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Multiple‐Input‐Multiple‐Output (MIMO) radar has the characteristic of multiple antenna channels, bringing on a big data volume for signal processing. Therefore, the trade‐off between detection ability and computational efficiency is always considered. In this article, an optimisation system is proposed to enhance the real‐time performance of frequency division MIMO radar without compromising accuracy. For the scenario of low‐altitude small target detection, a signal processing acceleration method is proposed and a MIMO radar optimisation system based on graphics processing unit (GPU) architecture is built. The signal model of frequency division MIMO radar is first established, improving the classical signal processing flow efficiency from the perspective of reducing fast Fourier transform (FFT) times and windowing operation times. To achieve an advanced acceleration, the parallel architecture of ArrayFire‐library in GPU is then employed. Distinct minimum parallel units are extracted by analysing the principle of digital beamforming (DBF), pulse compression, moving target detection (MTD), and constant false‐alarm rate (CFAR) algorithms. And the corresponding parallel algorithms are designed to constitute a parallel acceleration system of frequency division MIMO. Simulation results indicate that the proposed method significantly improves the efficiency of MIMO system with a maximum acceleration ratio of 65 times, meeting the real‐time processing requirements. [ABSTRACT FROM AUTHOR]

Introduction We evaluated the tolerability and efficacy of the addition of sitagliptin in Chinese patients with type 2 diabetes mellitus receiving stable insulin therapy alone or in combination with metformin. Materials and Methods A total of 467 patients with inadequate glycemic control on insulin (glycated hemoglobin [HbA1c] ≥7.5% and ≤11%) were randomized 1:1 to receive sitagliptin 100 mg once daily or a matching placebo for 24 weeks. Randomization was stratified based on metformin use (on or not on metformin) and type of insulin (pre-mixed vs intermediate-/long-acting) at screening. The primary end-point was the change from baseline at week 24 in HbA1c. Results The addition of sitagliptin led to a significantly ( P < 0.001) greater week 24 HbA1c reduction (0.7%) compared with the reduction (0.3%) with placebo. A significantly ( P = 0.013) greater proportion of patients taking sitagliptin (16%) had an HbA1c of <7.0% at week 24 compared with placebo (8%). The addition of sitagliptin significantly ( P < 0.001) reduced 2-h post-meal glucose by 26.5 mg/ dL (1.5 mmol/L) relative to placebo. Reductions from baseline in fasting plasma glucose were observed in both the sitagliptin (14.4 mg/ dL reduction) and placebo (10.7 mg/ dL reduction) groups; the between-group difference was not significant. A total of 64 (27.4%) patients taking sitagliptin and 51 (21.9%) taking placebo experienced adverse events of hypoglycemia (symptomatic or asymptomatic). Neither group had a significant change from baseline in bodyweight. Conclusions After 24 weeks, sitagliptin added to stable insulin therapy (±metformin) was generally well tolerated and improved glycemic control in Chinese patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

A joint communication jamming waveform is proposed in this study based on the FBMC- chirp. To increase the number of false targets in a single pulse period, the chirp signal is modulated to different subcarrier groups. Since the subcarriers of the FBMC-OQAM signal are orthogonal, the signals are naturally orthogonal. This allows the transmitter and receiver to be separated and achieve multiple false target jamming, allowing the CFAR threshold to be raised by about 20 dB and protecting the target from detection. The ratio of the frequency shift of the designed jamming signal to the frequency modulation depends on the delay time, making the joint signal more robust in response to jamming and resistant to frequency modulation. The use of intercepted radar signals allowed channel estimation, providing high-speed digital transmission while ensuring multi-false-target jamming. The simulation results show that the joint signal has jamming effects on the pulse Doppler radar. The proposed FBMC chirp joint waveform requires about 20 dB less jamming signal ratio than the existing method, and thus the energy saved can ensure the robust performance of the communication subsystem in the joint communication jamming system. The proposed system has excelled in communication rate and bit error rate performance, ensuring that instructions are accurately and completely transmitted while implementing effective jamming. [ABSTRACT FROM AUTHOR]

