Low-dose metformin targets the lysosomal AMPK pathway through PEN2.

Metformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects1-4. For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6. We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects.

Insight to the association among fibroblast growth factor 21, non-alcoholic fatty liver disease and cardiovascular outcomes: A population-based study.

OBJECTIVE: We aimed to investigate whether there was a joint effect of fibroblast growth factor 21 (FGF21) and non-alcoholic fatty liver disease (NAFLD) or interaction on the incidence of cardiovascular diseases based on a community-dwelling population. METHODS: Serum FGF21 levels were determined using an enzyme-linked immunosorbent method. NAFLD was diagnosed via ultrasonography. Multivariable-adjusted cox proportional hazards models were used to assess the joint effects of FGF21 and NAFLD on the major adverse cardiovascular events (MACE). RESULTS: A total of 1194 participants were enrolled in the final analysis. The multivariable-adjusted hazard ratio (HR) of MACE was 1.84 (95% confidence interval (CI) 1.18-2.86) in participants with diagnosed NAFLD at baseline, compared with those without NAFLD at baseline. The multivariable-adjusted HRs of MACE across quintiles of serum FGF21 levels at baseline were 1.00, 1.48 (95%CI 0.68-3.21), 2.01 (95%CI 0.98-4.13), 1.94 (95%CI 0.94-4.02) and 2.14 (95%CI 1.03-4.44) respectively. Participants with high FGF21 levels and NAFLD at baseline showed the highest risk of MACE with a significant interaction between the presence of NAFLD and serum FGF21 levels. CONCLUSIONS: Both FGF21 and NAFLD were associated with MACE, while the association between FGF21 and MACE may be interacted by the presence of NAFLD at baseline.

Clusterin is closely associated with adipose tissue insulin resistance.

AIMS: Clusterin (encoded by CLU) is a novel adipokine. Serum clusterin levels were elevated in populations with obesity and diabetes. Adipose tissue insulin resistance (Adipo-IR) is proposed as an early metabolic defect that precedes systemic insulin resistance. Herein, we aimed to investigate the relationship between serum clusterin levels and Adipo-IR. CLU expression in human abdominal adipose tissues and clusterin secretion in human adipocytes was also explored. MATERIALS AND METHODS: A total of 201 participants (aged 18-62 years, 139 of whom were obese) were recruited. Enzyme-linked immunosorbent assay was used to measure serum clusterin levels. Adipo-IR was calculated from the product of fasting free fatty acids and fasting insulin levels. Transcriptome sequencing of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was performed. Human adipocytes were used to detect the secretion of clusterin. RESULTS: Serum clusterin levels were independently associated with Adipo-IR after adjusting for several confounding factors (standardised ß = 0.165, p = 0.021). CLU expression in VAT and SAT was associated with obesity-related metabolic risk factors. Higher CLU expression in VAT was accompanied by an increase in collagen accumulation. Clusterin secretion in differentiated human adipocytes was stimulated by insulin and inhibited by rosiglitazone. CONCLUSIONS: Clusterin is strongly associated with Adipo-IR. Serum clusterin may function as an effective indicator of adipose tissue insulin resistance.

Association of thyroid stimulating hormone and time in range with risk of diabetic retinopathy in euthyroid type 2 diabetes.

AIMS: Diabetic retinopathy (DR) can occur even in well-controlled type 2 diabetes, suggesting residual risks of DR in this population. In particular, we investigated the combined effect of thyroid function and glycaemic control assessed by an emerging metric, time in range (TIR) with DR. MATERIALS AND METHODS: In this cross-sectional study, a total of 2740 euthyroid patients with type 2 diabetes were included. Thyroid indicators, including thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, thyroid peroxidase antibody and thyroglobulin antibody, were measured. TIR was measured using continuous glucose monitoring data. RESULTS: Overall, the multivariable-adjusted odds ratios (ORs) for DR across ascending tertiles of TSH were 1.00 (reference), 1.06 (95% confidence interval [CI] 0.85-1.32), and 1.48 (95% CI 1.19-1.85). Even in well-controlled participants who achieved a TIR target of >70% (n = 1449), the prevalence of DR was 23.8%, which was significantly related to TSH (OR = 1.54, 95% CI 1.12-2.12, highest vs. lowest TSH tertile). Participants were then classified into 6 groups by the joint categories of TIR (>70%, ≤70%) and TSH (tertiles), and the multivariable-adjusted ORs for DR were highest in TIR ≤70% and the highest TSH tertile group (OR = 1.96, 95% CI 1.41-2.71) when compared with the TIR >70% and the lowest TSH tertile group. CONCLUSIONS: In type 2 diabetic patients with well-controlled glycaemic status, higher TSH within the normal range was associated with an increased risk of DR. The combination of suboptimal TSH and TIR further increased the risk of DR.

