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Fenofibrate is a peroxisome proliferator-activated receptor-[alpha] (PPAR[alpha]) activator that has been clinically used to treat dyslipidemia and insulin resistance. To better understand the molecular mechanisms underlying fenofibrate action, we investigated whether fenofibrate affects serum levels of retinal-binding protein-4 (RBP4), an adipocytokine that has recently been shown to link obesity and insulin resistance. Fenofibrate treatment significantly decreased serum RBP4 levels of dyslipidemic patients, which correlated with reduced body weight and increased insulin sensitivity. To elucidate the biochemical mechanisms of fenofibrate action, we investigated the effect of fenofibrate on RBP4 expression in obese rats. Fenofibrate greatly decreased RBP4 mRNA levels in adipose tissue but not in the liver, which correlated with decreased serum RBP4 levels and increased insulin sensitivity in obese rats. Consistent with a direct effect on RBP4 expression, fenofibrate treatment significantly reduced the mRNA expression levels of RPB4 in 3T3-L1 adipocytes. Together, our results demonstrate for the first time that fenofibrate inhibits RPB4 expression in dyslipidemic human subjects and suggest that inhibition of RBP4 expression in adipocytes may provide a mechanism by which fenofibrate improves insulin sensitivity in dyslipidemic patients. insulin resistance; liver

Background and Aims: Carotid intima-media thickness (C-IMT) is an important index for evaluating subclinical atherosclerosis. Neck circumference (NC), a new anthropometric index of the upper body fat, is closely related to cardiovascular disease (CVD) and CVD risk factors. This study investigated the relationship between NC, C-IMT, and carotid plaque in a community-based cohort.Methods and Results: Participants recruited from Shanghai communities were followed up for 1.1-2.9 years. All participants underwent anthropometric and biochemical measurements. Elevated NC was defined as NC ≥ 38.5 cm and NC ≥ 34.5 cm in men and women, respectively. Elevated C-IMT, determined by ultrasound, was defined as a level higher than the 75th percentile in the study population (>0.75 mm). In total, 1189 participants without carotid plaque at baseline were included, with an average age of 59.6 ± 7.3 years. After a mean follow-up of 2.1 ± 0.2 years, 203 participants developed carotid plaques. After adjusting for various atherosclerosis risk factors, the logistic regression showed that the higher NC group had a significantly greater risk of developing carotid plaque than the lower NC group (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.12-2.14; P = 0.008). Of those without carotid plaque at follow-up, 495 participants developed elevated C-IMT. Compared to the lower NC group, the higher NC group had a significantly increased risk of elevated C-IMT (OR, 1.49; 95% CI, 1.14-1.95; P = 0.003).Conclusion: Higher NC was significantly positively correlated with the risk of carotid plaque and elevated C-IMT. [ABSTRACT FROM AUTHOR]

Objective: Visceral obesity, reflected by the amount of visceral adipose tissue (VAT), is associated with multiple chronic diseases and metabolic disorders. The visceral fat area (VFA), measured by MRI, is the 'gold standard' for diagnosis of visceral obesity. In this study, a simple model to predict VFA was constructed to facilitate the identification and monitoring of patients who are at high risk of visceral obesity. Methods: The 721 overweight and obese participants were divided into two groups according to sex, then randomly assigned to derivation and validation cohorts in a 1:2 ratio. Data from the derivation group were used to construct a multiple linear regression model; data from the validation group were used to verify the validity of the model. Results: The following prediction equations, applicable to both sexes, were developed based on age, waist circumference (WC) and neck circumference (NC) that exhibited strong correlations with the VFA: VFA=3.7×age+2.4×WC+5.5×NC-443.6 (R2 = 0.511, adjusted R2 = 0.481, for men) and VFA=2.8×age+1.7×WC+6.5×NC-367.3 (R2 = 0.442, adjusted R2 = 0.433, for women). The data demonstrated good fit for both sexes. A comparison of the predicted and actual VFA in the verification group confirmed the accuracy of the equations: for men, R2 = 0.489, adjusted R2 = 0.484 and intra-class correlation coefficient (ICC) = 0.653 (p < 0.001) and for women: R2 = 0.538, adjusted R2= 0.536 and ICC = 0.672 (p < 0.001). The actual and predicted VFAs also showed good agreement in a Bland-Altman plot, indicating the significant correlations of both equations with the actual VFA. Conclusions: Based on readily available anthropometric data, VFA prediction equations consisting of age, WC and NC were developed. The equations are robust, with good predictive power in both sexes; they provide ideal tools for the early detection of visceral obesity in Chinese overweight and obese individuals. [ABSTRACT FROM AUTHOR]

