A road adhesion coefficient-tire cornering stiffness normalization method combining a fractional-order multi-variable gray model with a LSTM network and vehicle direct yaw-moment robust control.

A normalization method of road adhesion coefficient and tire cornering stiffness is proposed to provide the significant information for vehicle direct yaw-moment control (DYC) system design. This method is carried out based on a fractional-order multi-variable gray model (FOMVGM) and a long short-term memory (LSTM) network. A FOMVGM is used to generate training data and testing data for LSTM network, and LSTM network is employed to predict tire cornering stiffness with road adhesion coefficient. In addition to that, tire cornering stiffness represented by road adhesion coefficient can be used to built vehicle lateral dynamic model and participate in DYC robust controller design. Simulations under different driving cycles are carried out to demonstrate the feasibility and effectiveness of the proposed normalization method of road adhesion coefficient and tire cornering stiffness and vehicle DYC robust control system, respectively.

Weight loss and metabolic benefits of bariatric surgery in China: A multicenter study.

BACKGROUND: This retrospective multicenter study evaluated the efficacy and safety of bariatric surgery in Chinese patients with obesity. METHODS: Patients with obesity who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass and completed a 12-month follow-up between February 2011 and November 2019 were enrolled. Weight loss, glycemic and metabolic control, insulin resistance, cardiovascular risk, and surgery-related complications at 12 months were analyzed. RESULTS: We enrolled 356 patients aged 34.3 ± 0.6 years with a mean body mass index of 39.4 ± 0.4 kg/m2 . Successful weight loss occurred in 54.6%, 86.8%, and 92.7% of patients at 3, 6, and 12 months, respectively, with no difference in percent excess weight loss between the laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass surgery groups. The average percentage of total weight loss was 29.5% ± 0.6% at 12 months; 99.4%, 86.8%, and 43.5% of patients achieved at least 10%, 20%, and 30% weight loss, respectively, at 12 months. Significant improvements in metabolic indices, insulin resistance, and inflammation biomarkers were observed at 12 months. CONCLUSIONS: Bariatric surgery resulted in successful weight loss and improved metabolic control, insulin resistance, and cardiovascular risk in Chinese patients with obesity. Both laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are suitable approaches for such patients.

Th1 bias of liver mucosal-associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus.

AIMS: It is acknowledged that aberrant liver immunity contributes to the development of type 2 diabetes mellitus (T2DM). Mucosal-associated invariant T (MAIT) cells, an innate-like T-cell subset, are enriched in the human liver. Nevertheless, the characterisation and potential role of hepatic MAIT cells in T2DM remain unclear. MATERIALS AND METHODS: Fourteen newly diagnosed T2DM subjects and 15 controls received liver biopsy. The frequency and cytokine production of MAIT cells were analysed by flow cytometry. The expression of genes involved in glucose metabolism was determined in HepG2 cells co-cultured with hepatic MAIT cells. RESULTS: Compared with controls, hepatic MAIT cell frequency was significantly increased in T2DM patients (24.66% vs. 14.61%, p = 0.001). There were more MAIT cells producing interferon-γ (IFN-γ, 60.49% vs. 33.33%, p = 0.021) and tumour necrosis factor-α (TNF-α, 46.84% vs. 5.91%, p = 0.021) in T2DM than in controls, whereas their production of interleukin 17 (IL-17) was comparable (15.25% vs. 4.55%, p = 0.054). Notably, an IFN-γ+ TNF-α+ IL-17+/- producing MAIT cell subset was focussed, which showed an elevated proportion in T2DM (42.66% vs. 5.85%, p = 0.021) and positively correlated with plasma glucose levels. A co-culture experiment further indicated that hepatic MAIT cells from T2DM upregulated the gene expression of pyruvate carboxylase, a key molecule involved in gluconeogenesis, in HepG2 cells, and this response was blocked with neutralising antibodies against IFN-γ and TNF-α. CONCLUSIONS: Our data implicate an increased Th1-like MAIT cell subset in the liver of newly diagnosed T2DM subjects, which induces hyperglycaemia by promoting hepatic gluconeogenesis. It provides novel insights into the immune regulation of metabolic homoeostasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT03296605 (registered at www. CLINICALTRIALS: gov on 12 October 2018).

