Glucose homeostasis is orchestrated through the integrated actions of pancreatic insulin secretion, hepatic glucose production, and peripheral glucose utilization. However, the mechanism governing gut glucose metabolism remains incompletely characterized. We employed positron emission tomography coupled with metabolomic profiling to demonstrate that the rodent small intestine possesses a remarkable capacity to sequester and catabolize circulating fasting glucose. Notably, these effects were consistent across sexes and various physiological conditions. Mechanistic studies revealed that gut glucose assimilation during fasting is mediated by basolateral GLUT1, which is modulated through reciprocal regulation by apical angiotensin-converting enzyme 2 (ACE2) and the neutral amino acid transporter SLC6A19. Impaired gut glucose assimilation contributes to hyperglycemia in both rodent models and type 2 diabetic patients, which is associated with inhibition of SLC6A19 and disruption of ACE2/GLUT1 interaction yet ameliorated by SGLT2 inhibitors. We highlight that the small intestine harnesses glucose homeostasis through reciprocal interactions between glucose and amino acid transporters.

Background:Microcirculation dysfunction commonly occurs in patients with hypertension and diabetes. We aimed to evaluate the changes in sublingual microcirculation among patients with primary aldosteronism (PA), subclinical primary aldosteronism (sPA), essential hypertension (EH), and healthy individuals and aimed to use sublingual microcirculation to screen for PA. Methods:From January 2023 to January 2024, we consecutively enrolled 191 hypertensive patients (89 EH patients, 51 sPA patients, and 51 PA patients) and 44 healthy individuals. Sublingual microcirculatory images were captured via side-stream dark-field (SDF) microcirculation microscopy, and total and perfused vessel density (TVD and PVD) were calculated. Patient demographic and laboratory data as well as factors influencing microcirculation parameters were assessed. Results:Compared with healthy individuals (TVD: 13.97 ± 0.62 mm/mm2; PVD: 11.46 ± 0.53 mm/mm2), EH (12.24 ± 0.56; 9.92 ± 0.34), sPA (11.49 ± 0.51; 9.46 ± 0.33) and PA (10.91 ± 0.68; 8.85 ± 0.43) patients exhibited significant microcirculation dysfunction (TVD and PVD). Receiver operating characteristic (ROC) curve analysis revealed that both TVD and the PVD could effectively mirror microcirculation abnormalities in PA patients. We derived a combined evaluation index (CEI) that was composed of the TVD and the PVD for screening PA. By plotting the receiver operating characteristic (ROC) curve, the CEI (AUC: 0.9818 [0.9660, 0.9977]) demonstrated a superior screening effect for PA compared with the aldosterone-to-renin ratio (ARR, AUC: 0.9505 [0.9194, 0.9817]). Conclusions:Patients with PA had marked microcirculatory dysfunction, which was strongly associated with the ARR. Sublingual microcirculation might be a noninvasive method for the early detection of primary aldosteronism in hypertensive patients.

Primary aldosteronism (PA) is susceptible to cardiovascular and renal damage. However, the role of dietary salt intake in aldosterone-related target organ damage (TOD) in PA remains elusive. This study aimed to investigate whether high salt intake enhances the effect of aldosterone on TOD in PA patients. A total of 361 patients with PA and 102 patients with essential hypertension (EH) were enrolled in this study. All participants underwent tests for the aldosterone/renin ratio, 24-hour urinary sodium, biochemical examination, and TOD assessment via echocardiography, carotid ultrasound, and urine microalbumin measurements. Patients were categorized on the basis of salt intake and aldosterone levels. Compared with the control group, PA patients with high salt intake presented an increased urinary albumin-to-creatinine ratio (UACR), a more significant effect of aldosterone on blood pressure, and remarkable cardiac hypertrophy and renal damage (p < 0.05). Quintile-based regression analysis revealed that the odds ratio between the highest quintile of the plasma aldosterone level and the UACR was twice that of the lowest quintile. In the adjustment models, the relationships between aldosterone and the left ventricular mass index (LVMI) were not statistically significant. Linear correlation analysis further revealed that high salt intake could reinforce the correlation between aldosterone and creatinine, log-UACR and LVMI in PA patients, but this effect was not observed in EH patients. This study suggests that high salt intake can exacerbate aldosterone-related renal impairment, while it is crucial in aldosterone-related cardiac damage in PA patients.