Stretchable, adhesive, and conductive hydrogels have been regarded as ideal interfacial materials for seamless and biocompatible integration with the human body. However, existing hydrogels can rarely achieve good mechanical, electrical, and adhesive properties simultaneously, as well as limited patterning/manufacturing techniques posing severe challenges to bioelectronic research and their practical applications. Herein, we develop a stretchable, adhesive, and conductive Ti3C2Tx-polyacrylic acid hydrogel by a simple pre-crosslinking method followed by successive direct ink writing 3D printing. Pre-polymerization of acrylic acid can be initiated by mechanical mixing with Ti3C2Tx nanosheet suspension, leading to the formation of viscous 3D printable ink. Secondary free radical polymerization of the ink patterns via 3D printing can achieve a stretchable, adhesive, and conductive Ti3C2Tx-polyacrylic acid hydrogel. The as-formed hydrogel exhibits remarkable stretchability (~622%), high electrical conductivity (5.13 S m−1), and good adhesion strength on varying substrates. We further demonstrate the capability of facilely printing such hydrogels into complex geometries like mesh and rhombus patterns with high resolution and robust integration. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD).Research Design and Methods: We followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD.Results: During a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of loge-transformed OC 0.51 [95% CI 0.35-0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44-0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of loge-transformed OC 0.49 [95% CI 0.33-0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38-0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed.Conclusions: Lower OC levels were associated with an increased risk of incident diabetes and DKD. [ABSTRACT FROM AUTHOR]

Background: Glucokinase (GCK) plays a central role in glucose regulation. The heterozygous mutations of GCK can cause a monogenic form of diabetes, maturity-onset diabetes of the young (MODY) directly. In our study, we aimed to explore the mechanism of the novel mutation GCK p.Ala259Thr leading to glucokinase deficiency and hyperglycemia. Methods: Thirty early-onset diabetes pedigrees were referred to whole exome sequencing for novel mutations identification. Purified wild-type and mutant GCK proteins were obtained from E.coli systems and then subjected to the kinetic and thermal stability analysis to test the effects on GCK activity. Results: One novel missense mutation GCK p.Ala259Thr was identified and co-segregated with diabetes in a Chinese MODY2 pedigree. The kinetic analysis showed that this mutation result in a decreased affinity and catalytic capability for glucose. The thermal stability analysis also indicated that the mutant protein presented dramatically decreased activity at the same temperature. Conclusion: Our study firstly identified a novel MODY2 mutation p.Ala259Thr in Chinese diabetes pedigrees. The kinetic and thermal stability analysis confirmed that this mutation caused hyperglycemia through severely damaging the enzyme activities and protein stability. [ABSTRACT FROM AUTHOR]

Objective: To explore the potential relevance of muscle mass as a variable contributor to BMI in limitations on BMI-based predictions of diabetes remission (DR) after Roux-en-Y gastric bypass (RYGB).Research Design and Methods: We evaluated the relationship between muscle mass and BMI in 501 patients with type 2 diabetes mellitus and overweight or obesity, of whom 186 patients who underwent RYGB were studied for determination of the role of baseline muscle mass and BMI in predicting DR. Muscle mass was assessed by estimated fat-free mass index (eFFMI) and psoas cross-sectional area (CSA).Results: A nonlinear relationship existed between psoas CSA and BMI, whereas psoas CSA showed a highly positive correlation with eFFMI. Baseline psoas CSA and eFFMI were better than BMI for predicting 1- and 5-year DR.Conclusions: The nonlinear relationship between muscle mass and BMI may partially contribute to BMI limitations in predicting DR after RYGB. [ABSTRACT FROM AUTHOR]