Since orthogonal frequency division multiplexing (OFDM) signals are sensitive to Doppler shift, OFDM signals with cyclic prefix (CP) not only reduce the communication rate but also result in symmetric pseudo peaks in the ambiguity function of the radar, which eventually lead to the degradation of the performance of the joint radar communication system (JRCS). In this study, a novel JRCS is proposed based on the filter bank multicarrier (FBMC) waveform for the inverse synthetic aperture radar (ISAR) imaging and communication system. On the one hand, FBMC waveforms are capable of low orthogonality between subcarriers, which can counter Doppler and multipath effects. On the other hand, FBMC waveforms do not require CP, so the false targets can be avoided and spectral efficiency can be improved. The influence of multipath effect and Doppler shift on FBMC waveform in an integrated system is analysed in detail, and a Doppler compensation algorithm suitable for FBMC‐integrated waveform is proposed. The phase error caused by target motion can be iteratively compensated to obtain a well‐focussed ISAR image. Finally, considering the ISAR image entropy after motion compensation as the evaluation metric, extensive simulation experiments verify the noise robustness and effectiveness of the proposed algorithm. Compared with the conventional OFDM and CP‐OFDM schemes, the simulation verifies that the proposed waveform design and processing method has better performance in the ISAR imaging and communication integrated system. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate the effect of high-sensitivity C-reactive protein (hs-CRP) on the risk of cardiovascular disease (CVD) in a Chinese population. A total of 2,656 participants (aged 30 to 95 years) with baseline hs-CRP levels available were monitored for the incidence of a composite of CVD events (stroke and coronary heart disease) during a 5.5-year period. With increasing quartiles of hs-CRP (<0.47, 0.47 to 0.97, 0.97 to 2.09, and ≥2.09 mg/L), the incidence of CVD increased progressively (11.7, 16.4, 24.7, and 36.5 per 1,000 person-years, respectively). In a Cox model adjusted for other traditional risk factors (e.g., age, blood pressure, diabetes mellitus, lipids, body mass index, smoking status), elevated hs-CRP (≥2.0 mg/L) independently predicted the risk of CVD (hazard ratio 1.39; 95% confidence interval 1.04 to 1.87). The effect was especially significant for stroke (hazard ratio 1.58; confidence interval 1.08 to 2.31). In conclusion, the results of our study suggest that elevated hs-CRP (≥2.0 mg/L) is an effective predictor of CVD in a Chinese population. [Copyright &y& Elsevier]

Abstract: Objective: To determine the appropriate cutoffs for visceral fat area (VFA) measured by magnetic resonance imaging linking to risk of the metabolic syndrome (MetS) and the corresponding waist circumference in Chinese. Methods and results: Totally 1140 individuals (men 525, women 615) aged from 35 to 75 years were included. The components of the MetS were defined by International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) definition, respectively. Receive operating characteristic curve analyses were used to determine the appropriate cutoffs of VFA and corresponding waist circumference in the prediction of the MetS. The optimal VFA cutoff was near 80cm2 in identifying the MetS with two or more components but not including overweight/obesity by either of the two definitions in all subjects. There was no difference in men by ages while women aged <50 years tended to have lower VFA cutoff than those aged ≥50 years by the two definitions. The appropriate waist circumference cutoffs were 90cm in men and 85cm in women for the MetS. Conclusion: The optimal cutoff of waist circumference for abdominal obesity is 90cm for men and 85cm for women in Chinese. [Copyright &y& Elsevier]

Aims: 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 nondiabetic population remains unknown. This study aimed to explore the extent of influence of sex hormones on HbA1c levels in nondiabetic population. Methods: A total of 1409 nondiabetic 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 = 0.003), and SHBG was inversely correlated with HbA1c (r = -0.125, P < 0.001) in women. Other hormones were not correlated with HbA1c (all P > 0.05). Multivariate linear regression analysis showed that, except for traditional factors, such as age, hemoglobin, and BMI, E2 was another determinant of HbA1c (standardized β = 0.137, P = 0.003) in men and the regression equation was HbA1c (%) = 0.001×E2 (pmol/ L) +5.465. In women, SHBG was another determinant of HbA1c (standardized β = -0.178, P < 0.001), except for age and systolic blood pressure (SBP), and the regression equation was HbA1c (%) = -0.002×SHBG (nmol)/L) +5.772. Conclusion: After controlling for confounding factors, E2 is positively correlated with HbA1c in men, and SHBG is inversely correlated with HbA1c in postmenopausal women. Sex hormones influence HbA1c levels in nondiabetic population, but it is very limited to affect the level of HbA1c in the diagnose of diabetes. Disclosure: Y. Bao: None. Y. Xu: None. W. Cao: None. Y. Shen: None. J. Tang: None. Y. Wang: None. X. Ma: None. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the agreement of different measurement methods of saliva 1,5-anhydroglucitol (1,5-AG) in different glucose metabolism populations. Methods: A total of 175 healthy volunteers (21–65 years, 58 males and 117 females) with normal glucose tolerance (NGT) and 80 diabetic patients (18–70 years, 44 males and 36 females) were enrolled from January 2018 to June 2019 and saliva was collected by saliva collection tube. Saliva 1,5-AG was measured using both enzymatic and mass spectrometry methods and serum 1,5-AG was determined by enzymatic method. Results: In subjects with NGT, the serum and saliva 1,5-AG levels detected by enzymatic method were both significantly positively correlated with the saliva 1,5-AG levels detected by liquid chromatography-mass spectrometry (LC-MS) (r = 0.247 and 0.523, respectively, both P < 0.05). However, there was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (r =-0.074, P = 0.333). In diabetic patients, the serum and saliva 1,5-AG levels detected by enzymatic method were both significantly positively correlated with the saliva 1,5-AG levels detected by gas chromatography-mass spectrometry (GC-MS) (r = 0.284 and 0.423, respectively, both P < 0.05). There was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (r ='0.079, P = 0.487). Conclusion: Both the serum and saliva 1,5-AG levels detected by enzymatic method have good agreement with saliva 1,5-AG levels detected by mass spectrometry method. The saliva and serum 1,5-AG levels detected by enzymatic method are not well correlated, so the enzymatic detection of saliva 1,5-AG needs further improvement for clinical practice. Disclosure: Y. Bao: None. C. Jian: None. A. Zhao: None. X. Ma: None. W. Lu: None. W. Zhu: None. Y. Wang: None. J. Zhou: None. [ABSTRACT FROM AUTHOR]

Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is involved in lipid and glucose metabolism via mRNA processing. However, whether and how HNRNPA1 alters adipocyte function in obesity remain obscure. Here, we found that the obese state downregulated HNRNPA1 expression in white adipose tissue (WAT). The depletion of adipocyte HNRNPA1 promoted markedly increased macrophage infiltration and expression of proinflammatory and fibrosis genes in WAT of obese mice, eventually leading to exacerbated insulin sensitivity, glucose tolerance, and hepatic steatosis. Mechanistically, HNRNPA1 interacted with Ccl2 and regulated its mRNA stability. Intraperitoneal injection of CCL2-CCR2 signaling antagonist improved adipose tissue inflammation and systemic glucose homeostasis. Furthermore, HNRNPA1 expression in human WAT was negatively correlated with BMI, fat percentage, and subcutaneous fat area. Among individuals with 1-year metabolic surgery follow-up, HNRNPA1 expression was positively related to percentage of total weight loss. These findings identify adipocyte HNRNPA1 as a link between adipose tissue inflammation and systemic metabolic homeostasis, which might be a promising therapeutic target for obesity-related disorders. Article Highlights: Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is decreased during obesity, but the specific role in adipose tissue remains unclear. Adipocyte-specific depletion of Hnrnpa1 accelerates adipose tissue inflammation and systemic metabolic disorders via enhancing mRNA stability of chemokine CCL2. CCL2 receptor antagonist rescues metabolic dysfunction elicited by Hnrnpa1 depletion. HNRNPA1 expression in human adipose tissue is closely related to BMI, fat percentage, and subcutaneous fat area and is positively associated with percentage of total weight loss 1 year after bariatric surgery. [ABSTRACT FROM AUTHOR]

Context: Unlike other commonly used invasive blood glucose monitoring methods, saliva detection prevents patients from suffering the physical uneasiness. Serum 1,5-anhydroglucitol (1,5-AG) is a new indicator for assessing short-term glycemic control. However, there are currently few studies on saliva 1,5-AG in diabetes mellitus (DM). Objective: This study aimed to evaluate the effectiveness of saliva 1,5-AG in diabetes screening in a Chinese population. Design and Participants: A total of 641 subjects without a valid diabetic history (251 men and 390 women) were recruited from September 2018 to June 2019 and underwent an oral glucose tolerance test (OGTT). Fasting saliva 1,5-AG (1,5-AG0) and postload 2-hour saliva 1,5-AG (1,5-AG120) were measured with liquid chromatography-mass spectrometry. Serum 1,5-AG0 and 1,5-AG120 were measured with enzymatic method. Results: Saliva 1,5-AG levels in DM subjects were lower than those in nondiabetes mellitus subjects (both P < 0.05). Saliva 1,5-AG was positively correlated with serum 1,5-AG and negatively correlated with blood glucose and glycated hemoglobin (HbA1c) (all P < 0.05). The optimal cutoff points of saliva 1,5-AG0 and 1,5-AG120 for diabetes screening were 0.436 μg/mL and 0.438 μg/mL, respectively. Fasting plasma glucose (FPG) combined with saliva 1,5-AG0 and HbA1c combined with saliva 1,5-AG120 reduced the proportion of people who required an OGTT by 47.22% and 51.41% compared with FPG alone and HbA1c combined with FPG, respectively. Conclusion: The optimal cutoff point of saliva 1,5-AG for diabetes screening was 0.44 μg/mL. Saliva 1,5-AG combined with FPG or HbA1c improved the efficiency of diabetes screening. Saliva 1,5-AG is robust in nonfasting measurements and a noninvasive and convenient tool for diabetes screening. Disclosure: Y. Bao: None. C. Jian: None. A. Zhao: None. X. Ma: None. K. Ge: None. W. Lu: None. W. Zhu: None. Y. Wang: None. J. Zhou: None. W. Jia: None. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), is the only proven means of sustained weight loss and type diabetes mellitus (T2DM) remission/control but data are limited in China. Method: Patients underwent laparoscopic RYGB or SG at 6 Chinese sites from Aug 2014 to Jan 2016 and returned for follow-up regularly after surgery. We evaluated the impact on a composite measure of glycemic control, which was defined as Complete Remission: HbA1c < 6% and FPG < 5.6 mmol/L for 1 year absent antidiabetic medications; Partial Remission: HbA1c 6 - 6.4% and FPG 5.6 - 6.9 mmol/L for 1 year absent antidiabetic medications; Improvement: Reduction in HbA1c (> 1%) or FPG (>1.4 mmol/L) or reduction accompanied by a decrease in antidiabetic medication for at least 1 year; Unchanged: Absence of remission or improvement; Recurrence: HbA1c or FPG in the diabetic range or need for antidiabetic medication after initial remission. Results: There were 101 procedures completed. The mean (±SD) age of the patients was 37.1±9.7 years, and 52% were women. The mean BMI was 35.0±5.0 and mean HbA1c was 8.1±1.7% at baseline. Outcomes at 2-year follow-up were available for 80 patients (63 RYGB and 17 SG) and showed substantial improvements. Complete or partial remission at 2 years was achieved in at least 83% of patients in two groups (33 [53.2%] and19 [30.6%] in RYGB; 12 [70.6%] and 3 [17.6%] in SG), less than 5% were unchanged and recurrence was not seen in either group. There was a significant reduction in HbA1c from baseline in both RYGB and SG (-2.4 ± 1.8% [P>0.001] and -2.1 ± 1.8% [P>0.001]). Concurrent significant improvements in cardiometabolic parameters such as triglycerides and blood pressure, and reductions in antidiabetic medication usage were also observed. Conclusion: The 2 years data demonstrate a clinically meaningful impact on a composite measure of glycemic control with a majority of patients demonstrating complete remission of T2DM in both groups. Disclosure: Y. Bao: None. H. Liang: None. P. Zhang: None. C. Wang: None. T. Jiang: None. N. Zhang: None. J. Zhu: None. H. Yu: None. J. Han: None. S. Lin: None. J. Yang: None. W. Yang: None. S. Chen: None. D. Du: None. Y. Ma: None. E.J. Fegelman: Employee; Self; Ethicon US, LLC. M. Schwiers: Employee; Self; Ethicon, Inc. J. Waggoner: Employee; Self; Ethicon, Inc. T. Yang: Employee; Self; Johnson & Johnson Medical Devices Companies. R. Zhang: None. W. Jia: None. Funding: Ethicon Inc. [ABSTRACT FROM AUTHOR]

