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Background: Non-obese patients with diabetes mellitus (DM) are becoming more prevalent, but their cardiovascular risk (CV) especially when accompanied with cardio-renal-metabolic co-morbidities (hypertension, chronic kidney disease, hyperlipidemia) is not well characterised. The aim of the study was to assess the CV risk among patients with DM in relation to obesity and cardio-renal-metabolic co-morbidities. Materials and methods: This was a cohort study of all patients with DM without a history of major adverse cardiovascular event who were hospitalized for any reason in France in 2013 with at least 5 years of follow-up. They were categorized by the presence of obesity vs no obesity, as well as three cardio–renal–metabolic co-morbidities: hypertension, chronic kidney disease, hyperlipidemia. 'Extremely unhealthy' patients with DM were defined as those having all 3 co-morbidities. Results: There were 196,112 patients (mean age 65.7 (SD 13.7) years; 54.3% males) included into the analysis. During a mean follow-up of 4.69 ± 1.79 years, when adjusted for multiple covariates, the non-obese and 'extremely unhealthy' obese patients had the highest risk of CV death [aHR 1.40 (95% CI, 1.22–1.61) and 1.48 (95% CI, 1.25–1.75), respectively]. The 'extremely unhealthy' obese had the highest risk of MACE-HF [aHR 1.84 (95% CI, 1.72–1.97)] and new-onset AF [aHR 1.64 (95% CI, 1.47–1.83)]. Conclusion: Both non-obese and obese patients with DM with associated cardio-renal-metabolic co-morbidities are an 'extremely unhealthy' phenotype with the highest risk of CV death and CV events. [ABSTRACT FROM AUTHOR]

Background: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in patients with chronic hepatitis B (CHB). NAFLD is typically associated with obesity, however, it is increasingly being identified in non-obese patients. This study aimed to investigate disease severity and antiviral response in non-obese patients with CHB with NAFLD (CHB + NAFLD). Methods: A total of 809 patients with CHB + NAFLD were prospectively recruited and followed up for 3 years. NAFLD was diagnosed by transient elastography and defined as controlled attenuation parameter ≥248 dB/m, in the absence of excessive alcohol intake. Obesity status was defined by the Asian body mass index (BMI) cutoff of 25 kg/m2. Metabolic abnormality was defined by the presence of dyslipidemia, hypertension or diabetes. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1-stage increment. Results: In the total cohort (median age 40 years, 59.0% antiviral-treated), 33.3% were non-obese. Non-obese patients were less metabolically abnormal than obese patients (60.2% vs 72.0%, P = 0.003). After 3-year follow up, the rate of fibrosis progression was comparable between non-obese and obese patients (17.5% vs 21.9% in the total cohort, P = 0.145; 15.7% vs 14.6% in antiviral-treated cohort with persistent viral suppression, P = 0.795). No significant differences in virological and biochemical responses were observed between non-obese and obese patients (P >0.05 for all). Conclusion: Approximately one third of CHB + NAFLD patients were non-obese. Non-obese patients, while less metabolically abnormal, had a similar risk for fibrosis progression as obese patients. Obesity status did not impact the efficiency of antiviral therapy.

The prevalence of non-obese individuals with insulin resistance (IR) and type 2 diabetes (T2D) is increasing worldwide. This study investigates the metabolic signature of phospholipid-associated metabolites in non-obese individuals with IR and T2D, aiming to identify potential biomarkers for these metabolic disorders. The study cohort included non-obese individuals from the Qatar Biobank categorized into three groups: insulin sensitive, insulin resistant, and patients with T2D. Each group comprised 236 participants, totaling 708 individuals. Metabolomic profiling was conducted using high-resolution mass spectrometry, and statistical analyses were performed to identify metabolites associated with the progression from IS to IR and T2D. The study observed significant alterations in specific phospholipid metabolites across the IS, IR, and T2D groups. Choline phosphate, glycerophosphoethanolamine, choline, glycerophosphorylcholine (GPC), and trimethylamine N-oxide showed significant changes correlated with disease progression. A distinct metabolic signature in non-obese individuals with IR and T2D was characterized by shifts in choline metabolism, including decreased levels of choline and trimethylamine N-oxide and increased levels of phosphatidylcholines, phosphatidylethanolamines, and their degradation products. These findings suggest that alterations in choline metabolism may play a critical role in the development of glucose intolerance and insulin resistance. Targeting choline metabolism could offer potential therapeutic strategies for treating T2D. Further research is needed to validate these biomarkers and understand their functional significance in the pathogenesis of IR and T2D in non-obese populations. [ABSTRACT FROM AUTHOR]

The burden of nonalcoholic fatty liver disease (NAFLD) is growing in patients with chronic hepatitis B (CHB). NAFLD is typically associated with obesity, however, it is increasingly being identified in non-obese patients. This study aimed to investigate disease severity and antiviral response in non-obese patients with CHB with NAFLD (CHB + NAFLD). A total of 809 patients with CHB + NAFLD were prospectively recruited and followed up for 3 years. NAFLD was diagnosed by transient elastography and defined as controlled attenuation parameter ≥248 dB/m, in the absence of excessive alcohol intake. Obesity status was defined by the Asian body mass index (BMI) cutoff of 25 kg/m2. Metabolic abnormality was defined by the presence of dyslipidemia, hypertension or diabetes. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1-stage increment. In the total cohort (median age 40 years, 59.0% antiviral-treated), 33.3% were non-obese. Non-obese patients were less metabolically abnormal than obese patients (60.2% vs 72.0%, P = 0.003). After 3-year follow up, the rate of fibrosis progression was comparable between non-obese and obese patients (17.5% vs 21.9% in the total cohort, P = 0.145; 15.7% vs 14.6% in antiviral-treated cohort with persistent viral suppression, P = 0.795). No significant differences in virological and biochemical responses were observed between non-obese and obese patients (P >0.05 for all). Approximately one third of CHB + NAFLD patients were non-obese. Non-obese patients, while less metabolically abnormal, had a similar risk for fibrosis progression as obese patients. Obesity status did not impact the efficiency of antiviral therapy. [ABSTRACT FROM AUTHOR]

Background & aimsLean patients with non-alcoholic fatty liver disease (NAFLD) represent 10-20% of the affected population and may have heterogeneous drivers of disease. We have recently proposed the evaluation of patients with lean NAFLD without visceral adiposity for rare monogenic drivers of disease. Here, we aimed to validate this framework in a well-characterised cohort of patients with biopsy-proven NAFLD by performing whole exome sequencing.MethodsThis prospective study included 124 patients with biopsy-proven NAFLD and paired liver biopsies who underwent standardised research visits including advanced magnetic resonance imaging (MRI) assessment of liver fat and stiffness.ResultsSix patients with lean NAFLD were identified and underwent whole exome sequencing. Two lean patients (33%) were identified to have monogenic disorders. The lean patients with monogenic disorders had similar age, and anthropometric and MRI characteristics to lean patients without a monogenic disorder. Patient 1 harbours a rare homozygous pathogenic mutation in ALDOB (aldolase B) and was diagnosed with hereditary fructose intolerance. Patient 2 harbours a rare heterozygous mutation in apolipoprotein B (APOB). The pathogenicity of this APOB variant (p.Val1856CysfsTer2) was further validated in the UK Biobank and associated with lower circulating APOB levels (beta = -0.51 g/L, 95% CI -0.65 to -0.36 g/L, p = 1.4 × 10-11) and higher liver fat on MRI (beta = +10.4%, 95% CI 4.3-16.5%, p = 8.8 × 10-4). Hence, patient 2 was diagnosed with heterozygous familial hypobetalipoproteinaemia.ConclusionsIn this cohort of well-characterised patients with lean NAFLD without visceral adiposity, 33% (2/6) had rare monogenic drivers of disease, highlighting the importance of genomic analysis in this NAFLD subtype.Impact and implicationsAlthough most people with non-alcoholic fatty liver disease (NAFLD) are overweight or obese, a subset are lean and may have unique genetic mutations that cause their fatty liver disease. We show that 33% of study participants with NAFLD who were lean harboured unique mutations that cause their fatty liver, and that these mutations had effects beyond the liver. This study demonstrates the value of genetic assessment of NAFLD in lean individuals to identify distinct subtypes of disease.