Background and Aims: Advanced glycation end products (AGEs) are reported to be correlated with diabetic vascular complications. This study aimed to investigate the association between AGEs and carotid atherosclerosis (CAS) as a surrogate marker of cardiovascular disease (CVD).Methods and Results: A total of 1006 patients with type 2 diabetes were included. CAS was defined as the presence of carotid arterial atherosclerotic plaque in any of bilateral carotid artery segments measured by ultrasonography. AGEs were measured by the noninvasive skin autofluorescence method. AGEage index was calculated as AGEs × age/100. Patients with CAS showed a significantly higher AGEage (P < 0.01), and the prevalence of CAS increased with ascending AGEage levels (P for trend < 0.001). Logistic regression analysis revealed that AGEage was significantly positively associated with odds of CAS, and the odds ratios of the presence of CAS across quartiles of AGEage were 1.00, 3.00 [95% confidence interval (CI) 1.90-4.74], 4.04 (95%CI 2.50-6.53) and 4.99 (95%CI 2.97-8.40) for the multivariable-adjusted model (P for trend <0.001), respectively. In the fully adjusted model, each 5.0 increase in AGEage was associated with a 0.019 mm increment in carotid intima-media thickness. Furthermore, AGEage presented an acceptable predictive value for CAS, with an optimal cutoff point of 43.2, and the sensitivity, specificity and area under the curve (AUC) were 74.5% (95%CI 70.7-78.1%), 61.9% (95%CI 57.2-66.4%) and 0.735 (0.706-0.762), respectively.Conclusion: AGEage, the noninvasive measurement of AGEs combined with age is a promising approach for triaging patients at high risk of CVDs. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to explore the immunological characteristics and cytokine profile of the initial stage of type 1 diabetes. Patients and Methods: In total, 123 age- and sex-matched subjects with newly diagnosed classic type 1 diabetes mellitus (T1ADM), fulminant type 1 diabetes mellitus (FT1DM), and normal glucose tolerance (NGT) were enrolled. Serum cytokine levels were measured using Milliplex MAP multifactor detection. Results: There was a significant increase in the levels of transforming growth factor β (TGFβ 1) and TGFβ 2 and decrease in programmed death-1 (PD-1), PD ligand 1 (PD-L1), pro-inflammatory cytokines, and anti-inflammatory cytokines in type 1 diabetes patients compared with the NGT subjects (all P < 0.05). There was no significant difference in C-reactive protein (CRP) and blood routine indicators between the two groups. Type 1 diabetes was further divided into T1ADM and FT1DM subgroups. FT1DM patients had much higher CRP levels than T1ADM patients (4.90 [0.95– 26.05] mg/L vs 0.39 [0.20– 0.74] mg/L, P < 0.01). Blood routine results showed that the number of leukocytes was significantly increased in FT1DM compared with that in T1ADM (9.2 [5.1– 18.8] × 109 cells/L vs 5.4 [4.5– 6.7] × 109 cells/L, P < 0.01). In FT1DM patients, neutrophil% was increased, and lymphocyte% was declined significantly, compared with that in T1ADM patients (neutrophil%: 80.2 [59.2– 85.2]% vs 59.5 [54.8– 64.0]%; lymphocyte%: 18.3 [10.1– 32.3]% vs 32.6 [26.8– 35.9]%; both P < 0.01). However, there was no difference between FT1DM and T1ADM in cytokine profile except for the decrease in CTLA-4 in T1ADM (P < 0.05). Conclusion: Compared with T1ADM, CRP and leukocytes' levels were increased significantly in FT1DM, with an increase in neutrophil% and decline in lymphocyte%, suggesting that FT1DM may have more abrupt onset and occur as a more serious subtype of type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Purpose: Although fibroblast growth factor-23 (FGF23) is involved in the development of metabolic diseases, its association with metabolic-associated fatty liver disease (MAFLD) remains unknown. We explored the relationship between serum fibroblast growth factor-23 level, metabolic associated fatty liver disease, and liver fat content. Patients and Methods: Participants were enrolled from communities in Shanghai. Serum fibroblast growth factor-23 level was determined using two-side sandwich enzyme-linked immunosorbent assays. MAFLD was diagnosed using the international expert consensus (2020) criteria. Liver fat content was assessed using ultrasound. Results: We enrolled 1827 individuals aged 30– 80 years (mean age, 59.4± 7.3 years). MAFLD was diagnosed in 445/1393 (31.9%) non-diabetic participants and 245/434 (56.5%) diabetic participants. After adjusting for confounders, one standard deviation increase in serum FGF23 was associated with MAFLD in diabetic (odds ratio, 1.27; 95% confidence interval, 1.15– 1.49; P< 0.001) and non-diabetic (odds ratio, 1.28; 95% confidence interval, 1.07– 1.74; P=0.030) groups. In a fully adjusted linear regression model, serum FGF23 emerged as a positive determinant of liver fat content in both diabetic and non-diabetic groups (P=0.039; P=0.034). Conclusion: Participants with MAFLD had higher serum fibroblast growth factor-23 level than those without MAFLD, regardless of diabetes status. Serum fibroblast growth factor-23 was independently related to MAFLD and liver fat content. [ABSTRACT FROM AUTHOR]

Although obesity occurs in most of the patients with type 2 diabetes (T2D), a fraction of patients with T2D are underweight or have normal weight. Several studies have linked the gut microbiome to obesity and T2D, but the role of gut microbiota in lean individuals with T2D having unique clinical characteristics remains unclear. A metagenomic and targeted metabolomic analysis is conducted in 182 lean and abdominally obese individuals with and without newly diagnosed T2D. The abundance of Akkermansia muciniphila (A. muciniphila) significantly decreases in lean individuals with T2D than without T2D, but not in the comparison of obese individuals with and without T2D. Its abundance correlates inversely with serum 3β‐chenodeoxycholic acid (βCDCA) levels and positively with insulin secretion and fibroblast growth factor 15/19 (FGF15/19) concentrations. The supplementation with A. muciniphila is sufficient to protect mice against high sucrose‐induced impairment of glucose intolerance by decreasing βCDCA and increasing insulin secretion and FGF15/19. Furthermore, βCDCA inhibits insulin secretion and FGF15/19 expression. These findings suggest that decreased abundance of A. muciniphila is linked to the impairment of insulin secretion and glucose homeostasis in lean T2D, paving the way for new therapeutic options for the prevention or treatment of diabetes. [ABSTRACT FROM AUTHOR]

Obesity and its related complications comprise a serious public health problem worldwide, and obesity is increasing in China. Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications. The pathogenesis of obesity is complex and not yet fully understood. Here, we review the current efficacy and safety of metabolic surgery, as well as recent progress in mechanistic studies and surgical procedures in China. The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety. [ABSTRACT FROM AUTHOR]