Aims: This study was designed to investigate the interrelationships between three bone-derived factors [serum osteocalcin (OCN), fibroblast growth factor (FGF) 23, and neutrophil gelatinase-associated lipocalin (NGAL) levels] and body fat content and distribution, in order to reveal the potential endocrine function of bone in the development of obesity. Methods: We recruited 1179 people (aged 59.5 ± 6.2 years) from communities in Shanghai. Serum OCN levels were determined using an electrochemiluminescence immunoassay, and thus serum FGF-23 and NGAL levels were determined using a sandwich enzyme-linked immunosorbent assay. The abdominal fat distribution, including visceral fat area (VFA), was assessed by magnetic resonance imaging. Visceral obesity was defined as a VFA ≥ 80 cm2. Results: Serum OCN levels were inversely correlated with body fat parameters, while FGF-23 and NGAL were positively correlated (P < 0.05). After adjusting for confounders, waist circumference (W) and VFA had a closer relationship with serum OCN, FGF-23, and NGAL levels than body mass index (BMI) and body fat percentage (fat%, all P < 0.05). The risk of visceral obesity significantly increased with higher FGF-23 and/or NGAL levels, as well as with reduced OCN levels (all P < 0.05). In addition, serum OCN, FGF-23, and NGAL levels were independently associated with visceral obesity (all P < 0.01). The relationships persisted among subjects with normal glucose tolerance or subjects with hyperglycaemia (both P < 0.05). Conclusions: Compared to overall adiposity, visceral adiposity was more closely related to serum OCN, FGF-23 and NGAL levels. There was no interaction among the relationship of three bone-derived factors with visceral obesity, which suggested the independent relationship of endocrine function of skeleton with body fat. Disclosure: Y. Bao: None. Y. Xu: None. X. Ma: None. X. Pan: None. X. He: None. Y. Xiao: None. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Low muscle mass is a novel and effective predictive marker for incidence of cardiovascular events in a general population. • This relationship is independent of multiple well-established CVD risk factors such as smoking, diabetes, hypertension, and dyslipidemia. • Low muscle mass strengthens predicting future cardiovascular events over traditional risk score, especially among people with a moderate-to-high risk. We aimed to explore the association between skeletal muscle mass and cardiovascular events, and its additional value on the assessment of cardiovascular diseases (CVD) over traditional risk scores. The study included 1365 community-based participants aged over 50 years and free of CVDs at baseline. Participants completed detailed assessments at baseline and received a follow-up assessment in 2021–2022 via phone calls or electronic medical records. Skeletal muscle mass was measured using an automatic bioelectric analyzer. Predicted probabilities of 10-year atherosclerotic cardiovascular disease (ASCVD) risk were estimated individually with the China-PAR equation. After a mean follow-up of 7.6 years, 144 cardiovascular events were identified. The fully-adjusted hazard ratios (HRs) of cardiovascular events were 0.93 (0.88–0.98) and 1.08 (1.04–1.12) for skeletal muscle mass and predicted 10-year risk, respectively. Among participants over 60 years and with two or more risk factors, cardiovascular events risk increased progressively with each decreasing skeletal muscle tertile. Receiver operating characteristic curves showed that the C-statistic of predicting cardiovascular events for a 10-year risk assessment was slightly increased after adding skeletal muscle mass. The categorical net reclassification improvement (NRI) showed a 56.7% increase in the reclassification. The continuous NRI and integrated discrimination improvement increased as well. Participants with low skeletal muscle mass were more likely to have cardiovascular events. Low muscle mass improved the predictive power of CVD incidence over the original risk score, indicating that muscle mass could be a valuable parameter and a declining value needed early detection in the population. [ABSTRACT FROM AUTHOR]