Association between glycaemia risk index (GRI) and diabetic retinopathy in type 2 diabetes: A cohort study.

AIM: To investigate the association between a new composite metric, glycaemia risk index (GRI), and incident diabetic retinopathy (DR). METHODS: A total of 1204 adults with type 2 diabetes without DR at baseline were included between 2005 and 2019 from a single centre in Shanghai, China. GRI was obtained from continuous glucose monitoring data at baseline. Cox proportion hazard regression analysis was used to assess the association between GRI and the risk of incident DR. RESULTS: During a median follow-up of 8.4 years, 301 patients developed DR. The multivariable-adjusted hazard ratios (HRs) for incident DR across ascending GRI quartiles (≤14 [reference], 15 ~ 28, 29 ~ 47 and > 47) were 1.00, 1.05 (95% CI 0.74-1.48), 1.33 (95% confidence interval [CI] 0.96-1.84) and 1.53 (95% CI 1.11-2.11), respectively. For each 1-SD increase in GRI, the risk of DR was increased by 20% (HR 1.20, 95% CI 1.07-1.33) after adjustment for confounders. CONCLUSIONS: In patients with type 2 diabetes, higher GRI is associated with an increased risk of incident DR. GRI has the potential to be a valuable clinical measure, which needs to be further explored in future studies.

Change of neck circumference in relation to visceral fat area: a Chinese community-based longitudinal cohort study.

BACKGROUND/OBJECTIVES: Neck circumference (NC) has been positively associated with visceral fat area (VFA) in cross-sectional studies. This study aimed to evaluate the effects of NC changes on VFA in a Chinese community-based longitudinal cohort. SUBJECTS/METHODS: Subjects recruited from Shanghai communities were followed up for 1.1-2.9 years. A total of 1421 subjects (men 578, women 843) were included, aged 24-80 years, with an average age of 57.8 ± 7.1 years. INTERVENTIONS/METHODS: Biochemical and anthropometric measurements, including NC, were obtained from all subjects. VFA was assessed by magnetic resonance imaging. Abdominal obesity was defined as a VFA ≥ 80 cm2. RESULTS: After a mean follow-up of 2.1 years, the NCs for men and women were 38.1 ± 2.3 cm and 33.8 ± 2.0 cm, respectively, and the average value of VFA was 84.55 (59.83-113.50) cm2. After adjusting for age, sex, body mass index, smoking, history of drinking, glycated hemoglobin, blood pressure and blood lipids, individuals who had gained a NC of more than 5% had 1.26 (95% CI: 1.05-1.49) times more visceral adipose tissue at follow-up than NC maintainers (NC change between -2.5% and 2.5%). In the non-abdominal obesity group at baseline (n = 683), after adjusting for confounding factors, changes in NC were associated with abdominal obesity (odd ratio 1.23, 95% CI: 1.09-1.39). CONCLUSIONS: Changes in NC were positively associated with VFA in a Chinese community-based cohort, suggesting that NC measurement is practical for assessing abdominal obesity.

Low total osteocalcin levels are associated with all-cause and cardiovascular mortality among patients with type 2 diabetes: a real-world study.