Studies investigating the effect of trunk inclination on respiratory mechanics in mechanically ventilated patients with ARDS have reported postural differences in partition respiratory mechanics. Compared with more upright positions, the supine-flat position provided lower lung and chest wall elastance, allowing reduced driving pressures and end-inspiratory transpulmonary pressure. However, the effect of trunk inclination on respiratory mechanics in patients with obesity and ARDS is uncertain. Does the effect of change in posture on partition respiratory mechanics differ between patients with ARDS with and without obesity? In this single-center study, patients with ARDS with and without obesity were randomized into two 15-minute steps in which trunk inclination was changed from semi-recumbent (40° head up) to supine-flat (0°), or vice versa. At the end of each step partition respiratory mechanics, airway opening pressure and arterial blood gases were measured. Paired t test was used to examine respiratory mechanics and blood gas variables in each group. Forty consecutive patients were enrolled. Twenty were obese (BMI, 38.4 [34.5-42.3]), and 20 were non-obese (BMI, 26.6 [25.2-28.5]). In the patients with obesity, lung and chest wall elastance, driving pressure, inspiratory transpulmonary pressure, Pa co 2 , and ventilatory ratio were lower supine than semi-recumbent (P <.001). Airways resistance was greater supine (P =.006). In the patients without obesity, only chest wall elastance was lower in supine vs semi-recumbent (P <.001). In mechanically ventilated patients with ARDS and obesity, supine posture provided lower lung and chest wall elastance, and better CO 2 clearance, than the semi-recumbent posture. This study was registered with Australian New Zealand Clinical Trials Registry (ACTRN12623000794606). [Display omitted] [ABSTRACT FROM AUTHOR]

Wenying Yi,1,2 Haibo Wu,1,2 Weibin Fu,1,2 Huimei Feng,1,2 Jie Huang,1,2 Haijing Li,1,2 Zhen Song,1,2 Yuwei Chen,1,2 Yingjun Zheng,1,2 Shenglin She1,2 1Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shenglin She, Department of Psychiatry, the Affiliated Brain Hospital of Guangzhou MedicalUniversity, No. 36 Mingxin Road, Liwan District, Guangzhou, People’s Republic of China, Tel +86-13825154669, Fax +86-20-82068107, Email shenglinshe@gzhmu.edu.cnBackground: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China.Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m2 was considered obese, and BMI < 25 kg/m2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University.Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients.Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia.Keywords: schizophrenia, NAFLD, non-obese, obese, risk factors, China

Shuping Ruan,&ast; Xiaoqing Yuan,&ast; Juan Liu, Qing Zhang, Xinhua Ye Department of Endocrinology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Zhang; Xinhua Ye, Email 1034173982@qq.com; Endocrine1314@163.comPurpose: This study aims to investigate cardiovascular risk factors in nonobese patients with type 2 diabetes (T2DM) and non-alcoholic fatty liver disease (NAFLD) and to determine whether they might be used to predict high-risk individuals effectively.Patients and Methods: This cross-sectional study included 245 nonobese patients with T2DM who underwent FibroTouch in the National Metabolic Management Center of the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University from January 2021 to December 2022. All individuals were divided into NAFLD and non-NAFLD groups. Patients with NAFLD were further grouped by UAP tertiles (T1, T2 and T3). We created a Cardiovascular Score (total scale: 0– 5 points; ≥ 3 points was defined as high-risk individual) based on baPWV, carotid ultrasound, and urinary microalbumin creatinine ratio (UA/CR) to assess the risk of cardiovascular disease in non-obese T2DM patients with NAFLD. Risk factors were evaluated using univariate and multivariate analysis. The performance of risk factors was compared according to the area under the receiver operating characteristic (ROC) curve.Results: Atherogenic index of plasma (AIP), atherosclerosis index (AI), prevalence of hypertension, body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR) were higher in the NAFLD group compared to the non-NAFLD group. In T3 group, AIP, AI, BMI and HOMA-IR were higher than those of T1 group. Multivariate logistic regression showed that age, systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C) and AIP were risk factors for cardiovascular disease among nonobese patients with T2DM and NAFLD. The area under the ROC curve for age, systolic blood pressure, LDL-C and AIP were 0.705, 0.688, 0.738 and 0.642, respectively. The area under the ROC curve was 0.895 when combining them.Conclusion: Age, systolic blood pressure, AIP and LDL-C are all independent risk factors for cardiovascular disease in non-obese individuals with T2DM and NAFLD, which can be combined to identify high-risk populations and carry out intervention.Keywords: T2DM, non-obese, NAFLD, cardiovascular disease

Background/purpose: Metabolic-associated fatty liver disease (MAFLD) is a major cause of chronic liver disease worldwide and is generally thought to be closely related to obesity and diabetes. However, it also affects non-obese individuals, particularly in Asian cultures. Methods: Healthy physical examination subjects and MAFLD patients were included in the endocrinology department of Jiangsu Provincial Hospital of Traditional Chinese Medicine. MAFLD was defined as fatty liver in imaging without virus infection, drug, alcohol, or other known causes of chronic liver disease. Non-obese MAFLD was defined as MAFLD in non-obese subjects (BMI<25 kg/m2). Results: The final analysis comprised 1047 participants in total. Of 946 MAFLD patients, 162 (17.12%) were diagnosed with non-obese MAFLD. Non-obese MAFLD patients were older, had lower alanine aminotransferase (ALT), triglyceride, and waist circumference, but had higher high density lipoprotein cholesterol (HDL-c) than obese MAFLD patients. Compared with non-obese healthy controls, non-obese MAFLD patients had higher BMI, ALT, gammaglutamyl transferase (GGT), uric acid (UA), triglycerides (TG), and low density lipoprotein cholesterol (LDL-c). In terms of body composition, body fat mass (BFM), waist-hip ratio (WHR), percent body fat (PBF), visceral fat area (VFA), and fat mass index (FMI) were lower in non-obese healthy controls than non-obese MAFLD patients. A binary logistic regression analysis revealed that non-obese MAFLD was linked with lower GGT and higher HDL-c. Conclusion: In this study cohort, non-obese MAFLD was present at a prevalence of 13.90%. In contrast to non-obese healthy controls, non-obese MAFLD patients exhibited different metabolic profiles, but they also had different body compositions. [ABSTRACT FROM AUTHOR]

Aim: Metabolic dysfunction is a risk factor for esophageal squamous cell carcinoma (ESCC). We investigated the impact of the recently proposed metabolic dysfunction‐associated fatty liver disease (MAFLD) and its subtypes on ESCC recurrence after endoscopic treatment. Methods: This multicenter observational cohort study enrolled consecutive patients newly diagnosed with ESCC after endoscopic treatment. Patients were classified into MAFLD or non‐MAFLD groups. The MAFLD group was further classified into non‐obese and obese MAFLD groups with a body mass index cutoff value of 25 kg/m2. The impact of MAFLD on the recurrence of ESCC was evaluated using a decision tree algorithm and random forest analysis. Results: A total of 147 patients (average age 69 years; male : female, 127:20; observational period, 2.4 years) were enrolled. The 1‐, 3‐, and 5‐year recurrence rates were 2.0%, 21.1%, and 33.7%, respectively. Independent risk factors for the recurrence of ESCC were MAFLD (HR 2.2812; 95% confidence interval 1.0497–4.9571; p = 0.0373), drinking status, and smoking status. Metabolic dysfunction‐associated fatty liver disease was identified as the second most important classifier for recurrence, followed by drinking status. The cumulative incidence of ESCC recurrence was higher in the MAFLD group than in the non‐MAFLD group. In a subanalysis, the cumulative incidence of recurrence was significantly higher in the non‐obese than in the obese MAFLD group among abstainers/non‐drinkers. Directed acyclic graphs revealed that MAFLD directly contributes to ESCC recurrence. Conclusions: MAFLD was independently and directly associated with ESCC recurrence after endoscopic treatment; a high recurrence rate was observed in patients with non‐obese MAFLD. Metabolic dysfunction‐associated fatty liver disease may identify patients at high risk for ESCC recurrence. [ABSTRACT FROM AUTHOR]

Objective: Many studies are interested in the association between non-alcoholic fatty liver disease (N-AFLD) and other parameters. Our study evaluated the association between serum uric acid (SrUA) levels and N-AFLD in non-diabetic non-obese adults. Methods: In this study, 50 patients and 50 control subjects were enrolled to investigate the association between SrUA and N-AFLD in adults. The Kruskal-Wallis test was used to compare SrUA values according to ultrasonographic liver fat levels. Results: A statistically significant difference was found between the N-AFLD and control subjects according to the mean SrUA level (p<0.001). In the N-AFLD group, a positive relationship was found between SrUA levels and homeostasis model assessment of insulin resistance values (r=0.35, p<0.001). Conclusion: In this study, an important positive relationship was detected between SrUA levels and N-AFLD and insulin resistance. [ABSTRACT FROM AUTHOR]