Background: Serum cholinesterase (ChE) is positively associated with incident diabetes and dyslipidemia. We aimed to investigate the relationship between ChE and the incidence of diabetic retinopathy (DR). Methods: Based on a community-based cohort study followed for 4.6 years, 1133 participants aged 55–70 years with diabetes were analyzed. Fundus photographs were taken for each eye at both baseline and follow-up investigations. The presence and severity of DR were categorized into no DR, mild non-proliferative DR (NPDR), and referable DR (moderate NPDR or worse). Binary and multinomial logistic regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) between ChE and DR. Results: Among the 1133 participants, 72 (6.4%) cases of DR occurred. The multivariable binary logistic regression showed that the highest tertile of ChE (≥ 422 U/L) was associated with a 2.01-fold higher risk of incident DR (RR 2.01, 95%CI 1.01-4.00; P for trend < 0.05) than the lowest tertile (< 354 U/L). The multivariable binary and multinomial logistic regression showed that the risk of DR increased by 41% (RR 1.41, 95%CI 1.05–1.90), and the risk of incident referable DR was almost 2-fold higher than no DR (RR 1.99, 95%CI 1.24–3.18) with per 1-SD increase of loge-transformed ChE. Furthermore, multiplicative interactions were found between ChE and elderly participants (aged 60 and older; P for interaction = 0.003) and men (P for interaction = 0.044) on the risk of DR. Conclusions: In this study, ChE was associated with the incidence of DR, especially referable DR. ChE was a potential biomarker for predicting the incident DR. [ABSTRACT FROM AUTHOR]

Background: Low muscle mass likely results in reduced capacity for glucose disposal, leading to a significant but under-appreciated contribution to increasing the risk of diabetes. But few prospective studies have investigated the association between the loss of muscle mass and the occurrence of diabetes. We aimed to investigate whether short-term changes in muscle mass affect the incidence of diabetes in a Chinese population. Methods: This study included 1275 individuals without evident diabetes at baseline. In the baseline and re-examination, individuals completed the risk factors survey and underwent body composition measurement. Muscle mass index was defined as the percentage skeletal muscle mass, which was measured by an automatic bioelectric analyzer. Results: After a median follow-up of 2.1 years, 142 individuals developed diabetes (11.1%). There was an inverse association between basal skeletal muscle mass index and the risk of diabetes in participants with impaired glucose regulation but not in those with normal glucose tolerance. Multivariate-adjusted hazard ratios for the risk of developing diabetes were 0.85 (95% CI: 0.74–0.98) and 1.15 (95% CI: 0.98–1.34), respectively. Furthermore, Cox regression analysis revealed that a two-year change in skeletal muscle mass was also inversely associated with the incidence of diabetes in both participants with normal glucose tolerance and with impaired glucose regulation (HR: 0.76, 95% CI: 0.65–0.89; HR: 0.81, 95% CI: 0.71–0.91). Conclusions: These findings emphasized the importance of early detection and control of muscle mass loss for the prevention of diabetes. [ABSTRACT FROM AUTHOR]

Background: The risk of cardiovascular diseases has rapidly increased among middle-aged and elderly. However, little is known about the relationship of body composition changes with the risk of cardiovascular events among this population in China. We explored the associations of 2-year changes in fat percentage (fat%) and fat-free mass percentage (FFM%) with subsequent cardiovascular events in a middle-aged and elderly community-based cohort. Methods: This study included 1048 participants (456 men [43.51%], aged 50–80 years) without overt cardiovascular disease, who underwent two examinations during 2013–2014 and 2015–2016. All participants were followed up until 2022 for cardiovascular events. A bioelectrical impedance analyzer was used to calculate fat% and FFM% change. Results: At baseline, the median body mass index (BMI), fat%, and FFM% were 23.9 (22.1–25.9) kg/m2, 27.2 (20.8–33.6)%, and 72.8 (66.4–79.2)%, respectively. Two-year changes in fat% and FFM% were 0.31 (− 5.53 to 6.87)% and − 0.12 (− 2.36 to 2.06)%. During an average follow-up of 5.5 years, 86 cardiovascular events (8.21%) occurred. Cox regression models showed that hazard ratios (HRs) of every 2% change in fat% and FFM% for cardiovascular events were 1.04 (95% confidence interval [CI] 1.01–1.07) and 0.84 (95% CI 0.74–0.95), respectively. Compared with participants with stable fat% (–2% ≤ ⊿fat% < 2%), those with fat% gain ≥ 2% had an increased risk of cardiovascular events (HR 2.07, 95% CI 1.08–3.97). FFM% loss > 8% was associated with a higher risk of cardiovascular events (HR 3.83, 95% CI 1.29–11.4). Conclusions: In a middle-aged and elderly community-based Chinese population, fat% gain or FFM% loss was associated with an increased risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