Ectopic ACTH secretion-related Cushing's syndrome may manifest as a rapid onset of hypercortisolism, elevated urinary free cortisol (UFC) and blood ACTH concentrations, and hypokalemia. However, for patients whose primary lesions are difficult to remove, bilateral adrenalectomy is the recommended treatment method according to guidelines. Here, we present a case of non-small cell lung cancer with metastasis. Due to significant deconditioning, the patient was unable to undergo bilateral adrenalectomy and instead underwent catheter-based adrenal ablation; subsequently, he achieved clinical remission and completed the first phase of chemotherapy.

Although epidemiological studies have established a link between diabetes and frailty, the dynamic changes in frailty before and after diabetes diagnosis remained inadequately characterized. This study aimed to examine the trajectories of frailty preceding and following diabetes diagnosis in older adults and to identify potential modifiers of the association between diabetes and trajectories of frailty. We included adults aged≥65 years without baseline diabetes from the Chinese Longitudinal Healthy Longevity Survey (2002–2018). Incident diabetes was defined by self-reported physician diagnosis or diabetes-related hospitalization. The date of diagnosis was estimated as the midpoint between the last non-diabetic interview and the first report of diabetes. Frailty was assessed repeatedly using a 43-item frailty index (FI). Linear mixed-effects models were used to compare frailty trajectories before and after diabetes onset. Among 9,992 participants (mean age 82.12 years; 51.31

Roux-en-Y gastric bypass (RYGB) results in glucose-lowering in patients with type 2 diabetes mellitus (T2DM) and may be associated with increased intestinal glucose excretion. However, the contribution of intestinal glucose excretion to glycemic control after RYGB and its underlying mechanisms are not fully elucidated. Here, we confirmed that intestinal glucose excretion significantly increased in obese rats after RYGB, which was negatively correlated with postoperative blood glucose levels. Moreover, we also found that the contribution of Biliopancreatic limb length, an important factor affecting glycemic control after RYGB, to the improvement of glucose metabolism after RYGB attributed to the enhancement of intestinal glucose excretion. Subsequently, we further determined through multiple animal models that intestinal glucose excretion is physiological rather than pathological and plays a crucial role in maintaining glucose homeostasis in the body. Finally, we employed germ-free mice colonized with fecal samples from patients and rats to demonstrate that enhanced intestinal glucose excretion after RYGB is directly modulated by the surgery-induced changes in the gut microbiota. These results indicated that the gut microbiota plays a direct causal role in the hypoglycemic effect of RYGB by promoting intestinal glucose excretion, which may provide new insights for developing gut microbiota-based therapies for T2DM.

OBJECTIVES:A large number of patients with non-obese non-alcoholic fatty liver disease (NAFLD) in China remain undiagnosed and untreated due to insufficient awareness and ineffective pharmacotherapy. Therefore, a convenient, predictive marker and diagnostic tools are imperative. This study aimed to investigate the ability of the triglyceride glucose index (TyG) in predicting non-obese NAFLD. DESIGN:An observational cross-sectional study. SETTING:Department of Health Management, large urban academic medical centre and DRYAD database data. PARTICIPANTS:This study included 456 patients with non-obese NAFLD and matched 456 non-fatty liver controls according to age, sex and body mass index (BMI). PRIMARY AND SECONDARY OUTCOME MEASURES:The receiver operating characteristic (ROC) curve was used to evaluate the predictive role of the TyG index in non-obese NAFLD. Based on the TyG index, a clinical prediction model for non-obese NAFLD was constructed, then the prediction model was verified by the DRYAD database (n=11 562). RESULTS:TyG in non-obese NAFLD was higher than that in controls (9.00 (8.66-9.40) vs 8.46 (8.10-8.83), p<0.001). Logistic regression analysis showed that TyG was an independent risk factor for non-obese NAFLD (OR=9.03, 95% CI: 5.46 to 14.94, p<0.001). ROC analysis showed that the area under the curve (AUC) was 0.78, the sensitivity was 82.5%, the specificity was 60.5%. Based on the TyG index, sex, age and BMI, the AUC of the predictive model for non-obese NAFLD was 0.78 (95% CI: 0.75 to 0.81, p<0.001). Using the DRYAD database to verify the prediction model, the AUC of the verification group was 0.85 (95% CI: 0.84 to 0.86, p<0.001). CONCLUSIONS:The high level of the TyG may be an independent risk factor for non-obese NAFLD. The prediction model for non-obese NAFLD based on the TyG index has good clinical prediction value.