Clinical data on the prevalence of metabolic-associated fatty liver disease (MAFLD) in obese and non-obese individuals within a diverse US population is scarce. Furthermore, the influence of physical activity (PA) and dietary quality (DQ) on MAFLD risk remains unclear. This study aims to assess the prevalence and clinical features of MAFLD and examine the relationship between PA and DQ with the risk of developing MAFLD. A cross-sectional analysis of data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) was conducted. The overall MAFLD prevalence was 41.9%, with 28.6% of participants being obese and 13.4% non-obese. Among those with MAFLD, 67.1% (95% confidence interval (CI): 59.1%–75.1%) were obese, and 32.9% (95% CI: 29.1%–36.7%) were non-obese. Non-obese MAFLD was more frequent in Asians (27.2%), while obese MAFLD was more prevalent in Blacks (66.3%). Metabolic comorbidities were more common in individuals with obese MAFLD, who also exhibited more advanced fibrosis. A high-quality diet (HQD) and increased PA were linked to reduced odds of both obese and non-obese MAFLD (odds ratio (OR) and 95% CI: 0.67 [0.51–0.88] and 0.57 [0.47–0.69]; 0.62 [0.43–0.90] and 0.63 [0.46–0.87], respectively). PA and HQD significantly decreased the risk of obese and non-obese MAFLD (OR and 95% CI: 0.46 [0.33–0.64] and 0.42 [0.31–0.57]). A substantial proportion of the US population is affected by both obese and non-obese MAFLD. A strong association exists between a lower risk of both types of MAFLD and adherence to an HQD and engagement in PA. • This study examines the prevalence of metabolic-associated fatty liver disease (MAFLD) in obese and non-obese individuals within a diverse US population using data from the 2017–2018 NHANES. • The overall MAFLD prevalence was found to be 41.9%, with 28.6% of participants being obese and 13.4% non-obese. • Both dietary quality and physical activity were strongly associated with a lower risk of obese and non-obese MAFLD. • Socioeconomic status, education, and household income were found to be related to MAFLD risk, with higher levels of these factors associated with healthier diets and increased physical activity. • The study highlights the importance of lifestyle interventions in the prevention and management of MAFLD, underscoring the need for healthcare professionals to address these factors in both obese and non-obese individuals. • Despite the study's limitations, including self-reported measures and small sample sizes for certain subgroups, it contributes valuable insights into the complex interactions between obesity, lifestyle factors, and the development of MAFLD. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris (AV) is a chronic, multifactorial inflammatory disease of the pilosebaceous unit brought on by hormonal imbalance, excessive sebum production, follicular hyperkeratinization, inflammation and Cutibacterium acne. Acne patients are characterized by alteration of the lipid profile. Apolipoprotein B gene (ApoB) plays an essential role in lipoprotein biosynthesis and multiple single‐nucleotide polymorphisms (SNPs) in ApoB are associated with dyslipidemia. Aim: The aim of this study was to estimate the alteration of lipid profiles in AV, determine the genetic association with lipid profile alteration by studying the ApoB gene polymorphisms, and to identify the exact haplotypes associated with acne and lipid profile alteration. Subjects and Methods: In a case–control study consisting of 63 non‐obese acne patients and 43 healthy controls, all participants underwent biochemical, anthropological assessments, and genetic analysis for ApoB polymorphisms. Result: Our results indicate that serum ApoB and the lipid profile were higher in acne patients compared with healthy subject. The most common haplotypes in acne patients were rs562338 A/rs17240441 I/c.12669 A/rs1042034 G, whereas the most common haplotypes in healthy subjects were rs562338 G/rs17240441 D/c.12669 A/rs1042034 G. Patients with mild acne had higher serum ApoB levels p = 0.005. Also, the low‐density lipoprotein cholesterol (LDL‐C) level was higher in mild acne compared with other acne groups, with a highly significant variation of p ≤ 0.001. Conclusion: We found a significant variation between the acne group and healthy controls in serum ApoB, triglycerides, total cholesterol and LDL‐C. The most common haplotypes in acne patients are rs562338 A/, rs17240441 I/, c.12669 A/ and rs1042034 G, and there is a linkage disequilibrium between the four selected SNPs. [ABSTRACT FROM AUTHOR]

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is easily neglected in the non-obese population. TyG index (triglyceride glucose Index) and TG/HDL-c (triglyceride to high-density lipoprotein cholesterol) are new indicators to evaluate insulin resistance (IR). Fibroscan is a non-invasive way to assess hepatic steatosis [by control attenuation parameters (CAP)] and fibrosis [by liver stiffness measurement (LSM)].The purpose of this study was to explore the correlation of TyG and its combination with obesity indicators [TyG-waist circumference (WC), TyG-body mass index (BMI)] and TG/HDL-c with CAP and LSM. Method One thousand seven hundred seventy-six adults (age ≥ 20 years, BMI

Objective Regular users of hormonal contraceptive pills show marked heterogeneity in metabolic effects with variations in compositions. This might be due to choice of outcome variables for comparison. Total cholesterol-high-density lipoprotein ratio (TC/HDL) discordance with low-density lipoprotein (LDL-C) has now become an established marker of future risk for atherosclerotic cardiovascular disease and stable to variations in user. Methods The present study was a randomized controlled trial to compare prevalence of TC/HDL and LDL discordance among non-obese women with polycystic ovarian syndrome (PCOS) treated with hormonal pills. Women were randomized into three arms, two arms received ultra-low dose pills (Ethinylestradiol [EE] 20 μg with drosperinone 3 mg or EE 15 μg with gestodene 60 μg) and one arm received low dose pill (EE 30 μg with desogestrel 150 μg). The role of baseline participant features and pill composition on discordance was determined. Results Discordance was observed in more than a quarter of the participants before intervention. After 1 year of treatment, less than a fifth of the participants were discordant. Ultralow-dose pill users had lower discordance, LDL, and TC than low-dose pill users after 1 year of treatment. The random forest, a non-linear classifier, showed the highest accuracy in predicting discordance. The baseline Parameters with the maximal impact on the occurrence of discordance were triglyceride, homeostatic model assessment for insulin resistance, body mass index, and high density lipoprotein. Conclusion Non-obese PCOS women on ultra-low dose pill have a lower risk of acquiring future atherosclerotic cardiovascular disease.

Background/Aims The frequency and details of nonalcoholic fatty liver disease (NAFLD) complications in patients with inflammatory bowel disease (IBD) remain unclear. This study aimed to clarify characteristics of NAFLD in patients with IBD. Methods We retrospectively identified and enrolled patients with IBD diagnosed with or without NAFLD by undergoing abdominal computed tomography (CT) at our institution between 2005 and 2020. The primary endpoint was the complication rate of NAFLD in patients with IBD. Secondary endpoints were the clinical characteristics of nonobese patients with IBD and comorbid NAFLD and their association with nutritional and inflammatory parameters. Results Twenty-one (21.9%) of 96 eligible patients with IBD also had NAFLD. In nonobese patients (defined as patients with a body mass index

Introduction: It is little known whether hyperlipidemia alone has adverse effects on the outcome of in vitro fertilization (IVF) in patients with polycystic ovarian syndrome (PCOS). Methods: The PCOS patients with body mass index (BMI) < 30 kg/m² were performed IVF or intracytoplasmic sperm injection treatment, including 208 fresh cycles and 127 frozen embryo transfer (FET) cycles. All the patients were divided into hyperlipidemia and control groups, and embryo quality and pregnancy outcomes between the two groups were compared. Results: In the fresh cycles, total gonadotropin dosage in the control group was significantly lower than that in the hyperlipidemia group, and serum estradiol levels on trigger day were reversed (P < 0.05). The embryo fragment score was positively correlated with serum low-density lipoprotein level (r = 0.06, P < 0.05) and negatively with serum high-density lipoprotein (HDL) and lipoprotein A levels (r = -0.489 and -0.085, P < 0.01). Logistic regression analysis found that HDL was beneficial for clinical pregnancy (OR = 0.355, 95% CI: 0.135-0.938, P < 0.05). In the FET cycles, there were no differences in pulse index, systolic/diastolic ratio and serum estradiol and progesterone levels between the two groups, but resistance index in the hyperlipidemia group was significantly higher than that in the control group (P < 0.05). Conclusion: Hyperlipidemia may increase the dosage of gonadotropin and have adverse effect on the embryo quality, endometrial receptivity, and clinical outcomes of lean PCOS patients. It is recommended that the non-obese patients with hyperlipidemia and PCOS perform lipid-lowering treatment before undergoing embryo transfer. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is easily neglected in the non-obese population. TyG index (triglyceride glucose Index) and TG/HDL-c (triglyceride to high-density lipoprotein cholesterol) are new indicators to evaluate insulin resistance (IR). Fibroscan is a non-invasive way to assess hepatic steatosis [by control attenuation parameters (CAP)] and fibrosis [by liver stiffness measurement (LSM)].The purpose of this study was to explore the correlation of TyG and its combination with obesity indicators [TyG-waist circumference (WC), TyG-body mass index (BMI)] and TG/HDL-c with CAP and LSM. Method: One thousand seven hundred seventy-six adults (age ≥ 20 years, BMI < 30 kg/m2) in the National Health and Nutrition Examination Survey (NHANES) 2017–2018 were included. The correlations of CAP and LSM to the indexes were assessed by generalized linear models.. Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic capability of the indicators on NAFLD and liver stiffness. Results: Survey-weighted percentage of NAFLD in non-obese was 38.6%. In the fully adjusted models, there were positive associations of TyG, TyG-BMI, TyG-WC and TG/HDL-c to CAP, with the βs of 24.810, 0.704, 0.29 and 2.983 (all p < 0.05), respectively. There were positive associations of TyG, TyG-BMI, TyG-WC, and TG/HDL-c to NAFLD, with ORs of 3.387, 1.03, 1.010 and 1.281 ((all p < 0.05)).The positive association was detected for TG/HDL-c and TyG-WC and LSM with βs of 0.057 and 0.004(p = 0.021 and p = 0.003).TyG-WC were positively associated with liver stiffness with OR of 1.006(95%CI = 1.002, 1.012). Furthermore, the TyG-WC had the strongest diagnostic capability (ROC = 0.806; 95%CI: 0.785–0.826) on NAFLD in non-obese participants, with a specificity of 0.737 and sensitivity of 0.746. Conclusion: In US non-obese population, the TyG, TyG-BMI, TyG-WC, and TG/HDL-c are positively correlated with CAP and NAFLD. TyG-WC has clinical importance in identifying NAFLD in the non-obese population. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by the accumulation of excessive fat in the liver, which can lead to fibrosis and has an increasing prevalence. NAFLD requires non-invasive diagnostic biomarkers. While typically observed in overweight individuals, it can also occur in non-obese/non-overweight individuals. Comparative studies on non-obese NAFLD patients are scarce. This study aimed to conduct a using liquid chromatography-high resolution mass spectrometry (LC-MS/MS)-based metabolic profiling of non-obese NAFLD patients and healthy controls. The patient group consisted of 27 individuals with NAFLD, while the healthy control group included 39 individuals. Both groups were between 18 and 40 years old, had a BMI of less than 25 and had alcohol consumption less than 20 g/week for men and 10 g/week for women. Serum samples were collected and analyzed using LC-MS/MS. The data were analyzed using the TidyMass and MetaboAnalyst. The LC-MS/MS analyses detected significant changes in D-amino acid metabolism, vitamin B6 metabolism, apoptosis, mTOR signaling pathway, lysine degradation, and phenylalanine metabolism pathways in non-obese NAFLD patients. Significant changes were also observed in the metabolites D-pantothenic acid, hypoxanthine, citric acid, citramalic acid, L-phenylalanine, glutamine, and histamine-trifluoromethyl-toluidide, β-hydroxymyristic acid, DL-Lactic acid, and 3-methyl-2-oxopentanoic. Overall, the study provides valuable insights into the metabolic changes associated with non-obese NAFLD patients and can contribute to the development of non-invasive diagnostic biomarkers for NAFLD. This study sheds light on the metabolic changes in non-obese NAFLD patients. Further research is needed to better understand the metabolic changes associated with NAFLD and to develop effective treatment options. [ABSTRACT FROM AUTHOR]