To assess the role of body fat and serum C-reactive protein (CRP) level in the prediction of cardiovascular events among individuals from Shanghai communities. A total of 5502 individuals aged over 20 years from 1998 to 2001 in two communities of Shanghai were included. In this cohort 2790 individuals aged over 30 years underwent a five year follow-up. Logistic regression model was used to estimate the relationship between CRP level and the risk of metabolic syndrome (MS). Receiver operating characteristic curve was used to find out the best cut-point for body mass index (BMI) and waist circumference (W) to assess MS defined as Chinese Diabetes Society (2004) working definition. Our data showed: 1.Compared with those subjects in the lowest quartile, individuals in the highest quartile of CRP level (men 2.11 mg/L, women 2.22mg/L) had increased risk of MS(10 times in men, 8.5 times in women) at baseline. 2.The best cut-point for BMI in assessing MS was 25kg/m² in both men and women, and for W was 85cm in men and 80cm in women at baseline. 3.Compared with the subgroup of BMI<25 kg/m² with CRP<2 mg/L, the relative risk of cardiovascular events was as following: 1.98 in the subgroup of BMI≥25kg/m² with CRP<2mg/L,1.55 in the subgroup of BMI<25kg/m² with CRP≥2mg/L and 2.26 in the subgroup of BMI≥25kg/m² with CRP≥2mg/L. 4.Compared with the subgroup of W<85cm with CRP<2 mg/L in men and W<80cm with CRP<2 mg/L in women, the relative risk of cardiovascular events was as following: in men 1.83 in the subgroup of W≥85cm with CRP<2mg/L, 1.15 in the subgroup of W<85cm with CRP≥2mg/L and 2.34 in the subgroup of W≥85cm with CRP≥2mg/L; and in women 1.61 in the subgroup of W≥80cm with CRP<2mg/L, 1.25 in the subgroup of W<80cm with CRP≥2mg/L and 2.21 in the subgroup of W≥80cm with CRP≥2mg/L. In conclusion, 1.The risk of MS was dramatically increased in subjects with CRP level above 2mg/L. 2.To determine MS the optimal cut-point for BMI was 25kg/m² and for W was 85cm in men and 80cm in women. 3. In a five year follow-up study, the risk of cardiovascular events was significantly elevated not only in individuals with BMI over 25kg/m² but also in men with W over 85cm and in women with W over 80cm independent of CRP level. The risk of cardio vascular events was further increased in subjects with elevated CRP level combined with either higher BMI or W. [ABSTRACT FROM AUTHOR]

[Display omitted] Ultra rapid lispro (URLi) is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal, with the aim of improving postprandial glucose (PPG) control. We conducted a multinational, multicenter, randomized, double-blind, treat-to-target, 26-week, phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes (T2D). After an 8-week lead-in period during which basal insulin glargine or degludec was optimized, adults with T2D were randomized (2:1) to prandial URLi (n = 395) or lispro (n = 200). The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c (HbA 1c) change from baseline to week 26. Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1- and 2-h PPG excursions during a mixed-meal tolerance test (MMTT) and HbA 1c change at week 26. URLi showed non-inferiority for HbA 1c change at week 26 versus lispro (least-squares mean [LSM] difference, 0.07%; 95% confidence interval: −0.07, 0.21). HbA 1c was reduced by 0.56% and 0.63% with URLi and lispro, respectively, with no significant treatment difference (P = 0.321). URLi provided superior PPG excursion control versus lispro at 1 h (LSM difference: −14.6 mg/dL, P < 0.001) and 2 h (LSM difference: −21.8 mg/dL, P < 0.001) as well as other time points (30–240 min) during the MMTT. Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro. The safety profiles were generally similar between treatment groups. In conclusion, URLi was superior to lispro for PPG control, with non-inferiority in HbA 1c improvement, in adults with T2D. [ABSTRACT FROM AUTHOR]