Abstract Background The contribution of glycemic variability to macrovascular complications remains unclear. We therefore investigated the association between glycemic variability and cervical and/or intracranial atherosclerosis in Chinese type 2 diabetic patients. Methods We conducted a cross-sectional study in 216 type 2 diabetic patients with a hemoglobin A1c of 8.3 ± 1.7% and a median diabetes duration of 9.0 years. The standard deviation of blood glucose values (SDBG) and the mean amplitude of glycemic excursion (MAGE) were calculated from continuous glucose monitoring system data for assessing glycemic variability while 24h mean blood glucose (MBG) was calculated for measuring overall blood glucose level. Magnetic resonance angiography (MRA) was used to detect cervical and/or intracranial plaque, and ultrasonography was used to quantify carotid intima-media thickness (IMT) as an index of subclinical atherosclerosis. Results One hundred and fifty-three patients (70.8%) presented with cervical and/or intracranial lesions on MRA among 216 patients in the study. Elder age, increased systolic blood pressure, increased MBG and elevated low density lipoprotein cholesterol were independent contributors to plaque formation. In patients without stenosis (n = 63), SDBG (r = 0.412, P = 0.001) and MAGE (r = 0.365, P = 0.005) were both correlated with carotid IMT and these relationships remained significant in multiple linear regression analysis (multiple R2 = 0.314 for the model including SDBG and multiple R2 = 0.268 for the model including MAGE). However, SDBG and MAGE were not significantly different among patients with different stenosis degrees. Conclusions Glycemic variability is associated with subclinical atherosclerosis in Chinese type 2 diabetic patients.

Aims: Recently, neck circumference (NC) has been proposed as a new anthropometric index for assessing upper body fat, which has a close relationship with cardiovascular diseases (CVDs) and their risk factors. The purpose of this study was to explore the role of NC in identifying subclinical atherosclerosis, an early stage of CVD, in a Shanghai community population. Materials and methods: We enrolled 1387 subjects (486 men and 901 women) from the Shanghai community. Anthropometric measurements, including NC and waist circumference (WC), were taken for all subjects. Carotid intima media thickness (C‐IMT) was determined by carotid ultrasonography. Elevated NC was defined as NC ≥ 38.5 cm in men and NC ≥ 34.5 cm in women. Results: There was a positive correlation between NC and C‐IMT, and this association remained significant even after adjustment for BMI (P =.015; P =.038). After adjusting for confounding factors, the additional risks of elevated C‐IMT were 58% and 33% for each SD increase in NC in men and women, respectively (P =.003; P =.009). The NC cutoffs could identify 53.38% of men and 43.07% of women with elevated C‐IMT, which was comparable to the identification of 56.08% of men and 42.57% of women with elevated C‐IMT using WC cutoffs (P =.218; P =.920). Conclusions: NC was significantly and positively correlated with C‐IMT. The cutoffs of NC could be helpful to identifying subclinical atherosclerosis in a community‐based population, and the identification showed no difference compared to that using WC cutoffs. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To define the target value for the percentage coefficient of variation for glucose (%CV) as a measure of glycemic variability (GV) in Chinese diabetes patients. Materials and Methods: This retrospective study included 3,007 diabetes patients who underwent continuous glucose monitoring for 3 days. Type 2 diabetes was divided into groups according to the received treatment: group 1, non‐insulinotropic agent (n = 138); group 2, insulinotropic agent (n = 761); group 3, basal insulin therapy (n = 100); group 4, premixed insulin (n = 784); and group 5, intensive insulin therapy (n = 612). Type 1 diabetes patients were included as group 6 (n = 612). %CV and percentage of time per day within, below (3.9mmol/L; TBR3.9) and above (10.0 mmol/L) the target glucose range (3.9–10.0 mmol/L) were computed. TBR3.9 ≥4% was defined as excessive hypoglycemia. Results: Type 2 diabetes with a premixed or intensive insulin regimen had an increased %CV compared with those receiving oral therapy or basal insulin. The upper limit of %CV in group 1 was 33%, which was adopted as the threshold to define excessive GV. For each treatment group, the percentage of people with TBR3.9 ≥4% was significantly greater in the subgroup with %CV >33% than ≤33% (P < 0.001). In participants who achieved TBR3.9 <4%, the time per day spent within the target glucose range of 3.9–10.0 mmol/L > 70% and time per day above 10.0 mmol/L <25%, the 95th percentile of %CV was 32.70%. Further receiver operating characteristic curve analysis showed that the cut‐off values of %CV for predicting TBR3.9 ≥4% varied by the type of diabetes and glycated hemoglobin categories. Conclusions: A %CV of 33% was set as the threshold for excess glucose variability in Chinese diabetes patients. Meanwhile, glycated hemoglobin and the type of diabetes should be considered for the goal‐setting of %CV. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first‐line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF) or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon‐like peptide 1 receptor agonist (GLP‐1RA) or sodium–glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA1C) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA1C levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA1C targets, and GLP‐1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid‐lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD. [ABSTRACT FROM AUTHOR]

aim of this study was to elucidate the association of NC with urine albumin-to-creatinine ratio (UACR) and MAU. Methods: A total of 1882 Shanghai community residents were enrolled (816 men and 1066 women), with age ranging from 40 to 80 years. Anthropometric parameters, including NC, and biochemical indices were measured. MAU was determined if 30 mg/g ≤ UACR < 300 mg/g. An elevated NC was defined as NC ≥ 38.5 cm for men and NC ≥ 34.5 cm for women. Results: Individuals with an elevated NC had significantly higher prevalence of MAU and UACR values than those with normal NC in both men and women (all P < 0.05). The logistic regression analysis showed that there were significant and positive associations between elevated NC and the increasing risk of MAU after adjusting for lipid profile and glycemic indices (P = 0.007 for men and P = 0.009 for women). After further adjusting for blood pressure, elevated NC caused an 69.3% additional risk of MAU in men (P = 0.037) and the positive correlation in women disappeared (P = 0.131). Conclusion: There was an independent and positive association between elevated NC and the risk of MAU in men in the Chinese community population. Chinese Clinical Trial Registry (Www.chictr.org.cn) Registration Number: ChiCTR1900024011. [ABSTRACT FROM AUTHOR]