BACKGROUND: The association between osteocalcin and mortality has been scantly studied. We aimed to investigate the association between osteocalcin along with its trajectories and mortality based on long-term longitudinal data. METHODS: We performed a retrospective cohort study of 9413 type 2 diabetic patients with at least three measurements of total serum osteocalcin within 3 years since their first inpatient diagnosis of type 2 diabetes. Baseline, mean values of osteocalcin levels and their trajectories were used as exposures. A multivariable-adjusted Cox proportional hazards model was used to estimate the association of osteocalcin levels and their trajectories with mortality. RESULTS: During a mean follow-up of 5.37 years, 1638 patients died, of whom 588 were due to cardiovascular events. Multivariable-adjusted hazard ratios (HRs) across quintiles of baseline osteocalcin levels were 2.88 (95% confidence interval (CI) 2.42-3.42), 1.65 (95% CI 1.37-1.99), 1.17 (95% CI 0.96-1.42), 1.00, and 1.92 (95% CI 1.60-2.30) for all-cause mortality, and 3.52 (95% CI 2.63-4.71), 2.00 (95% CI 1.46-2.73), 1.03 (95% CI 0.72-1.47), 1.00, 1.67 (95% CI 1.21-2.31) for CVD mortality, respectively. When we used the mean values of osteocalcin as the exposure, U-shaped associations were also found. These U-shaped associations were consistent among patients of different baseline characteristics. Patients with a stable or even increasing trajectory of osteocalcin may have a lower risk of both all-cause and CVD mortality. CONCLUSIONS: A U-shape association between baseline osteocalcin and mortality was observed among patients with type 2 diabetes. Patients with lower levels of serum osteocalcin during follow-ups had higher risks for all-cause and cardiovascular mortality.

Clinical application guidelines for blood glucose monitoring in China (2022 edition).

Glucose monitoring is an important component of diabetes management. The Chinese Diabetes Society (CDS) has been producing evidence-based guidelines on the optimal use of glucose monitoring since 2011. In recent years, new technologies in glucose monitoring and more clinical evidence, especially those derived from Chinese populations, have emerged. In this context, the CDS organised experts to revise the Clinical application guidelines for blood glucose monitoring in China in 2021. In this guideline, we focus on four methods of glucose monitoring that are commonly used in clinical practice, including capillary glucose monitoring, glycated haemoglobin A1c, glycated albumin, and continuous glucose monitoring. We describe the definitions and technical characteristics of these methods, the factor that may interfere with the measurement, the advantages and caveats in clinical practice, the interpretation of glucose metrics, and the relevant supporting evidence. The recommendations for the use of these methods are also provided. The various methods of glucose monitoring have their strengths and limitations and cannot be replaced by one another. We hope that these guidelines could aid in the optimal application of common methods of glucose monitoring in clinical practice for better diabetes care.

The relationship between sex hormones and glycated hemoglobin in a non-diabetic middle-aged and elderly population.

BACKGROUND: Sex hormones are strongly linked to the occurrence and development of diabetes, and influence glycated hemoglobin (HbA1c) levels in diabetic population; but, the relationship between sex hormones and HbA1c in non-diabetic population remains unknown. This study aimed to explore the extent of influence of sex hormones on HbA1c levels in non-diabetic population. METHODS: A total of 1409 non-diabetic subjects, including 601 men and 808 postmenopausal women were recruited from Shanghai community. HbA1c was detected using high performance liquid chromatography, and hemoglobin level was determined by sodium lauryl sulfate colorimetry. Serum estradiol (E2), total testosterone (TT), and sex hormone binding globulin (SHBG) were measured by chemiluminescent microparticle immunoassays. RESULTS: The level of HbA1c was 5.6 (5.4-5.9) % in all subjects, with 5.6 (5.4-5.8) % in men and 5.7 (5.5-5.9) % in postmenopausal women. After adjusting for age, body mass index (BMI), and hemoglobin, E2 was positively correlated with HbA1c in men (r = 0.122, P = .003), and SHBG was inversely correlated with HbA1c (r = - 0.125, P < .001) in women. Other hormones were not correlated with HbA1c (all P > .05). Multivariate linear regression analysis showed that, except for traditional factors, such as age, hemoglobin, and BMI, E2 was another determinant of HbA1c (standardized ß = 0.137, P = .003) in men; besides, in women, SHBG was another determinant of HbA1c (standardized ß = - 0.178, P < .001), except for age and systolic blood pressure. CONCLUSION: After controlling for confounding factors, two sex hormones, as E2 and SHBG could influence HbA1c levels in non-diabetic population.