BACKGROUND Percutaneous adrenal ablation (PAA) is an effective and safe therapy for treating patients with primary aldosteronism (PA). However, its effectiveness in comparison to that of adrenalectomy (ADX) and mineralocorticoid receptor antagonists (MRAs) remains unclear.METHODS Databases were searched including PubMed, Embase, and The Cochrane Library. Studies included patients with PA who received two of three different treatments (ADX, MRAs, or PAA) and reported our interested outcomes, including blood pressure, serum potassium, and the aldosterone-to-renin ratio (ARR).RESULTS In a total of 10,681 patients from 47 studies were identified. Both ADX and PAA showed superior clinical success (systolic blood pressure (BP): ADX: -4.69 (-6.4, -2.95), PAA: -3.96 (-9.05, 0.99); diastolic BP: ADX: -3.14 (-4.55, -1.85), PAA: -2.99 (-6.96, 0.98)) compared with MRAs. According to the Bayesian ranking curves (surface under the cumulative ranking values), ADX ranked first for all outcomes of interest (systolic BP: 81.02%, diastolic BP: 76.95%, serum potassium: 96.55%, and ARR: 88.03%), while PAA ranked second for all outcomes (systolic BP: 65.94%, diastolic BP: 69.66%, serum potassium: 50%, and ARR: 45.14%).CONCLUSIONS The findings of this network meta-analysis suggest that PAA could be an alternative treatment for patients with PA who are unable to opt for surgery or MRA therapy, and its clinical and biochemical success falls between those of ADX and MRAs.

Background: Obesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms. Methods: The C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating adiponectin secretion. Results: Apigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased adiponectin secretion from BAT; knockdown of adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression. Conclusions: Our study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased adiponectin levels by inhibiting CD38.

IntroductionExcess salt intake is not only an independent risk factor for heart failure, but also one of the most important dietary factors associated with cardiovascular disease worldwide. Metabolic reprogramming in cardiomyocytes is an early event provoking cardiac hypertrophy that leads to subsequent cardiovascular events upon high salt loading. Although SGLT2 inhibitors, such as canagliflozin, displayed impressive cardiovascular health benefits, whether SGLT2 inhibitors protect against cardiac hypertrophy-related metabolic reprogramming upon salt loading remain elusiveObjectivesTo investigate whether canagliflozin can improve salt-induced cardiac hypertrophy and the underlying mechanisms.MethodsDahl salt-sensitive rats developed cardiac hypertrophy by feeding them an 8% high-salt diet, and some rats were treated with canagliflozin. Cardiac function and structure as well as mitochondrial function were examined. Cardiac proteomics, targeted metabolomics and SIRT3 cardiac-specific knockout mice were used to uncover the underlying mechanisms.ResultsIn Dahl salt-sensitive rats, canagliflozin showed a potent therapeutic effect on salt-induced cardiac hypertrophy, accompanied by lowered glucose uptake, reduced accumulation of glycolytic end-products and improved cardiac mitochondrial function, which was associated with the recovery of cardiac expression of SIRT3, a key mitochondrial metabolic regulator. Cardiac-specific knockout of SIRT3 not only exacerbated salt-induced cardiac hypertrophy but also abolished the therapeutic effect of canagliflozin. Mechanistically, high salt intake repressed cardiac SIRT3 expression through a calcium-dependent epigenetic modifications, which could be blocked by canagliflozin by inhibiting SGLT1-mediated calcium uptake. SIRT3 improved myocardial metabolic reprogramming by deacetylating MPC1 in cardiomyocytes exposed to pro-hypertrophic stimuli. Similar to canagliflozin, the SIRT3 activator honokiol also exerted therapeutic effects on cardiac hypertrophy.ConclusionCardiac mitochondrial dysfunction caused by SIRT3 repression is a critical promotional determinant of metabolic pattern switching underlying salt-induced cardiac hypertrophy. Improving SIRT3-mediated mitochondrial function by SGLT2 inhibitors-mediated calcium handling would represent a therapeutic strategy against salt-related cardiovascular events.

