in patients with severe HV was significantly higher than that the other three groups (P<0.05). Conclusion: The occurrence of HV is not only related to age and BMI, but also to the creatinine and eGFR level, autonomic neuropathy, lower limb arteriosclerosis occlusion, coronary heart disease and hypertension. Therefore, more attention should be paid to renal function screening, neuropathy screening and evaluation of lower extremity vascular lesions in patients with diabetes, especially those with moderate or higher HV.

Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Sarcopenia is an independent risk factor for all-cause mortality rate in patients with diabetic foot ulcers.

Objective: This study aimed to determine whether sarcopenia affects the all-cause mortality rate of patients with diabetic foot ulcers (DFUs). Research design and methods: The clinic-based observational study included 217 patients treated at the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University during a 4-year period. All subjects underwent dual-energy X-ray absorptiometry to determine their body composition during hospitalization. Diagnosis of sarcopenia was based on the Baumgartner diagnostic criteria. Patients were followed up regularly by phone calls until April 1, 2019, and their survival status was recorded.Univariate and multivariate Cox risk ratio regression models were used to analyze factors influencing the all-cause mortality rate of patients with DFUs. Results: Of the 217 patients, 158 people survived (82.7%), 33 died (17.3%), and 26 were lost to follow-up. The median follow-up time was 23 (Range 11-34) months. The majority of patients were male (68.6%), with a mean age of 67.29 ± 11.14 years. The 5-year survival rate was 68.3% and 45.9% for all study patients (n = 217) and sarcopenia patients (n = 81), respectively. Multivariate Cox risk regression model showed that age (HR 1.042[95%CI:1.006, 1.078], P = 0.021), sarcopenia (HR 5.051[95%CI:1.968, 12.961], P = 0.001), and serum creatinine (HR 1.007[95%CI: 1.003, 1.010], P < 0.001) were independent risk factors for all-cause mortality rate of patients with DFUs. Kaplan-Meier survival curve indicated that the survival rate of patients with sarcopenia was significantly lower than non-sarcopenia patients (P < 0.001). Conclusions: Sarcopenia is an independent risk factor for all-cause mortality of patients with DFUs and hence an important prognostic factor for patients with DFUs. Active prevention and improvement of sarcopenia can potentially improve the survival outcomes of this patient population.

Correlation Between Diabetic Peripheral Neuropathy and Sarcopenia in Patients with Type 2 Diabetes Mellitus and Diabetic Foot Disease: A Cross-Sectional Study.

PURPOSE: The present study was designed to determine the relationships between sarcopenia and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM) and diabetic foot disease (DFD) respectively. PATIENTS AND METHODS: A total of 1104 patients with T2DM and 257 patients with DFD were included in the study, which was designed as a cross-sectional study. Body composition was assessed using dual-energy X-ray-absorptiometry (DXA). The diagnosis of sarcopenia was based on the Baumgartner criteria. DPN was assessed by Neuropathy symptom score (NSS) and Neuropathy disability score (NDS), and the severity of neuropathy was divided into non-neuropathy symptom (NS), Mild NS, Moderate NS and Severe NS according to NSS. Logistic regression analyses were carried out to determine the relations of sarcopenia and DPN in patients with T2DM and NSS in patients with DFD, respectively. RESULTS: The prevalence of DPN was 80.0% in T2DM patients with sarcopenia and 70.3% in non-sarcopenia patients (P=0.007). Logistic regression analyses showed DPN was one of the independent risk factors for sarcopenia in T2DM patients (OR 1.564 [95% CI: 1.004, 2.435], P=0.048). The prevalence of DPN had no statistical significance in DFD patients with or without sarcopenia. However, the NSS of DFD patients with sarcopenia was higher than that of non-sarcopenia patients. In the multivariate logistic regression analysis, NSS was determined to be associated with sarcopenia in DFD patients (OR 1.387[95% CI: 1.074, 1.789], P=0.012). The appendicular lean mass (ALM) of DFD patients without NS was higher than patients with mild, moderate and severe NS (20.71±2.73 vs 16.57±3.62 vs 17.99±3.54 vs 17.23±3.29 Kg, P=0.028). CONCLUSION: DPN is an independent risk factor for sarcopenia in patients with T2DM and NSS is also independently correlated with sarcopenia in patients with DFD, with the latter being more obvious with the aggravation of neurological symptoms in DFD patients.