A multi-center study on glucometabolic response to bariatric surgery for different subtypes of obesity.

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.

Chronic intermittent hypoxia contributes to non-alcoholic steatohepatitis progression in patients with obesity.

BACKGROUND AND PURPOSE: The association between the severity of obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in patients with obesity remains unclear. We conducted this study to determine the effects of OSA on the severity of NAFLD in individuals with obesity and its link to the development of non-alcoholic steatohepatitis (NASH). METHODS: Patients were subjected to standard polysomnography up to 1 week before undergoing bariatric surgery, during which liver biopsy specimens were obtained. The apnea-hypopnea index (AHI) obtained by polysomnography was used to determine the severity of OSA. RESULTS: In total, 183 patients with obesity and biopsy-confirmed NAFLD were included; 49 (27%) had NASH. Patients with NASH had higher AHIs (p = 0.014) and oxygen desaturation indices (p = 0.031), more frequent OSA (p = 0.001), and lower minimum oxygen saturation (p = 0.035). The severity of OSA was directly correlated with the NAFLD activity score (p < 0.001), NASH activity grade (p < 0.001), semi-quantitative indices of lobular inflammation (p = 0.001), and hepatocyte ballooning (p = 0.006). The odds ratios (95% confidence intervals) for NASH and severe NASH (activity grade ≥ 3) associated with moderate-to-severe OSA were 3.85 (1.35-10.94; p < 0.05) and 5.02 (1.66-15.18; p < 0.01), respectively, after adjusting for sex, age, body mass index, waist circumference, insulin resistance values, and metabolic syndrome. CONCLUSIONS: Chronic intermittent hypoxia caused by OSA may aggravate NAFLD and lead to a higher risk of NASH in patients with obesity.

Comparison of Beinaglutide Versus Metformin for Weight Loss in Overweight and Obese Non-diabetic Patients.

PURPOSE: We compared the efficacy and safety of beinaglutide, a glucagon-like peptide-1 (GLP-1) analogue with metformin in lowering the bodyweight of patients who were overweight/obese and non-diabetic. PATIENTS AND METHODS: Seventy-eight non-diabetic patients were randomly selected and beinaglutide or metformin was administered for 12 weeks. The primary endpoints were changes in body weight and the proportions of patients who lost≥5 and≥10% of their baseline body weights. RESULTS: A total of 64 patients completed the study; patients in the beinaglutide group exhibited more bodyweight loss than those in the metformin group [(9.5±0.8%; 9.1±0.9 kg) and (5.1±0.9%; 4.5±0.8 kg), respectively, corresponding to a difference of approximately 4.5 kg (95% confidence interval, 2.2-6.9 kg; P<0.01)]. In the beinaglutide group, 90.6 and 40.6% of the patients lost≥5 and≥10% of their body weight, respectively, whereas, in the metformin group, these rates were 46.9 and 12.5%, respectively (P<0.01 and P<0.05). Weight loss following beinaglutide treatment mainly resulted from the loss of fat mass. Compared to metformin, beinaglutide induced a greater decrease in the body mass index, weight circumference, percent body fat, and body fat mass (total, trunk, limb, android, and gynoid). Additionally, beinaglutide decreased serum insulin levels and ameliorated insulin resistance. CONCLUSIONS: Beinaglutide is more efficient than metformin at reducing weight and fat mass in patients who are overweight/obese and non-diabetic. Beinaglutide may be a useful therapeutic option for overweight/obesity control in the Chinese population.

Machine Learning to Identify Metabolic Subtypes of Obesity: A Multi-Center Study.