Objective. Neck circumference (NC) is a simple anthropometric index for the assessment of upper body obesity. Thyroid hormones are closely related to obesity, body fat distribution indicators, and metabolic parameters. However, there are currently no reports on the association between NC and thyroid hormones in the Chinese population. This study aimed to explore the relationship between NC and thyroid hormones in men with normal thyroid function. Methods. A total of 737 euthyroid men from Shanghai communities were enrolled. Anthropometric parameters, including NC and waist circumference (WC), were measured. Serum thyroid hormones were measured by electrochemical luminescence immunoassay. Results. NC, WC, and body mass index (BMI) were significantly positively correlated with serum free triiodothyronine (FT3) (all P < 0.05). FT3 levels all presented significant upward trends with the increase in NC, WC, or BMI quartiles (all P for trend < 0.05), whereas there were no significant correlations between the three obesity indices and free thyroxine or thyroid-stimulating hormone (both P > 0.05). After adjustment for metabolic confounding factors such as age, blood pressure, blood glucose, lipid profiles, and CRP in multiple linear regression analysis, the correlation between FT3 and NC disappeared (standardized β = −0.015, P = 0.705), and FT3 remained significantly associated with WC (standardized β = 0.103, P = 0.012) and BMI (standardized β = 0.082, P = 0.047). Conclusions. In euthyroid men from Shanghai communities, there was no independent correlation between serum FT3 levels and NC. The trial was registered with ChiCTR1900024011. [ABSTRACT FROM AUTHOR]

Background: The simultaneous assessment of visceral adiposity and muscle mass might be useful to monitor the risk of non-alcoholic fatty liver disease (NAFLD) progression in large population. We aimed to investigate the value of serum creatinine-to-cystatin C ratio (CCR) in evaluating these two parameters and predicting liver steatosis and fibrosis. Methods: 154 overweight/obese inpatients (49 males, 105 females) scheduled for bariatric surgery and 49 non-overweight/obese volunteers (18 males, 31 females) responded to the hospital advertisement were involved in the cross-sectional study. Liver steatosis and fibrosis were diagnosed with transient elastography (TE). The psoas muscle area (PMA) and visceral fat area (VFA) were measured using magnetic resonance imaging. Results: The body mass index, insulin resistance, and lipid profiles showed significant differences between the CCR tertiles. Multiple regression analyses revealed that the CCR was significantly associated with the controlled attenuation parameter (β = −0.30, P = 0.006 in males; β = −0.19, P = 0.017 in females) and liver stiffness measurements in males (β = −0.246, P = 0.044). A low CCR was associated with moderate-to-severe steatosis (P < 0.001), significant liver fibrosis (P < 0.01), and excellent predictive power for these two conditions (P < 0.01). The CCR had a negative correlation with the VFA/PMA ratio (r = −0.584, P < 0.001 in males; r = −0.569, P < 0.001 in females). Conclusions: The CCR is a serum marker for muscle-adjusted visceral fat mass, and a low CCR is associated with an increased risk of progressive NAFLD. [ABSTRACT FROM AUTHOR]

Middle‐aged and elderly women are at a higher risk of subclinical hypothyroidism (SHypo). Menopause is an important period of metabolic change in women and thyroid hormones are closely related to metabolic status. Neck circumference (NC) is a simple anthropometric index that reflects upper body fat accumulation. Therefore, this study aimed to explore the relationship between NC and thyroid hormones in postmenopausal women. A total of 1050 postmenopausal women were enrolled from Shanghai Zhabei communities (888 euthyroid subjects and 162 SHypo patients). Anthropometric parameters, including NC, were measured. The measurements of serum thyroid hormones were performed by electrochemical luminescence immunoassay. The results showed NC was positively correlated with thyroid‐stimulating hormone (TSH) (r =.064, P =.039). TSH and the proportion of SHypo patients increased significantly in those with elevated NC (both P <.05). In logistic regression analysis, the risk of SHypo increased by 46.4% in those with elevated NC (OR = 1.464 [1.035–2.071], P =.031). After adjusting for metabolic confounding factors, the positive association disappeared (P =.112). Multiple linear regression analysis showed there were no significant correlations between NC and TSH in either univariate or multivariate model in the total population (both P >.05). And in the subgroup analysis of euthyroid and SHypo individuals, NC was also not related to TSH (all P >.05). In conclusion, there was no independent association between NC, a simple anthropometric index for upper body fat accumulation, and serum TSH levels in Chinese euthyroid and SHypo postmenopausal women. [ABSTRACT FROM AUTHOR]