Background: Misperceptions about obesity is common among adolescents. Adolescents who overestimate their body size tend to indulge in extreme weight control behaviors. However, little is known about the factors involved in the adoption of extreme weight control behavior (EWCB) by non-obese adolescents who are mistaken for being overweight. This study identified factors associated with unhealthy behaviors among normal/underweight high school students who overestimate their body image and attempt to lose weight. Design: A secondary analysis of nationally representative data from the Korea Youth Risk Behavior Survey focused on adolescents who attended vocational and academically oriented high schools. Methods: The analysis included data from 4,286 non-obese respondents (15–18 years) who overestimated their body weight. Of them, 2,887 were girls (66.5%), while 1,399 were boys (33.5%). Multiple logistic regression was used to investigate risk factors for EWCB by sex. A statistical analysis reflecting strata, clusters, and weights of the complex sampling design was adopted. Results: Of the respondents, 674 (23.3%) girls and 162 (11.5%) boys reported EWCB. For both sexes, vocational high school attendance and depression were significantly influenced by EWCB. EWCB was linked to perceived stress in girls and living in a big city in boys. Conclusions: The findings suggest the importance of providing quality health education, including that for non-obese adolescents, in school obesity prevention programs along with the expansion of tailored intervention programs based on sex, following a consideration of the characteristics of high schools as well as individuals. [ABSTRACT FROM AUTHOR]

Abstract Aim Obesity is linked to cardiometabolic diseases, however non-obese individuals are also at risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). White adipose tissue (WAT) is known to play a role in both T2D and CVD, but the contribution of WAT inflammatory status especially in non-obese patients with cardiometabolic diseases is less understood. Therefore, we aimed to find associations between WAT inflammatory status and cardiometabolic diseases in non-obese individuals. Methods In a population-based cohort containing non-obese healthy (n = 17), T2D (n = 16), CVD (n = 18), T2D + CVD (n = 19) individuals, seventeen different cytokines were measured in WAT and in circulation. In addition, 13-color flow cytometry profiling was employed to phenotype the immune cells. Human T cell line (Jurkat T cells) was stimulated by rCCL18, and conditioned media (CM) was added to the in vitro cultures of human adipocytes. Lipolysis was measured by glycerol release. Blocking antibodies against IFN-γ and TGF-β were used in vitro to prove a role for these cytokines in CCL18-T-cell-adipocyte lipolysis regulation axis. Results In CVD, T2D and CVD + T2D groups, CCL18 and CD4+ T cells were upregulated significantly compared to healthy controls. WAT CCL18 secretion correlated with the amounts of WAT CD4+ T cells, which also highly expressed CCL18 receptors suggesting that WAT CD4+ T cells are responders to this chemokine. While direct addition of rCCL18 to mature adipocytes did not alter the adipocyte lipolysis, CM from CCL18-treated T cells increased glycerol release in in vitro cultures of adipocytes. IFN-γ and TGF-β secretion was significantly induced in CM obtained from T cells treated with CCL18. Blocking these cytokines in CM, prevented CM-induced upregulation of adipocyte lipolysis. Conclusion We suggest that in T2D and CVD, increased production of CCL18 recruits and activates CD4+ T cells to secrete IFN-γ and TGF-β. This, in turn, promotes adipocyte lipolysis – a possible risk factor for cardiometabolic diseases.

Background: This study aimed to perform a meta-analysis regarding the mid-long-term effect (≥ 2-year follow-up) of metabolic surgery on T2DM in non-obese patients. Methods: PubMed, EMBASE and CENTRAL databases were searched for clinical studies from inception to March 2023. Stata 12.0 was used for data aggregation. Sensitivity, subgroup, and meta-regression analyses were performed when feasible. Results: This meta-analysis included 18 articles involving 548 patients. A pooled rate of 47.5% of T2DM remission was found after metabolic surgery. To be more specific, 83.5% was obtained for hemoglobin A1c (HbA1c) < 7.0%, 45.1% for HbA1c < 6.5%, and 40.4% for HbA1c < 6.0%. Subgroup analysis showed that one-anastomosis gastric bypass (OAGB) had a higher remission rate (93.9%) than other surgeries. Studies conducted in America had a higher remission rate (61.4%) than in Asia (43.6%). Meta-regression analysis displayed that publication year, number of patients, study design, preoperative age, BMI, and quality assessment score were not significantly associated with T2DM remission rate. Additionally, metabolic surgery could result in significant reductions in BMI (-4.133 kg/m2), weight (-9.874 kg), HbA1c (-1.939%), fasting blood glucose, fasting C-peptide, and fasting insulin. However, metabolic surgery seemed to have poorer glycemic control in non-obese than obese T2DM patients. Conclusion: A moderate mid-long-term effect of T2DM remission was observed after metabolic surgery in non-obese patients. However, we still need more prospective multi-institutional studies using the same definitions for diabetes and the same surgical technique for the surgery. Without this, the exact role of bariatric surgery in non-obese patients is unanswered. [ABSTRACT FROM AUTHOR]

A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and gut microbiota before and after 6-day HCHFD consisting of a regular diet plus a 45% energy excess with dairy fat supplementation. We evaluated tissue-specific insulin sensitivity and metabolic clearance rate of insulin (MCRI) using a two-step hyperinsulinemic euglycemic clamp, glucose tolerance using the glucose tolerance test, and measured ectopic fat in muscle and the liver using ¹H-magnetic resonance spectroscopy. The primary outcome of this study was insulin sensitivity measured by the clamp study. The secondary/exploratory outcomes were other metabolic changes. After HCHFD, levels of circulating lipopolysaccharide binding protein (LBP), a marker of endotoxemia, increased by 14%. In addition, intramyocellular lipid levels in the tibialis anterior and soleus and intrahepatic lipid levels increased by 47%, 31%, and 200%, respectively. Insulin sensitivity decreased by 4% in muscle and 8% in liver. However, even with reduced insulin sensitivity, glucose metabolism was maintained by increased serum insulin concentrations due to lower MCRI and higher endogenous insulin secretion during the clamp. Glucose levels during the meal tolerance test were comparable before and after HCHFD. In conclusion, short-term HCHFD impaired insulin sensitivity in the muscle and livers of non-obese Japanese men with increased LBP and ectopic fat accumulation. Elevated insulin levels from modulated insulin secretion and clearance might contribute to the maintenance of normal glucose metabolism during the clamp and meal tolerance test. [ABSTRACT FROM AUTHOR]