Background and objective: Clinical characteristics of obesity are heterogenous, but current classification for diagnosis is simply based on BMI or metabolic healthiness. The purpose of this study was to use machine learning to explore a more precise classification of obesity subgroups towards informing individualized therapy. Subjects and Methods: In a multi-center study (n=2495), we used unsupervised machine learning to cluster patients with obesity from Shanghai Tenth People's hospital (n=882, main cohort) based on three clinical variables (AUCs of glucose and of insulin during OGTT, and uric acid). Verification of the clustering was performed in three independent cohorts from external hospitals in China (n = 130, 137, and 289, respectively). Statistics of a healthy normal-weight cohort (n=1057) were measured as controls. Results: Machine learning revealed four stable metabolic different obese clusters on each cohort. Metabolic healthy obesity (MHO, 44% patients) was characterized by a relatively healthy-metabolic status with lowest incidents of comorbidities. Hypermetabolic obesity-hyperuricemia (HMO-U, 33% patients) was characterized by extremely high uric acid and a large increased incidence of hyperuricemia (adjusted odds ratio [AOR] 73.67 to MHO, 95%CI 35.46-153.06). Hypermetabolic obesity-hyperinsulinemia (HMO-I, 8% patients) was distinguished by overcompensated insulin secretion and a large increased incidence of polycystic ovary syndrome (AOR 14.44 to MHO, 95%CI 1.75-118.99). Hypometabolic obesity (LMO, 15% patients) was characterized by extremely high glucose, decompensated insulin secretion, and the worst glucolipid metabolism (diabetes: AOR 105.85 to MHO, 95%CI 42.00-266.74; metabolic syndrome: AOR 13.50 to MHO, 95%CI 7.34-24.83). The assignment of patients in the verification cohorts to the main model showed a mean accuracy of 0.941 in all clusters. Conclusion: Machine learning automatically identified four subtypes of obesity in terms of clinical characteristics on four independent patient cohorts. This proof-of-concept study provided evidence that precise diagnosis of obesity is feasible to potentially guide therapeutic planning and decisions for different subtypes of obesity. Clinical Trial Registration: www.ClinicalTrials.gov, NCT04282837.

Lixisenatide is effective and safe as add-on treatment to basal insulin in Asian individuals with type 2 diabetes and different body mass indices: a pooled analysis of data from the GetGoal Studies.

INTRODUCTION: This analysis aims to investigate the efficacy and safety of once-daily lixisenatide add-on treatment to basal insulin in Asian individuals with type 2 diabetes, by baseline body mass index (BMI). RESEARCH DESIGN AND METHODS: Data from all Asian participants in the placebo-controlled GetGoal-Duo 1, GetGoal-L, and GetGoal-L-C Studies were pooled and categorized according to the following BMI subgroups:<25 kg/m2, 25-<30 kg/m2 and ≥30 kg/m2. Efficacy and safety of lixisenatide versus placebo were evaluated among BMI subgroups. Multivariable regression analyses were also conducted to explore the potential influence of BMI on efficacy outcomes after adjusting for baseline characteristics. RESULTS: 555 participants were included (mean age 53.9 years, 52.4% men). No significant differences in treatment effect between the BMI subgroups were observed for the changes from baseline to 24 weeks in glycated hemoglobin (HbA1c), fasting plasma glucose, postprandial glucose (PPG), PPG excursion, body weight, BMI, and basal insulin dose with lixisenatide, as well as the change in basal insulin dose at study endpoint and the proportion of participants achieving an HbA1c <7% at 24 weeks (all p values for interaction >0.15). In the multivariable regression analysis, participants in the lowest BMI group had a smaller reduction in body weight over the 24-week treatment period relative to the highest BMI group (p=0.023). CONCLUSIONS: This post hoc analysis indicates that lixisenatide improved glycemic control regardless of baseline BMI and was well tolerated in Asian individuals unable to achieve their HbA1c target on basal insulin±oral antidiabetic drugs.

Body Adiposity Index Is Predictive of Weight Loss after Roux-en-Y Gastric Bypass.