Aims/introduction: We proposed a novel continuous glucose monitoring (CGM)‐based metric, area under the curve in range (AucIR), for integrating both the amplitude and duration of dysglycemia, and further compared AucIR with the emerging key CGM‐derived metric, time in range (TIR). Materials and methods: A total of 2,030 adult patients with type 2 diabetes were enrolled during May 2020 to October 2021. AucIR and TIR were measured with 7‐day CGM data. Logistic regression analysis and the C‐statistic was carried out to assess the association of AucIR and TIR with diabetic retinopathy (DR). Results: Both AucIR (r = −0.89) and TIR (r = −0.95) were strongly correlated with mean glucose levels. Compared with TIR, AucIR showed a tighter relationship with parameters of glycemic variability, including the coefficient of variation (r = −0.56), standard deviation (r = −0.89) and mean amplitude of glycemic excursions (r = −0.70). For each absolute 10% decrease in AucIR, the risk of DR was increased by 7% (95% confidence interval 1.02–1.13) after adjustment for confounders. With respect to TIR, each absolute 10% decrease was associated with an 8% (95% confidence interval 1.03–1.14) increased risk of DR. The model discrimination for DR, as measured by C‐statistic, did not differ significantly between the two metrics (P > 0.05). Conclusions: AucIR did not provide added benefit over TIR in the assessment of DR risk among patients with type 2 diabetes. The potential value of AucIR needs to be explored in future studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between disposition index (DI) and the risk of adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). Methods A total of 1 912 women were prospectively recruited from January 2015 to December 2017 in Department of Gynecology and Obstetrics of the Shanghai Jiao Tong University of Medicine Affiliated Sixth People's Hospital. According to whether they had GDM, they were divided into GDM group (434 cases) and non-GDM group (1 478 cases). All participants received a 75 g oral glucose tolerance test (OGTT) during the 24-28 gestational weeks and complete basal and delivery information was collected. The insulin sensitivity index (ISI) and the area under the insulin curve/area under the blood glucose curve (AUCINS120/AUCGLU120) were calculated from the results of the 75 g OGTT. The DI was calculated as the product of the ISI and AUCINS120/AUCGLU120 and then log transformed. Adverse pregnancy outcomes were defined as large for gestational age (LGA), primary cesarean section, preeclampsia, and preterm birth. Comparison between groups was performed by t test, Wilcoxon rank sum test and χ² test. Logistic regression analysis was used to explore the relationship between DI and the risk of adverse pregnancy outcomes. Results Women with GDM had a lower ISI even DI than women without GDM. Compared with women with GDM in the lowest quartile (Q1, DI<2.90) of DI, multivariable adjusted (age, body mass index, other pregnancy complications, gestational age at the time of OGTT, fetal sex and parity) odds ratios (OR) of adverse pregnancy outcomes of those in the second (Q2, DI 2.90-3.02), third (Q3, DI 3.03-3.16), and highest (Q4, DI>3.16) quartiles of DI were reduced by 55% (95%CI 0.23-0.87), 34% (95%CI 0.35-1.25), and 59% (95%CI 0.24-0.71) (P for trend=0.01), respectively. When DI was considered as a continuous variable, the multivariable adjusted OR of adverse pregnancy outcomes in women with GDM was reduced by 60% (95%CI 0.21-0.73) for each one unit increase in DI. However, DI was not associated with adverse pregnancy outcomes in women without GDM (OR=0.66, 95%CI 0.36-1.18). Conclusion Elevated DI levels in women with GDM are closely associated with a reduced risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

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. [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]

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 β = 0.137, P =.003) in men; besides, in women, SHBG was another determinant of HbA1c (standardized β = − 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. [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]

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]

A-FABP (adipocyte fatty acid-binding protein), one of the most abundant proteins in adipocytes, plays a key role in obesity-related insulin resistance, inflammation and atherosclerosis in animals. In the present study, we sought to investigate the association of A-FABP with HF (heart failure) in Chinese subjects. Serum A-FABP levels were measured in 252 HF patients and 261 age-, gender- and BMI (body mass index)-matched non-HF subjects. Echocardiography was performed on each patient. The severity of HF was determined by the NYHA (New York Heart Association) classification system. After adjustments for age, gender and BMI, serum A-FABP concentrations in patients with HF were significantly higher than in non-HF patients [11.17 (6.63-19.93) ng/ml compared with 5.67 (3.20-8.87) ng/ml; P<0.001] and significantly progressed with the NYHA class (P<0.001). In addition, NT-proBNP (N-terminal pro-brain natriuretic peptide) was independently and positively correlated with A-FABP (standardized ß =0.340, P<0.001) after adjusting for confounding factors. Each echocardiographic parameter, especially LVEF (left ventricular ejection fraction), was independently associated with A-FABP (all P<0.05). Multivariate logistic regression analysis demonstrated that A-FABP concentration was an independent risk factor for HF [odds ratio, 6.93 (95% confidence interval, 2.49-19.30); P<0.001]. Our results demonstrate that A-FABP is closely associated with HF, and raise the possibility that increased A-FABP may be causally related to the pathogenesis of heart dysfunction in humans. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Abstract: Background: Whether metabolic syndrome (MetS) could serve as a valid indicator for cardiovascular disease (CVD) is in controversy. The aim of the study was to prospectively evaluate the predictive value of the MetS for CVD events in Chinese population by different MetS definitions. Methods: This was a community-based cohort study. MetS was defined according to the World Health Organization (WHO), the International Diabetes Federation (IDF), the National Cholesterol Education Program Adult Treatment Panel III (NCEPIII) and Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG), respectively. 2788 subjects were included. The incidence of CVD events was monitored during a 5.5-year period. Results: The proportion of MetS defined by the WHO, IDF, NCEPIII and JCDCG criteria was 25.9%, 15.4%, 22.0% and 26.1%, respectively in men, and 24.5%, 28.0%, 31.1% and 23.0%, respectively in women. After adjusting for age, all four definitions were associated with increased risk of CVD events in women, but not in men. The corresponding hazard ratios (HRs) [95% confidence intervals (CIs)] in women were 2.13 (1.44–3.16), 1.49 (1.01–2.19), 1.50 (1.02–2.21) and 2.10 (1.41–3.11). The HRs remained significant with WHO and JCDCG definitions, not with the IDF and NCEPIII definitions, when factors of LDL cholesterol, and smoking were adjusted. Conclusion: The MetS by the WHO and JCDCG definition was associated with increased risk of CVD events in Chinese women after adjustment for age, total cholesterol, LDL cholesterol, and smoking. [Copyright &y& Elsevier]