Abstract Background A cross-sectional association between the combination indicator of high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyl transferase (GGT) and fatty liver has been described in several recent studies, and this study aims to further evaluate the longitudinal relationship between the ratio of GGT to HDL-C (GGT/HDL-C ratio) and nonalcoholic fatty liver disease (NAFLD). Methods This cohort study included 12,126 individuals without NAFLD at baseline, followed prospectively for 5 years, and the endpoint of interest was new-onset NAFLD. The relationship of the GGT/HDL-C ratio with new-onset NAFLD and the shape of the association was assessed by Cox regression models and restricted cubic spline (RCS) regression, respectively. Time-dependent receiver operator characteristics (ROC) curves were constructed to evaluate the predictive value of GGT, HDL-C, GGT/HDL-C ratio and BMI for the occurrence of NAFLD at different time points in the future. Results The prevalence of NAFLD was 72.46/1000 person-years during the 5-year follow-up period. Results of multivariate Cox regression analysis showed a positive association of the GGT/HDL-C ratio with new-onset NAFLD after adequate adjustment of the related confounding factors, and the degree of correlation was slightly higher than that of GGT, and further subgroup analysis found that this association was more significant in the population with elevated systolic blood pressure (SBP). In addition, we also found a nonlinear relationship of the GGT/HDL-C ratio with the risk of new-onset NAFLD using the RCS regression, where the saturation threshold was about 31.79 U/mmol. Time-dependent ROC analysis results showed that the GGT/HDL-C ratio was increasingly valuable in predicting NAFLD over time, and was better than HDL-C in predicting NAFLD in the early stage (1–3 years), but was not superior to BMI and GGT. Conclusions In this large longitudinal cohort study based on a Chinese population, our results supported that the GGT/HDL-C ratio was positively and nonlinearly associated with the risk of new-onset NAFLD in a non-obese population. In the assessment of future NAFLD risk, the GGT/HDL-C ratio was slightly better than GGT alone; However, the GGT/HDL-C ratio did not appear to have a significant advantage over GGT and BMI alone in predicting NAFLD.

Background and purpose: The association between fatty liver and fracture risk has not been firmly established. In this study, we investigated the relationship between the fatty liver index (FLI) and the incidence of fractures among individuals =50 years of age, using a nationwide population-based cohort. Methods: Data from the Korean National Health Insurance System between January 2009 and December 2019 were analyzed using the Cox proportional hazards model. Fatty liver status was defined using FLI. Newly diagnosed fractures were identified based on insurance claim data. Results: Among the 3,384,457 individuals who met our inclusion criteria over the study period, 444,203 cases of incident fractures were identified over a median follow-up of 10.3 years. On multivariate analysis, the risk of fracture was significantly higher among individuals with a higher FLI score compared to those with an FLI<30, with adjusted hazard ratio [aHR] and 95% confidence interval [CI] as follows: FLI 30-59 group, aHR 1.04 and 95% CI 1.03-1.05; and FLI =60 group, aHR 1.12 and 95% CI 1.10-1.13. A higher FLI was associated with a greater risk of hip (aHR 1.23 and 1.52 for the FLI 30-59 and FLI =60 group, respectively) and vertebral fracture (aHR 1.08 and 1.16 for the FLI 30-59 and FLI=60 group, respectively). The association between the risk for fracture and FLI =60 was prominent for non-obese than obese individuals (aHR 1.25 and 95% CI, 1.22-1.27 versus 1.06 and 1.05-1.08, respectively). Conclusions: A high FLI is associated with an increased risk of hip and vertebral fractures among individuals =50 years of age, suggestive of an association between a higher FLI and osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20–30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals. [ABSTRACT FROM AUTHOR]

Aim: Obesity is linked to cardiometabolic diseases, however non-obese individuals are also at risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). White adipose tissue (WAT) is known to play a role in both T2D and CVD, but the contribution of WAT inflammatory status especially in non-obese patients with cardiometabolic diseases is less understood. Therefore, we aimed to find associations between WAT inflammatory status and cardiometabolic diseases in non-obese individuals. Methods: In a population-based cohort containing non-obese healthy (n = 17), T2D (n = 16), CVD (n = 18), T2D + CVD (n = 19) individuals, seventeen different cytokines were measured in WAT and in circulation. In addition, 13-color flow cytometry profiling was employed to phenotype the immune cells. Human T cell line (Jurkat T cells) was stimulated by rCCL18, and conditioned media (CM) was added to the in vitro cultures of human adipocytes. Lipolysis was measured by glycerol release. Blocking antibodies against IFN-γ and TGF-β were used in vitro to prove a role for these cytokines in CCL18-T-cell-adipocyte lipolysis regulation axis. Results: In CVD, T2D and CVD + T2D groups, CCL18 and CD4+ T cells were upregulated significantly compared to healthy controls. WAT CCL18 secretion correlated with the amounts of WAT CD4+ T cells, which also highly expressed CCL18 receptors suggesting that WAT CD4+ T cells are responders to this chemokine. While direct addition of rCCL18 to mature adipocytes did not alter the adipocyte lipolysis, CM from CCL18-treated T cells increased glycerol release in in vitro cultures of adipocytes. IFN-γ and TGF-β secretion was significantly induced in CM obtained from T cells treated with CCL18. Blocking these cytokines in CM, prevented CM-induced upregulation of adipocyte lipolysis. Conclusion: We suggest that in T2D and CVD, increased production of CCL18 recruits and activates CD4+ T cells to secrete IFN-γ and TGF-β. This, in turn, promotes adipocyte lipolysis – a possible risk factor for cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to evaluate the effect of ten proinflammatory cytokines in GCF of participants with raised body mass index (BMI) compared to nonobese subjects undergoing fixed orthodontic treatment. PATIENTS AND METHODS: In the cross-sectional cohort, subjects were shortlisted through the purposive sampling method with the same age and gender and similar characteristics (cohort). For inclusion and exclusion, predefined criteria were followed. In all included participants obese and non-obese collection of GCF was made from mandibular canine to canine. Identification of inflammatory mediators (MPO and CRP) leptin, adiponectin, and resistin (pg/mL). Bone remodeling biomarkers RANKL (pg/mL) and tissue remodeling biomarkers MMP8, MMP9, TIMP1, and MMP8/TIMP1, MMP9/TIMP1 ratio were collected and blinded by the investigator. Normal distribution of data i.e., age, BMI, the flow rate of GCF, indices plaque and gingival, and uWMS were compared using a t-test. Non-normality biomarker data were evaluated using Mann-Whitney U-test. To assess the relationship between the concentration of GCF biomarkers and plaque and gingival indices Pearson and Spearman correlation coefficients were used. RESULTS: The total number of participants included was 44. In the obese and non-obese groups, the male/female ratio was the same i.e., (n=11 each). The mean age of participants in the obese group was 25.7±1.55 years, whereas the non-obese group was 26.1±1.29 years. In obese the mean BMI was 33.6±2.1 kg/m2 whereas in non-obese 22.9±1.9 kg/m2 (p<0.02). Among the levels of biomarkers adiponectin (p<0.006) and leptin (p<0.028) demonstrated a significant difference between obese and non-obese participants. Also, a significant difference was noted between obese and non-obese in tissue remodeling biomarker MMP9 (p<0.03). CONCLUSIONS: A surge in the level of the biomarkers, i.e., MMP9, leptin, and adiponectin in the gingival crevicular fluid is found in obese undergoing fixed orthodontic treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: Lean patients with non-alcoholic fatty liver disease (NAFLD) represent 10–20% of the affected population and may have heterogeneous drivers of disease. We have recently proposed the evaluation of patients with lean NAFLD without visceral adiposity for rare monogenic drivers of disease. Here, we aimed to validate this framework in a well-characterised cohort of patients with biopsy-proven NAFLD by performing whole exome sequencing. Methods: This prospective study included 124 patients with biopsy-proven NAFLD and paired liver biopsies who underwent standardised research visits including advanced magnetic resonance imaging (MRI) assessment of liver fat and stiffness. Results: Six patients with lean NAFLD were identified and underwent whole exome sequencing. Two lean patients (33%) were identified to have monogenic disorders. The lean patients with monogenic disorders had similar age, and anthropometric and MRI characteristics to lean patients without a monogenic disorder. Patient 1 harbours a rare homozygous pathogenic mutation in ALDOB (aldolase B) and was diagnosed with hereditary fructose intolerance. Patient 2 harbours a rare heterozygous mutation in apolipoprotein B (APOB). The pathogenicity of this APOB variant (p.Val1856CysfsTer2) was further validated in the UK Biobank and associated with lower circulating APOB levels (beta = -0.51 g/L, 95% CI -0.65 to -0.36 g/L, p = 1.4 × 10-11) and higher liver fat on MRI (beta = +10.4%, 95% CI 4.3–16.5%, p = 8.8 × 10-4). Hence, patient 2 was diagnosed with heterozygous familial hypobetalipoproteinaemia. Conclusions: In this cohort of well-characterised patients with lean NAFLD without visceral adiposity, 33% (2/6) had rare monogenic drivers of disease, highlighting the importance of genomic analysis in this NAFLD subtype. Impact and Implications: Although most people with non-alcoholic fatty liver disease (NAFLD) are overweight or obese, a subset are lean and may have unique genetic mutations that cause their fatty liver disease. We show that 33% of study participants with NAFLD who were lean harboured unique mutations that cause their fatty liver, and that these mutations had effects beyond the liver. This study demonstrates the value of genetic assessment of NAFLD in lean individuals to identify distinct subtypes of disease.