Background Roux-en-Y gastric bypass (RYGB) surgery is an effective metabolic surgery against diabetes and obesity. Clinical evidence indicates that patients with severe obesity have a poor curative effect in losing weight if they suffer from leptin or its receptor deficiency, but the underlying mechanism remains elusive. Here, we investigated the effect of leptin receptor deficiency on metabolic dysfunction in db/db mice treated by RYGB surgery. Methods The db/db mice and their heterozygote control db/m mice were subjected to RYGB or sham surgery. Body weight, blood glucose, food intake and glucose tolerance were evaluated. Micro-PET/CT and histological analysis were performed to examine the glucose uptake of tissues and the fat changes in mice. The key factors in glucose and fatty acid metabolism were detected by western blot analysis. Results Compared with the sham group, the db/db mice in the RYGB group showed more significant weight regain after surgical recovery and improvement in hyperinsulinemia and glucose tolerance. However, the total body fat and multiple organ lipid deposition of RYGB-treated db/db mice was increased. The underlying mechanism studies suggested that the activation of AMPK regulated GLUT4 to increase glucose uptake, but AMPK could not promote fatty acid oxidation through the JAK2/STAT3 pathway under leptin receptor deficiency in db/db mice. Conclusion We conclude that leptin receptor deficiency impedes the AMPK activation-mediated fat catabolism but does not affect AMPK-related glucose utilization after metabolic surgery in db/db mice. This result helps select surgical indications for patients with obesity and diabetes.

Mineralocorticoid receptor antagonists (MRAs) for bilateral primary aldosteronism (PA) are the mainstay option recommended by guidelines, but poor compliance occurs due to numerous side effects. We aimed to examine whether catheter-based adrenal ablation could be an alternative treatment for bilateral PA.644 PA patients were included from a total of 6054 hypertensive patients. Adrenal CT scan and adrenal venous sampling (AVS) were both performed for PA subtype classification. Clinical and biochemical outcomes were assessed at 6 months after treatment according to the Primary Aldosteronism Surgical Outcome (PASO) criteria.93 patients with PA were recruited to be treated by adrenal ablation, including 25 bilateral PA and 68 unilateral PA according to AVS results. Office SBP and DBP significantly decreased from baseline levels, serum potassium levels increased and ARR significantly decreased (p < 0.01) in both the bilateral and unilateral groups. In the bilateral group, complete, partial and absent clinical success was achieved in 6 (24.0%), 11 (44.0%) and 8(32.0%) patients, respectively. In the unilateral group, complete, partial and absent clinical success was achieved in 12 (17.6%), 37 (54.4%), and 19 (27.9%) patients, respectively. The numbers of patients achieving complete, partial, and absent biochemical success were 15 (60.0%), 6 (24.0%), and 4 (16.0%), respectively, in the bilateral group versus 37 (54.4%), 9 (13.2%), and 22 (32.3%), respectively, in the unilateral group. In conclusion, we provide evidence for the beneficial outcomes of unilateral adrenal ablation for patients with bilateral PA. Our findings provide insight into an alternative option for patients with bilateral excess aldosterone.

ABSTRACTAimsTo examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM).Materials and MethodsThis cross‐sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular‐kidney‐metabolic (CKM) syndrome stage. Side‐stream dark‐field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine‐learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points.ResultsCompared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima–media thickness (IMT), brachial‐ankle pulse wave velocity (ba‐PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut‐off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA.ConclusionsSublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.

AIM:To investigate the relationship between thyroid function and weight regain in patients with obesity after metabolic surgery. METHODS:This retrospective study enrolled 162 patients who underwent metabolic surgery. Correlations between decreases in thyroid hormone levels and changes in weight, waist circumference (WC) and the Chinese visceral adiposity index (CVAI) were assessed. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cut-off values, respectively. RESULTS:The levels of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) decreased markedly at 1 year after surgery, as did weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, WC and CVAI. Decreases in TSH and FT3 after metabolic surgery were associated with changes in weight, BMI and CVAI. Binary logistic regression and ROC curve analyses confirmed that decreases in TSH can predict good weight loss after metabolic surgery to some extent. Finally, binary logistic regression and ROC curve analyses confirmed that changes in TSH can predict weight regain after metabolic surgery. CONCLUSIONS:Changes in TSH and FT3 after metabolic surgery were correlated with changes in weight and CVAI. Changes in thyroid hormones can predict weight regain in patients with obesity who underwent metabolic surgery.