BACKGROUND/AIMS: Roux-en-Y gastric bypass (RYGB) is one of the most effective therapies for morbid obesity, yet some patients who have taken the surgery still undergo insufficient weight loss. Visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI), and cardiometabolic index (CMI) have been regarded as clinical indicators of adiposity phenotypes that associated closely with obesity-related metabolic diseases. However, no studies have evaluated the relationship between these indexes and weight loss after bariatric surgery. In this prospective study, we aimed to evaluate whether VAI, LAP, BAI, and CMI would predict postoperative weight loss outcomes after RYGB. METHODS: This study included 38 men and 67 women who have undergone RYGB between January 2017 and May 2018 and recorded their %TWL (percent of total weight loss), %EBMIL (percent of excess body mass index loss), %EWL (percent of excess weight loss), anthropometric indices, and biochemical parameters before and 12 months after the surgery. In addition, VAI, LAP, BAI, and CMI were measured with anthropometric measures or lipid profiles using related equations and analyzed with metabolic characteristics. RESULTS: Subjects with lower BAI (<32.54 in men and 37.39 in women) displayed higher %EBMIL and %EWL 12 months after surgery. BAI was independently associated with %EWL 12 months after surgery in both men and women (both p < 0.05). The area under the receiver operating characteristic curve for BAI was significantly higher (0.773 in men and 0.818 in women) than VAI, LAP, and CMI. CONCLUSIONS: BAI serves as a reliable surrogate marker of the weight loss outcome after RYGB. The predictivity of adiposity indexes in beneficial outcomes after weight loss therapies is of important referential value for the implementation and optimization of individualized and refined weight loss treatments for obese patients.

Association of Omental Adipocyte Hypertrophy and Fibrosis with Human Obesity and Type 2 Diabetes.

OBJECTIVE: Morphological alterations including adipocyte hypertrophy and fibrosis deposition are important surrogate markers of visceral adipose tissue function, but the relationships between these morphological changes and type 2 diabetes mellitus (T2DM) and impaired insulin sensitivity are poorly defined. METHODS: Omental adipose tissue was obtained from 66 individuals with obesity but without T2DM (OB group), 93 individuals with both obesity and T2DM (T2DM group), and 15 individuals with normal BMI and normal glucose tolerance (NGT group). Adipocyte diameter and volume were measured through pathological section analysis. Pericellular and perilobular fibrosis was determined through picrosirius red staining and immunochemistry, while fibrosis-related genes were tested through gene expression and hydroxyproline content. RESULTS: Compared with the NGT and OB groups, individuals from the T2DM group displayed increased adipocyte diameter and volume levels. Increased adipocyte size (diameter and volume) was positively associated with hyperglycemia and insulin resistance and inversely correlated with insulin sensitivity (using the Matsuda whole-body insulin sensitivity index assessment of insulin sensitivity) and ß-cell function (disposition index 30 and disposition index 120). The fibrosis levels of the OB group were the highest out of the three groups, whereas the fibrosis levels of T2DM individuals were lower than the OB group but higher than the NGT group. Although fibrosis was negatively correlated with T2DM, fibrosis deposition was not remarkably associated with impaired systemic insulin sensitivity and glucose metabolism. CONCLUSIONS: Compared with fibrosis deposition, adipocyte hypertrophy is more closely associated with T2DM and impaired systemic insulin sensitivity.

Silymarin ameliorates the disordered glucose metabolism of mice with diet-induced obesity by activating the hepatic SIRT1 pathway.