Abstract: Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0±8.9μg/ml vs. 41.3±9.8μg/ml, p <0.001), while adiponectin decreased (17.4±9.3μg/ml vs. 13.8±7.0μg/ml, p =0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5±9.9μg/ml vs. 34.0±10.7μg/ml, p =0.031 and 12.7±5.7μg/ml vs. 20.23±9.8μg/ml, p <0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease. [Copyright &y& Elsevier]

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. [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]

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]

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]

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]

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]

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]

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]

We investigated the real-world incidence of hypoglycemic events among patients with type 1 or type 2 diabetes (T1DM or T2DM) receiving insulin in routine clinical practice in China. In this observational study, data were collected electronically via the Lilly Connected Care Program (LCCP) electronic system from adults with T1DM or T2DM who had registered on LCCP between 1 February 2019 and 31 January 2022, had used insulin for a full 12-week period following registration. The following outcomes were assessed during the 12 weeks following registration: incidence of level 1 and level 2 hypoglycemia. In total, 22,752 patients were enrolled. Among patients with monitoring data, over the 12-week study period, level 1 and 2 hypoglycemia were experienced by 48.8% and 25.9% of patients with T1DM and 26.5% and 13.9% of patients with T2DM. The proportion of patients treated with oral anti-diabetes drugs (OADs) capable of producing hypoglycemia (sulfonylurea or glinide) was 1.3% in T1DM and 1.6% in T2DM, respectively. Questionnaire data revealed that up to 92.5% of hypoglycemic events occurred outside of hospital and 18.6% were serious. These real-world data collected from Chinese patients with diabetes receiving insulin treatment reveal a relatively high percentage of patients experiencing hypoglycemia, with around one quarter of these events classified as severe and as many as 92.5% occurring outside of a hospital or clinic. [ABSTRACT FROM AUTHOR]

[Display omitted] • Serum neutrophil gelatinase associated lipocalin (NGAL) determined at baseline predicted the development of major adverse cardiovascular events (MACE) in women. • Visceral fat area (VFA) modified the relationship between serum NGAL and MACE in women, strengthening the association at relatively low VFA levels. • Elevated serum NGAL can be used as an early indicator of metabolic disorders in women, eventually leading to the occurrence of MACE. We assessed the predictive values of neutrophil gelatinase-associated lipocalin (NGAL), fat distribution, and their interaction on the development of major adverse cardiovascular events (MACE) in a community-based cohort of middle-aged and older individuals. This prospective study involved 1349 adults (43.2% men) aged 50–80 y, without baseline cardiovascular diseases, from communities in 2013–2014. All participants were followed up for a mean of 7.6 y via phone calls and medical records. Serum NGAL concentrations were analyzed at baseline. Fat distribution, including subcutaneous fat area and visceral fat area (VFA), was assessed by magnetic resonance imaging. In fully-adjusted Cox regression models, baseline high NGAL concentrations were related to an increased risk of MACE in women [HR 1.75, 95% CI 1.03–2.99], compared with low NGAL concentrations. After stratification by VFA concentrations, the observed association was more predominant in women with baseline low VFA (HR 1.24, 95% CI 1.11–1.38). Moreover, the association between NGAL and MACE was interacted by VFA, strengthening the association at low VFA concentrations (P interaction < 0.05). Serum NGAL determined at baseline predicts the development of MACE, and the association is modified by VFA in women. [ABSTRACT FROM AUTHOR]

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]

Background: The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of lower extremity atherosclerotic disease (LEAD). Method: We performed a prospective cohort study of 436 patients with type 2 diabetes (258 men and 178 women) with at least 3 measurements of HbA1c and GA prior to baseline investigation from the Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital. Different HbA1c and GA variability markers were calculated. Multivariable Cox proportional hazard regression models were used to demonstrate the association between visit-to-visit HbA1c and GA variability and the risk of incident or progressive LEAD. Results: During a mean follow-up period of 3.77 years, 112 participants developed LEAD. Multivariate-adjusted hazard ratios (HRs) of LEAD across tertiles of GA-CV values were 1.00, 1.06 (95% confidence interval [CI] 0.65–1.75), and 1.71 (95% CI 1.07–2.73) (P for trend = 0.042), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of LEAD primary were found. Multivariate-adjusted HRs of LEAD for each 1 unit increase in GA-CV, GA-VIM and GA-ARV were 1.03 (95% CI 1.01–1.06), 1.32 (95% CI 1.03–1.69), and 1.07 (95%CI 1.01–1.15), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of LEAD. Conclusions: Visit-to-visit variability of GA may be an optimal biomarker in relation to LEAD risk among patients with type 2 diabetes. [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]

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]

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]