Previous studies found that thyroid hormones stimulate osteoblast-like cells to secrete osteocalcin. We aimed to investigate the association between serum thyroid hormone and serum osteocalcin in euthyroid population. The study recruited 1152 community-based euthyroid subjects (average age 59 ± 8 years), among whom 677 were women. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and osteocalcin were measured by electrochemiluminescence immunoassays. After adjusting for age and gender, partial correlation analysis showed that FT3 and FT3/FT4 were both positively correlated with body mass index (BMI) and serum osteocalcin levels (all P < 0.05) and BMI was negatively correlated with serum osteocalcin levels P < 0.01 , while FT4 and TSH were not correlated with serum osteocalcin levels (all P > 0.05). Age, gender, blood pressure, thyroid hormones, and multiple metabolic risk factors were included in the ridge regression model. FT3 and FT3/FT4 were independently and positively associated with serum osteocalcin levels (all P < 0.05), while BMI was independently and negatively associated with serum osteocalcin levels P < 0.01 . The mediating effect model showed that FT3 and FT3/FT4 suppressed the negative association between BMI and serum osteocalcin levels, with suppressing effects of 6.41% and 10.39%, respectively. In euthyroid subjects, both FT3 and FT3/FT4 were positively associated with serum osteocalcin levels, and they further suppressed the negative association between BMI and serum osteocalcin levels. [ABSTRACT FROM AUTHOR]

Aim. To investigate the effects of alcohol on serum glycated albumin (GA) levels in Chinese men. Methods. A total of 2314 male subjects from the Jinuo ethnic group in China were enrolled. Of these, 986 subjects drank alcohol frequently and 404 subjects did not. Lifestyle information was gathered by using a questionnaire, and measurements of blood pressure, body mass index, blood glucose level, liver function, and kidney function were collected. GA was measured by using an enzymatic method. Frequent drinking was defined as a history of drinking ethanol > 80 g/d within the past two weeks. Nondrinking was defined as no alcohol consumption in the past three months. Subjects with an alcohol intake between 0 and 80 g/d in the past two weeks were included in the drinking-occasionally group. Analysis of variance (ANOVA), correlation analysis, and linear regression were used to evaluate the effects of drinking on serum GA levels. Decision tree regression (DTR) algorithm was used to evaluate the effect of features (variables) on GA levels. Results. We found that male subjects who drank frequently had significantly lower serum GA levels than subjects who did not drink (13.0 ± 1.7 vs. 14.1 ± 3.7, p < 0.05). Spearman's correlation analysis calculated a coefficient of −0.152 between drinking and GA (p < 0.005). Linear regression established that drinking was an independent predictor for GA levels with a standardized regression coefficient of −0.144 (p < 0.05). Decision tree regression showed that the effect of drinking on GA levels (0.0283) is five times higher than that of smoking (0.0057). Conclusions. Frequent alcohol consumption could result in decreased GA levels in men of the Jinuo ethnic group in China. [ABSTRACT FROM AUTHOR]

Abstract Background Over the past two decades, the prevalence of overweight or obesity has increased in China. The aims of this study were to firstly assess the baseline prevelences and the risk factors for overweight and obesity, and secondly to detect the changes of body mass index (BMI) over a follow-up period in Chinese adults in Shanghai. Methods The data set of a population-based longitudinal study was analyzed. Anthropometric and biochemical data were collected for 5364 subjects (aged 25–95 years) during a period of 1998–2001. Among those individuals, 3032 subjects were interviewed and reexamined at the second survey from 2003 to 2004. Then the standardized prevalences for overweight and obesity were calculated using baseline data; the possible contributing factors of overweight and obesity were detected using binary logistic regression analysis; and the changes of BMI were evaluated after an average of 3.6-year follow-up period. Results (1) According to the WHO standard and the Chinese standard, the sex- and age-standardized prevalences were 27.5% and 32.4% for overweight, and 3.7% and 9.1% for obesity, respectively. (2) The risks of overweight and obesity differed among different age groups. Family history of obesity increased the risk of overweight and obesity by about 1.2-fold for both genders. Current male smokers had a lower risk of overweight and obesity (OR = 0.76, p < 0.05) than nonsmokers. In contrast, current male drinkers had a higher risk of overweight and obesity (OR = 1.42, p < 0.05) than nondrinkers. Compared with low-educated women, medium- and high- educated women were at lower risk of overweight and obesity, and the corresponding ORs (95% CIs) were 0.64 (0.52–0.79) and 0.50(0.36–0.68), respectively. (3) The annual changes of BMI means ranged from an increase of 0.1 kg/m2 to a decrease of 0.2 kg/m2 (by genders and age groups). Meanwhile, the BMI increase was statistically significant in the 35–44 years age group, and the BMI decrease was significant above 65 years for both genders. Conclusion This study showed high prevalence of overweight and obesity in Shanghai metropolis populations. The risk factors of overweight and obesity were multifactorial and gender specific. After 3.6 years, BMI means changed slightly, BMI increased mainly in middle-aged individuals and decreased in old individuals.