Obesity-induced insulin resistance is the principal cause of type 2 diabetes worldwide. The use of natural products for the treatment of diabetes is increasingly attracting attention. Silymarin (SLM) is a flavonolignan compound that has been shown to have promise for the treatment of diabetes. In the present study, we aimed to investigate the mechanisms underlying its therapeutic effects. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and then orally administered SLM (30 mg/kg) daily for 1 month. The effects of SLM were also investigated in HepG2 cells that had been rendered insulin resistant by palmitic acid (PA) treatment. SLM ameliorated the dyslipidemia, hepatic steatosis, and insulin resistance of the HFD-fed mice. HFD-feeding and PA treatment reduced the expression of sirtuin-1 (SIRT1) in the livers of the mice and in HepG2 cells, respectively. SLM increased the phosphorylation of AKT and FOXO1, and reduced the level of FOXO1 acetylation in PA-treated cells. However, SIRT1 knockdown by RNA interference reduced these effects of SLM. Moreover, the results of molecular dynamic simulation and in vitro activity assays indicated that SLM may directly bind to SIRT1 and increase its enzymatic activity. These findings suggest that hepatic SIRT1 may be an important pharmacological target of SLM and mediate effects on insulin resistance and gluconeogenesis, which may underlie its anti-diabetic activity.

Efficacy and safety of LY2963016 insulin glargine versus insulin glargine (Lantus) in Chinese adults with type 2 diabetes: A phase III, randomized, open-label, controlled trial.

AIM: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) with insulin glargine (Lantus; IGlar) combined with oral antihyperglycaemic medications (OAMs) in insulin-naive Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this phase III, open-label trial, adult patients with T2D receiving two or more OAMs at stable doses for 12 weeks or longer, with HbA1c of 7.0% or more and 11.0% or less, were randomized (2:1) to receive once-daily LY IGlar or IGlar for 24 weeks. The primary outcome was non-inferiority of LY IGlar to IGlar at a 0.4% margin, and a gated secondary endpoint tested non-inferiority of IGlar to LY IGlar (-0.4% margin), assessed by least squares (LS) mean change in HbA1c from baseline to 24 weeks. RESULTS: Patients assigned to LY IGlar (n = 359) and IGlar (n = 177) achieved similar and significant reductions (p < .001) in HbA1c from baseline. LY IGlar was non-inferior to IGlar for change in HbA1c from baseline to week 24 (-1.27% vs. -1.23%; LS mean difference: -0.05% [95% CI, -0.19% to 0.10%]) and IGlar was non-inferior to LY IGlar. The study therefore showed equivalence of LY IGlar and IGlar for the primary endpoint. At week 24, there were no between-group differences in the proportion of patients achieving an HbA1c of less than 7.0%, seven-point self-measured blood glucose, insulin dose or weight gain. Adverse events, allergic reactions, hypoglycaemia and insulin antibodies were similar in the two groups. CONCLUSIONS: Once-daily LY IGlar and IGlar, combined with OAMs, provide effective and similar glycaemic control with comparable safety profiles in insulin-naive Chinese patients with T2D.

Are Chinese Patients with Type 2 Diabetes and a Body Mass Index of 27.5-32.5 kg/m2 Suitable for Metabolic Surgery? A One-Year Post-Surgery Study.

INTRODUCTION: The aim of this study was to clarify the efficacy and safety of metabolic surgery in Chinese patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 27.5-32.5 kg/m2. METHODS: A total of 99 patients with T2DM were enrolled in this retrospective cohort study. Of these patients, 53 had a BMI of 27.5-32.5 kg/m2 and had undergone metabolic surgery (n = 21) or were on conventional antidiabetic therapy (n = 32)]; 46 had a BMI ≥ 32.5 kg/m2 and all had undergone metabolic surgery. Primary endpoints included the triple endpoint [hemoglobin A1c < 6.5%, low-density lipoprotein cholesterol (LDL-C) < 2.6 mmol/L, and systolic blood pressure (SBP) < 130 mmHg] and successful weight loss 1 year later. Remission of diabetes, glucose and lipid metabolism, medication usage, and adverse events were evaluated. RESULTS: Of patients with BMI 27.5-32.5 kg/m2 undergoing metabolic surgery, 33.33% achieved the composite endpoints, and 100% achieved successful weight loss. This result was similar to that in patients with BMI ≥ 32.5 and better than those with BMI 27.5-32.5 kg/m2 receiving conventional antidiabetic therapy. A significant and similar reduction in BMI, waist circumference, SBP, serum LDL-C, hemoglobin A1c, and uric acid, as well as similar frequency postoperative adverse events, were confirmed in both metabolic surgery groups. Patients with BMI 27.5-32.5 kg/m2 who had undergonemetabolic surgery showed more metabolic improvement than those only receiving medications but they experienced more adverse events. CONCLUSION: A BMI cutoff of 27.5 kg/m2 for metabolic surgery may be suitable for Chinese patients with T2DM.