Bariatric surgery (BS) is known to improve the components of metabolic syndrome (MS) in patients with obesity. However, few studies have evaluated the effect of BS on patients with MS at low BMI levels. The study aims to assess the effect of BS on MS in patients with low BMI by comparing BS with medical therapy (MT). A total of 271 patients with MS who underwent BS and MT at a single institution were reviewed in this retrospective cohort study. A 1:1 propensity score matching was performed for the BS and MT groups with BMI<35 kg/m2. We analyzed the 5 years effect of BS versus MT on the remission of MS, its components, atherosclerotic cardiovascular disease (ASCVD) risk, and medication used. Patients in the MT group showed a decrease in the prevalence of MS to 62

Objectiv: Salt-sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert hypotensive effect and cardiorenal protective benefits in hypertensive patients with and without diabetes. However, the underlying mechanism remains elusive. Methods: Dahl salt-sensitive (SS) rats and salt-insensitive controls were fed with 8% high salt diet to establish salt-sensitive hypertensive model, some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, vascular function and remodeling were detected. Rat aortic proteomics and TRPC3 knockout mice were used to explain the mechanism of the effect of canagliflozin on salt-sensitive hypertension. Results: Canagliflozin treatment significantly reduced high salt induced hypertension and this effect was not totally dependent on urinary sodium excretion in SS hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high salt diet. High salt intake increased vascular expression of TRPC3 in salt-sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt-induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the anti-hypertensive effect of canagliflozin. Mechanistically, high-salt-induced activation of sodium/calcium exchanger 1 (NCX1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin. Conclusions: We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high salt induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt sensitive hypertension.

BACKGROUND:Reducing the risk of death due to cardiovascular disease (CVD) is an important direction for diabetes prevention and treatment. The Chinese population with type 2 diabetes (T2D) has a high risk of developing CVD at relatively low body mass index (BMI) levels. Currently, no studies have evaluated the effect of bariatric surgery versus medical therapy on long-term CVD risk in patients with T2D and low BMI.OBJECTIVES:To compare bariatric surgery versus medical therapy for long-term CVD risk in Chinese patients with T2D and low BMI by using the China Prediction for ASCVD Risk equations and the United Kingdom Prospective Diabetes Study risk engine.SETTING:University hospital, China.METHODS:Medical records of patients with T2D with a BMI <35 kg/m2 undergoing bariatric surgery or medical therapy from May 2010 to December 2018 were reviewed. A 1:1 propensity score matching was performed by using 7 preoperative characteristics. Variables for calculating CVD risk scores over the 5-year follow-up were assessed.RESULTS:A total of 684 patients with T2D underwent bariatric surgery (n = 75) or medical therapy (n = 609), and 52 pairs of matched subjects were selected from both groups after propensity score matching. The 10-year and lifetime atherosclerotic CVD risk by using the China Prediction for ASCVD Risk equation at 5 years follow-up period in the bariatric surgery group improved significantly compared with the medical therapy group. In the fifth year of follow-up, the 10-year risk of coronary heart disease, fatal coronary heart disease, stroke, and fatal stroke by using the United Kingdom Prospective Diabetes Study risk engine were much lower in the bariatric surgery group than in the medical therapy group (10.37 ± 5.64% versus 27.25 ± 7.28%, P = .004; 6.3 ± 4.5% versus 22.3 ± 7.35%, P = .002; 4.97 ± 3.73% versus 15.05 ± 3.63%, P = .001; .59 ± .45% versus 1.52 ± .14%, P < .001. respectively). The use of glucose-lowering medications, including insulin, was reduced from baseline in both groups, and patients in the bariatric surgery group required significantly fewer of these medications than those in the medical therapy group.CONCLUSION:Bariatric surgery in patients with T2D and low BMI conferred a lower calculated risk of CVD compared with medical therapy over 5 years of follow-up.