We performed a meta‐analysis to evaluate the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer. A systematic literature search up to March 2022 was performed and 2247 subjects with possibly curative surgery for colorectal cancer at the baseline of the studies; 2889 of them were obese, and 9358 were non‐obese. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer using the dichotomous or contentious methods with a random or fixed‐effect model. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery (OR, 1.87; 95% CI, 1.62‐2.15, P <.001), and higher mortality (OR, 1.58; 95% CI, 1.07‐2.32, P =.02) in subjects with possibly curative surgery for colorectal cancer compared with non‐obese. However, obese did not show any significant difference in postoperative hospital stay (MD, 0.81; 95% CI, −0.030 to 1.92, P =.15) compared with non‐obese in subjects with possibly curative surgery for colorectal cancer. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery, higher mortality, and no significant difference in postoperative hospital stay compared with non‐obese in subjects with possibly curative surgery for colorectal cancer. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons. [ABSTRACT FROM AUTHOR]

Background: A cross-sectional association between the combination indicator of high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyl transferase (GGT) and fatty liver has been described in several recent studies, and this study aims to further evaluate the longitudinal relationship between the ratio of GGT to HDL-C (GGT/HDL-C ratio) and nonalcoholic fatty liver disease (NAFLD).Methods: This cohort study included 12,126 individuals without NAFLD at baseline, followed prospectively for 5 years, and the endpoint of interest was new-onset NAFLD. The relationship of the GGT/HDL-C ratio with new-onset NAFLD and the shape of the association was assessed by Cox regression models and restricted cubic spline (RCS) regression, respectively. Time-dependent receiver operator characteristics (ROC) curves were constructed to evaluate the predictive value of GGT, HDL-C, GGT/HDL-C ratio and BMI for the occurrence of NAFLD at different time points in the future.Results: The prevalence of NAFLD was 72.46/1000 person-years during the 5-year follow-up period. Results of multivariate Cox regression analysis showed a positive association of the GGT/HDL-C ratio with new-onset NAFLD after adequate adjustment of the related confounding factors, and the degree of correlation was slightly higher than that of GGT, and further subgroup analysis found that this association was more significant in the population with elevated systolic blood pressure (SBP). In addition, we also found a nonlinear relationship of the GGT/HDL-C ratio with the risk of new-onset NAFLD using the RCS regression, where the saturation threshold was about 31.79 U/mmol. Time-dependent ROC analysis results showed that the GGT/HDL-C ratio was increasingly valuable in predicting NAFLD over time, and was better than HDL-C in predicting NAFLD in the early stage (1-3 years), but was not superior to BMI and GGT.Conclusions: In this large longitudinal cohort study based on a Chinese population, our results supported that the GGT/HDL-C ratio was positively and nonlinearly associated with the risk of new-onset NAFLD in a non-obese population. In the assessment of future NAFLD risk, the GGT/HDL-C ratio was slightly better than GGT alone; However, the GGT/HDL-C ratio did not appear to have a significant advantage over GGT and BMI alone in predicting NAFLD. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies have demonstrated the presence of associations between metabolic syndrome and the onset of nonalcoholic fatty liver disease (NAFLD). Metabolic syndrome, in turn, has been found to be linked to high serum uric acid to HDL-cholesterol ratios (UHR). However, the relationship between UHR values and the occurrence of NAFLD in non-obese individuals remains unknown. The present study aimed to examine the possible correlation between UHR values and NAFLD onset among a non-obese Chinese population without dyslipidemia, as well as comparing the predictive value of UHR versus other NAFLD onset predictors. Methods A total of 9837 non-obese patients, with normal blood lipid levels, were included in a 5-year retrospective cohort study, and the onset of NAFLD in these patients was diagnosed by liver ultrasound. Results Out of the 9837 patients, 855 were diagnosed with NAFLD during the 5-year follow-up period, for an overall total prevalence of 8.7% at the end of the study period. Across quintiles 1, 2, 3, 4 and 5 of UHR (respectively, ratios of ≤ 120.88, 120.89–154.01, 154.02–189.91, 189.92–240.46, and ≥ 240.47), the prevalence of NAFLD among the patients increased from 2.4%, 5%, 7.9%, 10.3%, and 17.8%, respectively. After adjustments for age, gender, liver and kidney functional markers, as well as metabolic indicators, multivariate Cox proportional hazard regression analysis demonstrated that the hazard ratio (HR) was the highest in quintile 5, at 1.76 (1.12–2.75), and the lowest in quintile 1. The area under the curve (AUC) for UHR (0.690) was higher than that for serum uric acid (UA, 0.666) and HDL-C (0.636), suggesting the predictive ability of UHR for NAFLD onset was better than either alone. This finding was further supported by the presence of an independent association between UHR and NAFLD, even within the normal range of UA and HDL-C; the HR (95% confidence interval, CI) for NAFLD was 1.002 (1.000–1.004). Compared with other significant predictors, AUC for UHR (0.67) was similar to that of low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C, 0.68), non-high-density lipoprotein cholesterol (NHDL-C)/HDL-C (0.68) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratios (0.7), and was higher than that of LDL-C (0.63), remnant cholesterol (RC,0.59), and albumin (ALB)/alkaline phosphatase (ALP) ratio (0.61). The sensitivity of UHR (71%) was the highest among all indicators. In the subgroup with ALT 40U/L, UHR was able to predict the occurrence of NAFLD (AUC = 0.61, p = 0.007), which was not the case for RC (P = 0.441), ALB/ALP (P = 0.419), and ALT/AST (P = 0.159). Conclusions UHR serve as an inexpensive and reliable predictor of NAFLD onset in non-obese Chinese people with normal blood lipid levels, allowing for identification of individuals at high risk for NAFLD.

Abstract Background Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5–8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points. Results Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment. Conclusions These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions that are characterized by excess accumulation of fat in the liver, and is diagnosed after exclusion of significant alcohol intake and other causes of chronic liver disease. In the majority of cases, NAFLD is associated with overnutrition and obesity, although it may be also found in lean or non-obese individuals. It has been estimated that 19.2% of NAFLD patients are lean and 40.8% are non-obese. The proportion of patients with more severe liver disease and the incidence of all-cause mortality, liver-related mortality, and cardiovascular mortality among non-obese and obese NAFLD patients varies across studies and may be confounded by selection bias, underestimation of alcohol intake, and unaccounted weight changes over time. Genetic factors may have a greater effect towards the development of NAFLD in lean or non-obese individuals, but the effect may be less pronounced in the presence of strong environmental factors, such as poor dietary choices and a sedentary lifestyle, as body mass index increases in the obese state. Overall, non-invasive tests, such as the Fibrosis-4 index, NAFLD fibrosis score, and liver stiffness measurement, perform better in lean or non-obese patients compared to obese patients. Lifestyle intervention works in non-obese patients, and less amount of weight loss may be required to achieve similar results compared to obese patients. Pharmacological therapy in non-obese NAFLD patients may require special consideration and a different approach compared to obese patients.

Background and aims: it is unclear whether male hypogonadism is ascribable to the diabetic state per se, or because of other factors, such as obesity or age. We aimed to investigate the prevalence and identify the predictors for testosterone deficiency among non-obese type 2 diabetic males. Methods: This cross-sectional study was conducted on 95 nonobese type 2 diabetic males with BMI below 30. We evaluated the total testosterone (TT) levels to determine prevalence and risk factors of testosterone deficiency. Serum TT ≤ 300 ng/dl defined testosterone deficiency. Results: The prevalence of testosterone deficiency was 29.1%. Testosterone deficient patients had statistically significantly higher visceral adiposity index (VAI), waist, and triglyceride in comparison with normal testosterone patients. TT level correlated with VAI, waist, BMI, LH, and age. VAI was the only significant predictor of TT levels even after adjustment for age and BMI in regression analysis. Furthermore, VAI was a statistically significant risk factor for testosterone deficiency in binary logistic analysis. Conclusions: testosterone deficient non-obese type 2 diabetic male patients had elevated VAI, waist, and triglyceride. Moreover, elevated VAI was a risk factor for testosterone deficiency. VAI could be an easily applicable and reliable index for the evaluation and prediction in type 2 non-obese diabetic males.