Oxygen therapy alleviates hepatic steatosis by inhibiting hypoxia-inducible factor-2α.

Non-alcoholic fatty liver disease (NAFLD) is difficult to manage due to the lack of effective treatments. Increased oxygen consumption caused by overnutrition, along with reduced oxygen delivery to liver cells induces hepatic steatosis. Here, we investigated the efficacy of oxygen therapy (OT) to alleviate hepatic steatosis. The effect of OT on hepatic steatosis was evaluated in high-fat-diet (HFD)-fed mice and palmitic acid (PA)-treated primary hepatocytes. Liver biopsy tissue samples were used to determine the relationship between the expression of hypoxia-inducible factor-2α (HIF-2α) and the progression of NAFLD. The role of HIF-2α in the OT group was determined based on the overexpression of HIF-2α in vitro. OT safely alleviated hepatic hypoxia and improved hepatic steatosis by inhibiting hepatic de novo lipogenesis in HFD-fed mice and PA-treated primary hepatocytes, and this was accompanied by reduced expression of HIF-2α and hepatic de novo lipogenesis. The analysis of liver tissues from individuals with or without NAFLD revealed a positive correlation between hepatic HIF-2α expression and NAFLD progression. Overexpression of HIF-2α in vitro inhibited the beneficial effect of OT against hepatic lipogenesis and steatosis. OT might be a viable treatment option for NAFLD and functions by alleviating hypoxia and inhibiting the liver HIF-2α signaling pathway.

Liraglutide Attenuates Nonalcoholic Fatty Liver Disease by Modulating Gut Microbiota in Rats Administered a High-Fat Diet.

This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.

Correction to: A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels.

Following publication of the original article [1], we have been notified that the given name of one of the authors was spelled incorrectly.

A newly noninvasive model for prediction of non-alcoholic fatty liver disease: utility of serum prolactin levels.

BACKGROUNDS: To investigate the value of prolactin (PRL) in diagnosing non-alcoholic fatty liver disease (NAFLD). METHODS: Metabolic parameters and serum PRL levels were measured in 452 males and 421 females, who were randomized to the estimation or the validation group as a 1:1 ratio. Hepatic steatosis was diagnosed via abdominal ultrasound. Variables that significantly associated with NAFLD in univariate analysis were included in multiple logistic regression. We used the receiver operator characteristic (ROC) curves to test the model performance. Besides, 147 patients underwent metabolic and liver biopsy were analyzed to validate the diagnostic value of this model. RESULTS: Body mass index, alanine aminotransferase, prolactin, high density lipoprotein cholesterol and HbA1c were included into models. In males, the area under ROC curve (AUC) was 0.86 (95%CI: 0.82-0.91) for the validation group. With two cut-off points (- 0.79 and 1.71), the sensitivity and specificity for predicting NALFD was 95.2 and 91.1% in the validation group, respectively. In females, the AUC was 0.82 (95%CI: 0.76-0.88) for the validation group. With two cut-off points (- 0.68 and 2.16), the sensitivity and specificity for predicting NALFD was 97.1 and 91.4% in the validation group, respectively. In subjects with liver pathology, the AUC was higher than that of fatty liver index. A positive correlation between the scores of the model and the severities of NAFLD was observed. Importantly, we demonstrated a potential value of this model in predicting nonalcoholic steatohepatitis. CONCLUSION: We established a mathematic model that can conveniently and effectively diagnose the existence and severities of NAFLD.

Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity.

Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c+ macrophage activation. Reconstruction of the adipose ILC1 population in Prkdc-/-IL2rg-/- mice by adoptive transfer drives adipose fibrogenesis through activation of TGFß1 signaling; however, transfer of Ifng-/- ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.