Objectives To assess the benefit of a bariatric surgery in four artificial intelligence-identified metabolic (AIM) subtypes of obesity with respect to the improvement of glucometabolism and the remission of diabetes and hyperinsulinemia. Methods This multicenter retrospective study prospectively collected data from five hospitals in China from 2010 to 2021. At baseline 1008 patients who underwent a bariatric surgery were enrolled (median age 31 years; median BMI 38.1kg/m2; 57.40% women) and grouped into the four AIM subtypes. Baseline and follow-up data (506 and 359 patients at 3- and 12-month post-surgery) were collected for longitudinal effect analysis. Results Out of the four AIM subgroups, hypometabolic obesity (LMO) group was characterized by decompensated insulin secretion and high incidence of diabetes (99.2%) pre-surgery. After surgery, 62.1% of LMO patients with diabetes achieved remission, lower than the other three subgroups. Still, the bariatric surgery significantly reduced their blood glucose (median HbA1c decreased by 27.2%). The hypermetabolic obesity-hyperinsulinemia (HMO-I) group was characterized by severe insulin resistance and high incidence of hyperinsulinemia (87.8%) pre-surgery, which had been greatly alleviated post-surgery. For both metabolic healthy obesity (MHO) and hypermetabolic obesity-hyperuricemia (HMO-U) groups who showed a relatively healthy glucometabolism pre-surgery, rate of glucometabolic comorbidities improved moderately post-surgery. Conclusion In terms of glucometabolism, the four AIM subtypes of patients benefited differently from a bariatric surgery, which significantly relieved hyperglycemia and hyperinsulinemia for the LMO and HMO-I patients, respectively. The AIM-based subtypes may help better inform clinical decisions on bariatric surgery and patient counseling pertaining to post-surgery outcomes.

Unilateral adrenalectomy is the standard treatment for patients with aldosterone-producing adenoma (APA), but it lacks an option for patients with APA who refuse or are not suitable for surgery. In this study, we studied whether catheter-based adrenal ablation for APA is comparable to adrenalectomy. A total of 2185 hypertensive patients were screened, and 112 patients with APA were recruited and counselled on the treatment options. Fifty-two patients opted for catheter-based adrenal ablation, and 60 opted for adrenalectomy. Clinical and biochemical outcomes were assessed at 6 months after treatment. Factors associated with hypertension remission and the advantages and limitations of this approach were evaluated. According to the primary aldosteronism surgical outcome (PASO) criteria, complete and partial clinical success was achieved in 21 (40.4%) and 23 (44.2%) patients in the ablation group vs. 33 (55.0%) and 23 (38.3%) patients in the adrenalectomy group, respectively. Complete and partial biochemical success was achieved in 30 (57.7%) and 17 (32.7%) patients in the ablation group vs. 51 (85.0%) and 5 (8.3%) patients in the adrenalectomy group, respectively. The complete clinical success rate was not (P > 0.05), but the complete biochemical success rate was significantly different between the two groups (P < 0.01). Factors associated with adrenal ablation-mediated hypertension remission were hypertension duration and serum potassium level at baseline. Compared with surgery, adrenal ablation requires a shorter operating time and time to resume physical activity. Catheter-based adrenal ablation may be an alternative and feasible option for APA patients unwilling to receive surgical treatment.

Background Salt‐sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that SGLT2 (sodium‐glucose cotransporter 2) inhibitors exert hypotensive effect and cardiorenal protective benefits in patients with hypertension with and without diabetes. However, the underlying mechanism remains elusive. Methods and Results Dahl salt‐sensitive rats and salt‐insensitive controls were fed with 8% high‐salt diet and some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, and vascular function were detected. Transient receptor potential channel 3 (TRPC3) knockout mice were used to explain the mechanism. Canagliflozin treatment significantly reduced high‐salt‐induced hypertension and this effect was not totally dependent on urinary sodium excretion in salt‐sensitive hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high‐salt diet. High salt intake increased vascular expression of TRPC3 in salt‐sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt‐induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the antihypertensive effect of canagliflozin. Mechanistically, high‐salt‐induced activation of NCX1 (sodium‐calcium exchanger 1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin. Conclusions We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high‐salt‐induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt‐sensitive hypertension.