Neck circumference predicts development of carotid intima-media thickness and carotid plaque: A community-based longitudinal study.

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.

Neck circumference for predicting the occurrence of future cardiovascular events: A 7.6-year longitudinal study.

BACKGROUND & AIMS: This study aimed to investigate whether neck circumference (NC) could be used to predict future cardiovascular (CV) events in a community-based Chinese cohort. METHODS AND RESULTS: We enrolled 1435 participants aged 50-80 years (men, 43.62%) from communities in Shanghai. High NC was defined as NC ≥ 38.5 cm in men and NC ≥ 34.5 cm in women. Kaplan-Meier analysis and Cox proportional hazards regression were performed to explore the association between NC and CV events. During a mean follow-up period of 7.6 years, 148 CV events (10.31%) occurred. The incidence of CV events was higher in men than in women (83 (13.26%) vs. 65 (8.03%), P = 0.002). Multivariable-adjusted Cox regression analysis showed that for every 1-SD increase in NC in the whole population, the hazard ratio (HR) of CV events was 1.45 (95% confidence interval [CI], 1.15-1.83). The dose-response association between NC and CV events was significant in men (HR, 1.37, 95% CI, 1.10-1.71) but not in women (HR, 1.19, 95% CI, 0.94-1.52). In comparison with participants showing low baseline NC, those with high baseline NC showed a significantly higher risk of CV events (HR, 1.59, 95% CI, 1.14-2.22). Further stratified by sex, the positive association remained significant in men (HR, 1.90, 95% CI, 1.21-2.98) but not in women (HR, 1.25, 95% CI, 0.75-2.07). CONCLUSION: NC was significantly associated with the risk of future CV events in middle-aged and elderly populations in the community and was a better predictor in men.

Associations between sex hormones and metabolic-associated fatty liver disease in a middle-aged and elderly community.

Metabolic-associated fatty liver disease (MAFLD) was proposed by an international expert consensus to replace non-alcoholic fatty liver disease (NAFLD) in 2020. Previous studies have shown that sex hormones are strongly linked to NAFLD development. This study aims to explore whether sex hormones are associated with MAFLD and liver fat content (LFC) in a middle-aged and elderly community. The study included 732 subjects aged 50-80 years enrolled from communities. MAFLD was diagnosed using the 2020 International Expert Consensus. LFC was calculated using parameters from abdominal ultrasound images. Serum estradiol (E2), total testosterone (TT), sex hormone-binding globulin (SHBG), FSH, and LH were measured by chemiluminescent microparticle immunoassay. MAFLD was diagnosed in 107/304 (35.2%) men and 154/428 (35.2%) women. After adjustments for confounding factors, logistic regression analysis showed that SHBG was negatively correlated with MAFLD in men (OR, 0.95 [0.93-0.97], p < 0.001). In women, SHBG and FSH were negatively correlated with MAFLD (OR, 0.95 [0.94-0.97], p < 0.001; OR, 0.97 [0.96-0.98], p < 0.001). Multivariate linear regression analysis showed that SHBG was a negative factor for LFC in both men (standardized ß = -0.188, p < 0.001) and women (standardized ß = -0.184, p < 0.001). FSH was a negative factor for LFC in women (standardized ß = -0.082, p = 0.046). SHBG was negatively correlated with MAFLD in middle-aged and elderly men and women. Moreover, FSH was negatively correlated, and bioactive testosterone was positively correlated with MAFLD in women. These findings suggest a relationship between sex hormones and MAFLD.

Neck Circumference Predicts the Occurrence and Remission of Metabolic Associated Fatty Liver Disease: A Longitudinal Study of Community-Dwelling Population.