The captopril challenge test for diagnosing primary Aldosteronism in a Chinese population.

BACKGROUND: The Captopril challenge test (CCT) is an easy-conduct confirmatory test for diagnosing primary aldosteronism (PA). Guidelines show that plasma aldosterone is normally suppressed by captopril (> 30%) in primary hypertension (PH) and in healthy people. It is unclear whether this standard is applicable in Chinese subjects. The aim of the present study was to investigate the post-CCT efficacy of plasma aldosterone concentration (PAC) suppression and determine the post-CCT aldosterone renin activity ratio (ARR) and PAC for PA diagnosis. METHODS: We recruited 110 consecutive patients with PA, 163 with primary hypertension (PH), and 40 healthy volunteers (NC). The CCT was conducted in all patients. Total sodium intake was estimated from 24-h urinary excretions. ROC curves were used to analyze the efficiency of different CCT diagnostic criteria for diagnosing PA. RESULTS: In NC and PH patients, PRA was increased and PAC was decreased post-CCT (P < 0.05). The mean degree of PAC decline after CCT was approximately 9.3%, and only 11.7% of the patients with PH showed a greater than 30% suppression of PAC after CCT. In patients with PA, the post-CCT change in PRA and PRC was slight. The post-CCT degree of PAC decline was unrelated to dietary salt intake. The areas under the ROC for the post-CCT ARR, PAC and PAC suppression % were 0.994, 0.754 and 0.606, respectively. The optimal post-CCT cutoff value for ARR for diagnosing PA was 20, which yielded a sensitivity and specificity of 94.0 and 99.4%, respectively. CONCLUSIONS: The PAC suppression percentage after CCT recommended by current clinical guidelines is not applicable when diagnosing Chinese subjects with PA. Compared to post-CCT PAC, post-CCT ARR was a better approach, having an optimal cutoff of 20 when interpreting the results of the CCT in Chinese patients. We found no relationship between high salt intake and low responses of the renin-angiotensin system (RAS) to the CCT.

Metabolic effects and safety of Roux-en-Y gastric bypass surgery vs. conventional medication in obese Chinese patients with type 2 diabetes.

AIM: To assess metabolic effects and safety of Roux-en-Y gastric bypass (RYGB) versus conventional medication (CM) in obese Chinese patients with type 2 diabetes (T2DM). METHODS: This retrospective cohort study included 40 patients who underwent RYGB (mean age 44.1 years, body mass index [BMI] 33.3 kg/m2 ) and 36 patients administered CM (mean age 49.4 years, BMI 32.1 kg/m2 ). The primary endpoint was achievement of the triple endpoint (haemoglobin A1C [HbA1c] < 7.0%, low-density lipoprotein cholesterol < 2.6 mmol/L, and systolic blood pressure < 130 mmHg). Changes in weight, BMI, medication usage, complications, and adverse events were assessed. RESULTS: After 1-year follow-up, 35% of RYGB patients and 8% of CM patients achieved the triple endpoint (P = 0.005). More patients in the RYGB group achieved complete (48% vs 3%, P < 0.001) and partial (23% vs 0%, P = 0.007) remission of diabetes, and complete remission of hypertension (58% vs 24%, P = 0.019). Patients in the RYGB group had greater weight loss and decrease in BMI, waist circumference, fasting and postprandial of blood glucose and insulin levels, HbA1c, blood pressure, triglycerides, and increased high-density cholesterol (P < 0.001- < 0.05). A lower proportion of the RYGB group received antidiabetics, antihypertensives, or antilipemic treatments, and had non-alcoholic fatty liver disease (NAFLD) than the CM group during follow-up. More patients had nutrient deficiency-related diseases in the RYGB group over 1-year follow-up. CONCLUSIONS: For obese Chinese patients with T2DM, RYGB resulted in better metabolic control, greater weight loss, and lower medication usage and NAFLD, but more frequently resulted in diseases related to nutrient deficiency.