Osteocalcin is a bone-derived hormone that plays an important role in the crosstalk between bone and energy metabolism. Previous studies have found that treatment with uncarboxylated osteocalcin can protect mice from high-fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the potential mechanisms remain unclear. Although the G protein-coupled receptor family C group 6 subtype A (GPRC6A) is the putative receptor of osteocalcin, there is no direct evidence showing that GPRC6A mediates the effects of uncarboxylated osteocalcin in alleviating NAFLD in mice. We aimed to figure out this using liver-specific GPRC6A knockout (GPRC6ALKO) mice. Consistent with previous studies, uncarboxylated osteocalcin significantly protected high-fat diet-fed wild-type mice from obesity and NAFLD, while it did not protect high-fat diet-fed GPRC6ALKO mice from NAFLD. Differential mRNA expression of lipogenesis and lipolysis between GPRC6ALKO mice and control mice revealed that GPRC6A mediated the effects of osteocalcin in alleviating NAFLD through inhibiting lipid synthesis and promoting lipolysis. In conclusion, this study found that uncarboxylated osteocalcin alleviates NAFLD in mice through the GPRC6A signaling pathway. Our study suggests that liver GPRC6A may be a potential target for treating NAFLD. [ABSTRACT FROM AUTHOR]

Mitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of 17 mitochondrial Fe-S cluster assembly genes, was the most significant induced gene in the browning program of white adipose tissue. Using lentiviral-delivered shRNA in vitro , we determined that Bola3 deficiency inhibited thermogenesis activity without affecting lipogenesis in differentiated beige adipocytes. The inhibition effect of Bola3 knockdown might be through impairing mitochondrial homeostasis and lipolysis. This was evidenced by the decreased expression of mitochondria related genes and respiratory chain complexes, attenuated mitochondrial formation, reduced mitochondrial maximal respiration and inhibited isoproterenol-stimulated lipolysis. Furthermore, BOLA3 mRNA levels were higher in human deep neck brown fat than in the paired subcutaneous white fat, and were positively correlated with thermogenesis related genes (UCP1, CIDEA, PRDM16, PPARG, COX7A1, and LIPE) expression in human omental adipose depots. This study demonstrates that Bola3 is associated with adipose tissue oxidative capacity both in mice and human, and it plays an indispensable role in beige adipocyte thermogenesis via maintaining mitochondrial homeostasis and adrenergic signaling-induced lipolysis. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon‐like peptide‐1 receptor agonist, as an add‐on to metformin therapy in Chinese patients with type 2 diabetes (T2D). Materials and methods: This was a multicentre, randomized, double‐blind, placebo‐controlled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%‐10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28‐week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. Results: The least‐square mean (standard error) change in HbA1c levels was significantly greater (P <.001 for superiority) in the PEX168 groups (−1.16% [0.08%] and −1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P <.001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti‐PEX168 antibodies were noted in less than 2% of patients. No treatment‐emergent serious adverse events occurred. Conclusion: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin. [ABSTRACT FROM AUTHOR]

Background: Serum adipocyte fatty acid-binding protein (A-FABP) and thyroid hormones are closely associated with metabolic disorders; however, their relationship remains unknown. We aimed at investigating the associations of serum A-FABP levels with single and composite indices of the thyroid system. Methods: The study included 1057 community-based euthyroid participants (age range: 27–81 years) in Shanghai, among whom 601 were women. Serum free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) were measured by electrochemical luminescence immunoassay. The thyroid feedback quantile-based index (TFQI), thyrotropin index (TSHI), and thyrotroph thyroxine resistance index (TT4RI) were calculated to evaluate central sensitivity to thyroid hormones. Peripheral sensitivity to thyroid hormones was evaluated by the fT3 to fT4 ratio (fT3/fT4). Enzyme-linked immunosorbent assay was used to measure serum A-FABP levels. Results: Serum A-FABP levels were 6.41 [95% confidence interval: 6.10–6.74] ng/mL among all subjects. Multiple cardiovascular metabolic risk factors were adjusted in the multivariate linear regression analysis and the multinomial logistic regression analysis (nonordinal). In both sexes, serum A-FABP levels were positively associated with fT4 (men: standardized β = 0.150, p = 0.001; women: standardized β = 0.218, p < 0.001), TFQI (men: standardized β = 0.119, p = 0.009; women: standardized β = 0.165, p < 0.001), and TSHI (men: standardized β = 0.108, p = 0.017; women: standardized β = 0.114, p = 0.005); while they were negatively associated with fT3/fT4 (men: standardized β = −0.122, p = 0.008; women: standardized β = −0.129, p = 0.001). Serum A-FABP levels were not associated with fT3, TSH, or TT4RI. Compared with the first quartile group of TFQI, for every 10 ng/mL increase in A-FABP, the odds ratio (OR) for the third quartile group of TFQI was 2.213 in women (p = 0.035); the ORs for the fourth quartile group of TFQI were 2.614 in men (p = 0.022) and 3.425 in women (p = 0.002). Conclusions: In a euthyroid population, increased serum A-FABP levels were associated with decreased sensitivity to thyroid hormones, suggesting that A-FABP may mediate the "cross-talk" between adipose tissue and the thyroid system. [ABSTRACT FROM AUTHOR]