AIM: Neck circumference (NC), a proxy for upper-body subcutaneous fat, is closely related to metabolic dysfunction, independent of other obesity indices. The purpose of this study was to explore the relationship between NC and the incidence and remission of metabolic associated fatty liver disease (MAFLD), a novel concept proposed by an international consensus panel in 2020 through a community-based longitudinal cohort. METHODS: This study included 1,549 community participants and was conducted from 2013 to 2016. MAFLD was diagnosed using the International Expert Consensus (2020) criteria. All participants underwent NC measurement and biochemical measurements. Elevated NC was defined as NC ≥38.5 cm in men and NC ≥34.5 cm in women. RESULTS: A total of 1,549 subjects (638 men and 911 women), with an average age of 59.6 ± 7.3 years, were included. During a mean follow-up of 2.1 years, MAFLD occurred in 146 of the 870 participants without baseline MAFLD and was resolved in 225 of the 679 participants with baseline MAFLD. After adjusting for confounding factors such as age, sex, body mass index, waist circumference, fasting plasma glucose, and liver enzyme levels, multivariable logistic regression showed that higher NC at baseline was positively correlated with MAFLD occurrence (OR 1.96, 95% confidence interval: 1.21-3.31; p = 0.003) and negatively correlated with MAFLD remission (OR 0.57, 95% confidence interval: 0.40-0.80; p < 0.001). CONCLUSION: A higher NC is associated with an increased risk of MAFLD occurrence and a reduced probability of MAFLD remission, making NC measurement a potential predictor in MAFLD management.

Neural mechanisms of inhibitory control deficits in obesity revealed by P3 but not N2 event-related potential component.

The lack of inhibitory control toward foods may cause unhealthy eating behavior and lead to obesity. However, previous research failed to reach consensus on the alterations in event-related potential (ERP) markers of inhibitory control, i.e., N2 and P3. We hypothesized that the ERP effects of inhibitory control reported in previous food-based Go/NoGo studies might be obscured by non-inhibitory processes associated with stimulus probability. We designed two food-based Go/NoGo tasks composed of stimuli with the same type and frequency of occurrence (60% non-foods, 20% high-calorie foods, 20% low-calorie foods), one with response inhibition toward high- and the other toward low-calorie foods. Such an experimental design allowed us to isolate neural activity associated with inhibitory control from that associated with non-inhibitory processes by constructing ERP difference waves between NoGo and Go trials with the same frequency of occurrence. Electroencephalography data were collected from 32 obese participants and 29 normal-weight controls. Obese participants showed significantly lower accuracy in NoGo trials than normal-weight controls in both tasks. ERP data suggested inhibition-related effects for P3 (P3d) but not N2 in the difference waves, and obese participants showed significantly decreased P3d amplitudes than normal-weight controls in both tasks. In addition, we found that across both groups, individuals with larger waist-to-hip ratios showed smaller P3d amplitudes in both tasks, while such correlations between body mass index and P3d amplitude were only observed in the high-calorie task. Our findings suggest that the decreased effect of P3, not N2, might reflect the neural substrate of inhibitory control deficits in obese people. Thus, P3 could serve as an important neural marker in the future development of new therapeutic strategy that aims to improve inhibitory control in obesity.

Evaluation of an mHealth-enabled hierarchical diabetes management intervention in primary care in China (ROADMAP): A cluster randomized trial.