Background and aims: it is unclear whether male hypogonadism is ascribable to the diabetic state per se, or because of other factors, such as obesity or age. We aimed to investigate the prevalence and identify the predictors for testosterone deficiency among non-obese type 2 diabetic males. Methods: This cross-sectional study was conducted on 95 nonobese type 2 diabetic males with BMI below 30. We evaluated the total testosterone (TT) levels to determine prevalence and risk factors of testosterone deficiency. Serum TT = 300 ng/dl defined testosterone deficiency. Results: The prevalence of testosterone deficiency was 29.1%. Testosterone deficient patients had statistically significantly higher visceral adiposity index (VAI), waist, and triglyceride in comparison with normal testosterone patients. TT level correlated with VAI, waist, BMI, LH, and age. VAI was the only significant predictor of TT levels even after adjustment for age and BMI in regression analysis. Furthermore, VAI was a statistically significant risk factor for testosterone deficiency in binary logistic analysis. Conclusions: testosterone deficient non-obese type 2 diabetic male patients had elevated VAI, waist, and triglyceride. Moreover, elevated VAI was a risk factor for testosterone deficiency. VAI could be an easily applicable and reliable index for the evaluation and prediction in type 2 non-obese diabetic males. [ABSTRACT FROM AUTHOR]

Background and Objectives: The problem of metabolic syndrome among non-obese older people is often ignored. This study examines the risk factors for metabolic syndrome in non-obese older people in Indonesia. We analyzed information collected from 3323 non-obese older respondents interviewed in the 2018 Basic Health Research program. Methods and Study Design: The outcome variable was the metabolic syndrome consisting of three components: high lipid profile, diabetes mellitus, and hypertension. The potential predictors analyzed were socio-demographic and behavioral factors consisting of psychomotor (cigarette smoking + physical activity) and dietary behavior (consumption of fat + fruit/vegetable). Multinomial logistic regression analysis was employed to assess metabolic syndrome risk factors in non-obese older people. Results: We found that the proportion of non-obese older people in Indonesia with metabolic syndrome was 83.8% (95%CI: 82.4-85.2%). The odds of developing 2-3 components of metabolic syndrome increased in respondents from rural areas (aOR=1.26, p=0.033) and those with moderate psychomotor behavior problems (current smoker/ex-smoker with sufficient physical activity) (aOR=1.48, p=0.002). Conclusions: Health promotion activities are vital to improve awareness and promote healthy behaviors, specifically for those living in rural areas and smoking cigarettes. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatohepatitis (MASH) in lean individuals represents a distinctive subset of MASH. Current pharmacotherapies, for MASH as demonstrated in clinical trials, predominantly target obese patients with limited consideration for lean MASH. We aimed to systematically review the literature on the pharmacotherapy of lean MASH. We searched standard medical databases, such as PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov to identify eligible studies published in English up to 31 December 2023 regarding the effect of pharmacological interventions in individuals with lean MASH. We have summarized the role of various drug classes including peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, vitamin E, farnesoid X receptor agonists, selective thyroid hormone receptor-β agonists, and selective cholesterol absorption inhibitors. Consequently, lifestyle interventions, encompassing dietary modifications, exercise, and weight loss particularly directed at visceral obesity or achieving a reduction in body weight are recommended for all non-obese individuals with MASH. A highlight on the only available treatment recommendation for lean MASH is also presented. The available evidence regarding the efficacy of various drugs for the treatment of lean MASH is limited. Conclusive evidence is warranted from clinical trials exclusively involving lean individuals with MASH.

Xin-Tian Cai,1,2,&ast; Qing Zhu,1,2,&ast; Sha-Sha Liu,2 Meng-Ru Wang,2 Ting Wu,2 Jing Hong,2 Jun-Li Hu,2 Nanfang Li1,2 1Graduate School, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang LiGraduate School, Xinjiang Medical University; Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Hypertension Institute, National Health Committee Key Laboratory of Hypertension Clinical Research, Key Laboratory of Xinjiang Uygur Autonomous Region, Xinjiang Clinical Medical Research Center for Hypertension Diseases, Urumqi, Xinjiang, People’s Republic of ChinaEmail lnanfang2016@sina.comPurpose: The metabolic score for insulin resistance (METS-IR) index is an emerging surrogate predictor of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the METS-IR index and the risk of T2DM in non-obese Japanese adults.Methods: A total of 12,290 non-obese participants were selected from the NAGALA prospective cohort study conducted from 2004 to 2015. Cox proportional hazards models were used to assess the association between the baseline METS-IR index and risk of T2DM. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. Results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During a median follow-up of 2050 days, 176 (1.43%) incident T2DM occurred. The fully adjusted HR (95% CI) for the incidence of T2DM in non-obese adults was 1.17 (HR=1.17, 95% CI: 1.09– 1.27, P< 0.001) for every 1-unit increase in the METS-IR index. The risk of developing T2DM increased with the quartile of change in the METS-IR index, after adjustment for multiple potential confounding, the HRs for the Q4 group versus the Q1 group was 4.01 (95% CI, 1.39– 11.57). Generalized additive models also showed a cumulative increase in the risk of T2DM with increasing the METS-IR index. Time-dependent receiver operating curve suggested helpful discriminative power of the METS-IR index for T2DM. The C-statistics by the clinical risk factors significantly improve with the addition of the METS-IR index (from 0.862 to 0.875, P = 0.035); the discriminatory power and risk reclassification also appeared to be substantially better, with the category-free NRI of 0.216, and the IDI of 0.011.Conclusion: The METS-IR index was a significant and independent predictor for future T2DM development in non-obese adults. The METS-IR index may have clinical significance in identifying groups at high risk of T2DM.Keywords: metabolic score for insulin resistance index, type 2 diabetes mellitus, non-obese, population-based cohort study

The homeostasis model assessment of insulin resistance (HOMA-IR) is widely used in clinical practice to estimate insulin resistance. In particular, magnesium (Mg) is an extensively studied mineral that has been shown to function in the management of hyperglycemia and insulin resistance (IR) action. The pathophysiology of IR in non-obese patients has not been clearly demonstrated. From this point of view, we aimed to investigate the relationship between serum Mg level and IR in non-obese patients. We analyzed 957 patients who are not obese and estimated glomerular filtration rate (e-GFR) ≥ 60 mL/min/1.73 m2. Patients were divided into two groups, with and without IR. The results of the IR detected group (HOMA-IR ≥ 2.5, n = 544) and the IR undetected group (HOMA-IR < 2.5, n = 413) were compared. The median Mg value of the patients was 1.76 [0.21] mg/dL. A statistically significant difference was observed between the two groups regarding serum Mg levels (p = 0.043). A negative correlation was found between the HOMA-IR index and serum Mg levels among patients (r = − 0.064, p = 0.049). Multivariable logistic regression analysis revealed that serum Mg level (p = 0.039, odds ratio [OR] = 0.770[95%CI: [0.917–0.989]) was independent risk factors for IR. HOMA-IR increases as the Mg level decreases in advanced ages without obesity, especially in men with low e-GFR. [ABSTRACT FROM AUTHOR]

Abstract Background The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. Methods The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. Results The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend

Yifang Li, Yanzhen Chen, Xing Tian, Shanshan Zhang, Jian Jiao Department of Gastroenterolgy & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, 130033, People’s Republic of ChinaCorrespondence: Jian JiaoDepartment of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of ChinaTel +86 13756009567Fax +86 0431-84995850Email jjian@jlu.edu.cnObjective: Non-alcoholic fatty liver disease (NAFLD), previously thought to predominantly affect obese individuals, has also been shown to occur in subjects who have a relatively normal body mass index (BMI). Due to the normal BMI, non-obese NAFLD are easily to be ignored and eventually lead to potential liver injuries.Methods: A population-based cross-sectional study was conducted on 1608 cases with normal serum alanine aminotransferase (ALT) levels who were divided into an obese group (BMI ≥ 25 kg/m2) and a non-obese group (BMI < 25 kg/m2). NAFLD was diagnosed by ultrasound and Fibro Scan examination. Non-obese populations were divided into NAFLD group (CAP ≥ 240 db/m) and non-NAFLD group (CAP < 240 db/m). The incidence of NAFLD in the obese and non-obese populations and constituent ratios of genders, age, and serum levels of triglycerides (TG), cholesterol (CHOL), and blood glucose were compared. Risk factors of NAFLD in non-obese people were analyzed by multivariate logistics regression.Results: The occurrence of NAFLD was higher in the obese group than in the non-obese group, regardless of gender (P < 0.001). In the non-obese group, the occurrence of NAFLD in female patients was lower than that in male (P=0.001). The occurrence of NAFLD increased with age, with 50– 59 years being the peak age of incidence in both male and female. The peak age of NAFLD occurrence in non-obese male patients was more delayed than that in obese male patients. BMI (OR=1.311, P=0.000) and TG (OR=2.545, P=0.000) were risk factors for NAFLD in the non-obese population.Conclusion: Compared with obese population, the incidence of NAFLD in non-obese population was relatively low and more frequently in male than in female, the peak age of NAFLD occurrence in non-obese male patients was also delayed. BMI and TG should still be controlled to avoid the occurrence of NAFLD although the BMI of such patients is normal.Keywords: obese, non-obese, non-alcoholic liver disease, gender, characteristic