Nocturnal hypoglycemia is a serious complication of insulin-treated diabetes, and it is often asymptomatic. A novel CGM metric-gradient was proposed in this paper, and a method of combining mean sensor glucose (MSG) and gradient was presented for the prediction of nocturnal hypoglycemia. For this purpose, the data from continuous glucose monitoring (CGM) encompassing 1,921 patients with diabetes were analyzed, and a total of 302 nocturnal hypoglycemic events were recorded. The MSG and gradient values were calculated, respectively, and then combined as a new metric (i.e., MSG+gradient). In addition, the prediction was conducted by four algorithms, namely, logistic regression, support vector machine, random forest, and long short-term memory. The results revealed that the gradient of CGM showed a downward trend before hypoglycemic events happened. Additionally, the results indicated that the specificity and sensitivity based on the proposed method were better than the conventional metrics of low blood glucose index (LBGI), coefficient of variation (CV), mean absolute glucose (MAG), lability index (LI), etc., and the complex metrics of MSG+LBGI, MSG+CV, MSG+MAG, and MSG+LI, etc. Specifically, the specificity and sensitivity were greater than 96.07% and 96.03% at the prediction horizon of 15 minutes and greater than 87.79% and 90.07% at the prediction horizon of 30 minutes when the proposed method was adopted to predict nocturnal hypoglycemic events in the aforementioned four algorithms. Therefore, the proposed method of combining MSG and gradient may enable to improve the prediction of nocturnal hypoglycemic events. Future studies are warranted to confirm the validity of this metric. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to explore the association of 1,5-anhydroglucitol with acute C peptide response (ACPR) to arginine among patients with type 2 diabetes. Methods. Patients with type 2 diabetes were enrolled from the Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital. ACPR was assessed using arginine stimulation test. Decreased β-cell function was defined as ACPR < 2.1. Multivariable logistic regression models were used to demonstrate the association between 1,5-anhydroglucitol and decreased β-cell function. Results. Finally, 623 patients with type 2 diabetes were enrolled into the analysis. Multivariable-adjusted odds ratios for decreased β-cell function across quartiles of 1,5-anhydroglucitol were 1.00, 0.47 (95% confidence interval (CI) 0.23-0.99), 0.41 (95% CI 0.20-0.84), and 0.27 (95% CI 0.13-0.57) ( P trend = 0.042), respectively. When 1,5-anhydroglucitol was considered as a continuous variable after logarithm, the corresponding odds ratio was 0.40 (95% CI 0.23-0.71). Conclusions. We demonstrated a dose-response linear association between 1,5-anhydroglucitol and ACPR. 1,5-Anhydroglucitol was likely to be associated with β-cell function. Further analysis with large sample size and prospective study design is warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Background. Accumulating evidence has shown that neck circumference (NC) is associated with obesity-related metabolic abnormalities. Nonalcoholic fatty liver disease (NAFLD) is regarded as a liver manifestation of metabolic syndrome. This study aimed to investigate the relationship between NC and liver fat content (LFC) and NAFLD. Methods. A total of 1698 subjects (577 men and 1121 women) from the Shanghai community were enrolled. All the subjects underwent NC measurement and biochemical measurements. LFC was calculated using the parameters from abdominal ultrasound images. Elevated NC was defined as NC ≥38.5 cm in men and NC ≥34.5 cm in women. Results. Subjects with NAFLD based on the LFC measurement had higher values of NC, liver enzyme profiles, homoeostasis model assessment-insulin resistance index, and LFC than those without NAFLD (all P < 0.05), irrespective of sex. NC showed an upward trend with the increase of LFC in both men and women (both P < 0.05). An elevated NC could identify 55.22% of men and 50.29% of women with NAFLD based on quantitative ultrasonography. The positive correlation between NC and LFC remained significant even after adjustment for central obesity (both P < 0.05). After adjusting for confounding factors, the risk of NAFLD in subjects with an elevated NC was 1.52-fold higher in men (P = 0.036) and 2.31-fold higher in women (P < 0.001). Conclusions. There was a significant and positive correlation between NC and LFC. The risk of NAFLD increased significantly in subjects with an elevated NC. [ABSTRACT FROM AUTHOR]

Background: Obesity is closely related to thyroid hormones; however, the relationship between abdominal fat distribution and thyroid hormones has rarely been explored. Objectives: This study aimed to explore the relationship between abdominal fat distribution and free triiodothyronine (FT3) and FT3 to free thyroxine (FT4) ratio (FT3/FT4) in a euthyroid population. Methods: The present study enrolled 1,036 participants (age range 27–81 years; 445 men and 591 women). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were determined by magnetic resonance imaging. FT3, FT4, and thyroid-stimulating hormone were measured by an electrochemical luminescence immunoassay. Results: In both men and women, SFA increased according to the increase of FT3 and FT3/FT4 tertiles (p for trend <0.05), while VFA did not significantly change. In the multivariate stepwise regression analysis, SFA was independently and positively related to FT3 in both men and women, the standardized β (95% CI) were 0.183 (0.094, 0.272) (p < 0.001) and 0.089 (0.007, 0.171) (p = 0.033), respectively. Moreover, SFA was independently and positively related to FT3/FT4 in men, the standardized β (95% CI) was 0.196 (0.101, 0.290) (p < 0.001). However, VFA was not related to either FT3 or FT3/FT4 in both genders. Conclusions: Abdominal subcutaneous fat was independently related to increased FT3 in a euthyroid population. [ABSTRACT FROM AUTHOR]