BACKGROUND: Glycemic control remains suboptimal in developing countries due to critical system deficiencies. An innovative mobile health (mHealth)-enabled hierarchical diabetes management intervention was introduced and evaluated in China with the purpose of achieving better control of type 2 diabetes in primary care. METHODS AND FINDINGS: A community-based cluster randomized controlled trial was conducted among registered patients with type 2 diabetes in primary care from June 2017 to July 2019. A total of 19,601 participants were recruited from 864 communities (clusters) across 25 provinces in China, and 19,546 completed baseline assessment. Moreover, 576 communities (13,037 participants) were centrally randomized to the intervention and 288 communities (6,509 participants) to usual care. The intervention was centered on a tiered care team-delivered mHealth-mediated service package, initiated by monthly blood glucose monitoring at each structured clinic visit. Capacity building and quarterly performance review strategies upheld the quality of delivered primary care. The primary outcome was control of glycated hemoglobin (HbA1c; <7.0%), assessed at baseline and 12 months. The secondary outcomes include the individual/combined control rates of blood glucose, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C); changes in levels of HbA1c, BP, LDL-C, fasting blood glucose (FBG), and body weight; and episodes of hypoglycemia. Data were analyzed using intention-to-treat (ITT) generalized estimating equation (GEE) models, accounting for clustering and baseline values of the analyzed outcomes. After 1-year follow-up, 17,554 participants (89.8%) completed the end-of-study (EOS) assessment, with 45.1% of them from economically developed areas, 49.9% from urban areas, 60.5 (standard deviation [SD] 8.4) years of age, 41.2% male, 6.0 years of median diabetes duration, HbA1c level of 7.87% (SD 1.92%), and 37.3% with HbA1c <7.0% at baseline. Compared with usual care, the intervention led to an absolute improvement in the HbA1c control rate of 7.0% (95% confidence interval [CI] 4.0% to 10.0%) and a relative improvement of 18.6% (relative risk [RR] 1.186, 95% CI 1.105 to 1.267) and an absolute improvement in the composite ABC control (HbA1c <7.0%, BP <140/80 mm Hg, and LDL-C <2.6 mmol/L) rate of 1.9% (95% CI 0.5 to 3.5) and a relative improvement of 21.8% (RR 1.218, 95% CI 1.062 to 1.395). No difference was found on hypoglycemia episode and weight gain between groups. Study limitations include noncentralized laboratory tests except for HbA1c, and caution should be exercised when extrapolating the findings to patients not registered in primary care system. CONCLUSIONS: The mHealth-enabled hierarchical diabetes management intervention effectively improved diabetes control in primary care and has the potential to be transferred to other chronic conditions management in similar contexts. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) IOC-17011325.

A total weight loss of 25% shows better predictivity in evaluating the efficiency of bariatric surgery.

OBJECTIVES: The need for a unified definition of weight loss (WL) after bariatric surgery has recently been highlighted. We aimed to evaluate the reliability of two clinically common WL indications including percentage of total WL (%TWL) and percentage of excess WL (%EWL) through comparing their performances in predicting metabolic syndrome (MetS) remission 1 year after bariatric surgery. METHODS: A total of 430 individuals with obesity who underwent bariatric surgery were enrolled. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, MetS components and medications before and 1 year after surgery. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: The prevalence of MetS is 92.3% (397) at baseline. One year after bariatric surgery, 337 individuals (84.9%) were in MetS remission. The multivariate adjusted ORs were 1.16 (95% confidence interval [CI] 1.10-1.22) for each 1% increase in %TWL for MetS remission and 1.18 (95% CI 1.11-1.25) for each 5% increase in %EWL. This association with MetS remission remained statistically significant for %TWL after additional adjustment for %EWL (P for trend 0.029), and disappeared for %EWL. Receiver operating curve (ROC) analyses showed that the %TWL was more predictive than the %EWL (AUC%TWL vs. AUC%EWL, 0.749 vs. 0.700, p = 0.023). The Youden index indicated that the optimal %TWL cutoff point to identify MetS remission was 25%. CONCLUSIONS: We recommend that good responders to bariatric surgery should be defined as those exhibiting %TWL ≥ 25%.

Comparison of neck and waist circumferences for identifying subclinical atherosclerosis in a community-based population.

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.

Glucose-lowering pharmacotherapies in Chinese adults with type 2 diabetes and cardiovascular disease or chronic kidney disease. An expert consensus reported by the Chinese Diabetes Society and the Chinese Society of Endocrinology.

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.

Advanced glycation end products via skin autofluorescence as potential marker of carotid atherosclerosis in patients with type 2 diabetes.

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.

Correlations between neck circumference and serum thyroid hormones levels in postmenopausal women with euthyroid and subclinical hypothyroidism.

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.