Abstract Background Low-density lipoprotein to high density lipoprotein (LDL/HDL) cholesterol ratio has been reported to predict the risk of many metabolic diseases. However, the association between the LDL/HDL cholesterol ratio and nonalcoholic fatty liver disease (NAFLD) has not been established. Methods A longitudinal cohort design was adopted in this study; 9767 non-obese subjects without NAFLD were included and analyzed. The subjects were grouped according to the quintile of LDL/HDL cholesterol ratio. The cumulative incidence of NAFLD and the independent effect of the LDL/HDL cholesterol ratio on NAFLD during 5 years of follow-up were calculated using the Kaplan-Meier method and Cox proportional-hazards regression model. Results During the 5-year follow-up period, 841 subjects were diagnosed with new-onset NAFLD, and the 1-, 2-, 3-, 4-, and 5-year cumulative incidence rates of NAFLD were 1.16, 4.65, 8.33, 12.43, and 25.14%, respectively. In the multivariable-adjusted Cox proportional-hazards regression model, the LDL/HDL cholesterol ratio was significantly associated with the risk for NAFLD (HR: 1.66, 95% CI: 1.38–1.99, P trend

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20–30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.

Childhood obesity has been linked to physical and psychological comorbidities that can be carried into adulthood. A bidirectional link between body weight and the stress system appears to exist, as cortisol may affect the regulation of appetite, while adiposity can affect cortisol secretion. Among the biological tissues used to evaluate cortisol concentrations, scalp hair can provide retrospective measures. The aim of this systematic review was to investigate the difference in hair cortisol concentrations between obese and non-obese minors ≤ 19 years of age. Children and adolescents with genetic, somatic or psychiatric comorbidities were excluded. The work was conducted following the PRISMA guidelines, using prespecified search terms in the Pubmed database. The initial search yielded 56 studies, while the last step of the screening procedure concluded in 9 observational studies. Among them, the results could be characterized as inconclusive. Five of them demonstrated significantly higher hair cortisol concentrations in obese children and adolescents than normal weight subjects. On the contrary, the remaining four found no statistically significant differences in hair cortisol concentrations between obese and non-obese subjects. Different methodologies applied, and confounding factors could explain the inconsistency in the findings. Further research is needed to provide more solid results. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated the presence of associations between metabolic syndrome and the onset of nonalcoholic fatty liver disease (NAFLD). Metabolic syndrome, in turn, has been found to be linked to high serum uric acid to HDL-cholesterol ratios (UHR). However, the relationship between UHR values and the occurrence of NAFLD in non-obese individuals remains unknown. The present study aimed to examine the possible correlation between UHR values and NAFLD onset among a non-obese Chinese population without dyslipidemia, as well as comparing the predictive value of UHR versus other NAFLD onset predictors.Methods: A total of 9837 non-obese patients, with normal blood lipid levels, were included in a 5-year retrospective cohort study, and the onset of NAFLD in these patients was diagnosed by liver ultrasound.Results: Out of the 9837 patients, 855 were diagnosed with NAFLD during the 5-year follow-up period, for an overall total prevalence of 8.7% at the end of the study period. Across quintiles 1, 2, 3, 4 and 5 of UHR (respectively, ratios of ≤ 120.88, 120.89-154.01, 154.02-189.91, 189.92-240.46, and ≥ 240.47), the prevalence of NAFLD among the patients increased from 2.4%, 5%, 7.9%, 10.3%, and 17.8%, respectively. After adjustments for age, gender, liver and kidney functional markers, as well as metabolic indicators, multivariate Cox proportional hazard regression analysis demonstrated that the hazard ratio (HR) was the highest in quintile 5, at 1.76 (1.12-2.75), and the lowest in quintile 1. The area under the curve (AUC) for UHR (0.690) was higher than that for serum uric acid (UA, 0.666) and HDL-C (0.636), suggesting the predictive ability of UHR for NAFLD onset was better than either alone. This finding was further supported by the presence of an independent association between UHR and NAFLD, even within the normal range of UA and HDL-C; the HR (95% confidence interval, CI) for NAFLD was 1.002 (1.000-1.004). Compared with other significant predictors, AUC for UHR (0.67) was similar to that of low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C, 0.68), non-high-density lipoprotein cholesterol (NHDL-C)/HDL-C (0.68) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratios (0.7), and was higher than that of LDL-C (0.63), remnant cholesterol (RC,0.59), and albumin (ALB)/alkaline phosphatase (ALP) ratio (0.61). The sensitivity of UHR (71%) was the highest among all indicators. In the subgroup with ALT < 40U/L, the AUC for UHR was 0.70, which was the highest among all predictors; among ALT > 40U/L, UHR was able to predict the occurrence of NAFLD (AUC = 0.61, p = 0.007), which was not the case for RC (P = 0.441), ALB/ALP (P = 0.419), and ALT/AST (P = 0.159).Conclusions: UHR serve as an inexpensive and reliable predictor of NAFLD onset in non-obese Chinese people with normal blood lipid levels, allowing for identification of individuals at high risk for NAFLD. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS) in childhood is a complex disease primarily due both to adenotonsillar hypertrophy and pediatric obesity. Notably, inflammation has been recognized as one of the most important shared pathogenic factor between obesity and OSAS resulting in an increased cardiometabolic risk for these patients. To date, evidence is still limited in non-obese population with OSAS. We aimed to evaluate the cardiometabolic risk profile of a pediatric population of non-obese subjects affected by OSAS. A total of 128 school-aged children (mean age 9.70 ± 3.43) diagnosed with OSAS and 213 non-OSAS children (mean age 9.52 ± 3.35) as control group were enrolled. All subjects underwent a complete clinical and biochemical assessment (including white blood cell count (WBC), platelet count (PLT), mean platelet volume (MPV), % of neutrophils (NEU%), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), uric acid, fasting insulin, iron, ferritin, and transferrin levels). A significant association between inflammation markers (including WBC, PLT, MPV, NEU%, ferritin, CPR, and ESR) and OSAS was found (all p < 0.001). Children with OSAS also showed increased transaminase, glucose, uric acid, and insulin levels (all p < 0.001) compared to healthy controls.Conclusion: Taken together, these findings suggested a worse cardiometabolic profile in non-obese children with OSAS. Given the pivotal pathogenic role of inflammation both for hypoxiemia and metabolic derangements, therapeutic strategies for OSAS might also counteract the increased cardiometabolic risk of these patients, by improving their long-term quality of life.What Is Known: • Pediatric OSAS has shown a close relationship with obesity and its cardiometabolic comorbidities. • Inflammation represents the hallmark of both obesity and OSAS.What Is New: • Non obese children with OSAS presented with a worse cardiometabolic risk profile. • OSAS treatment might serve as an effective approach also for the increased cardiometabolic risk of these children. [ABSTRACT FROM AUTHOR]

Obesity is a common comorbidity of type 2 diabetes (T2D). Therefore, increased risk of fragility fractures in T2D is often confounded by the effects of obesity. This study was conducted to elucidate the mechanistic basis by which T2D alone leads to skeletal fragility. We hypothesized that obesity independent T2D would deteriorate bone's material quality by accumulating defects in the mineral matrix and undesired modifications in its organic matrix associated with increased oxidative stress and hyperglycemia. To test this hypothesis, we used 15‐week‐old male non‐obese mice with engineered muscle creatine kinase promoter/human dominant negative insulin growth factor 1 (IGF‐I) receptor (MKR) and FVB/N wild‐type (WT) controls (n = 12/group). MKR mice exhibit reduced insulin production and loss of glycemic control leading to diabetic hyperglycemia, verified by fasting blood glucose measurements (>250 mg/dL), without an increase in body weight. MKR mice showed a significant decrease in femoral radial geometry (cortical area, moment of inertia, cortical thickness, endosteal diameter, and periosteal diameter). Bone mineral density (BMD), as assessed by micro–computed tomography (μCT), remained unchanged; however, the quality of bone mineral was altered. In contrast to controls, MKR mice had significantly increased hydroxyapatite crystal thickness, measured by small‐angle X‐ray scattering, and elongated c‐axis length of the crystals evaluated by confocal Raman spectroscopy. There was an increase in changes in the organic matrix of MKR mice, associated with enhanced glycoxidation (carboxymethyl‐lysine [CML] and pentosidine) and overall glycation (fluorescent advanced glycation end products), both of which were associated with various measures of bone fragility. Moreover, increased CML formation positively correlated with elongated mineral crystal length, supporting the role of this negatively charged side chain to attract calcium ions, promote growth of hydroxyapatite, and build a physical link between mineral and collagen. Collectively, our results show, for the first time, changes in bone matrix in a non‐obese T2D model in which skeletal fragility is attributable to alterations in the mineral quality and undesired organic matrix modifications. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]