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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]

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]

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]

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]

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]

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]

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]

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]

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]

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

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

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

Background: Clinical and basic investigations have indicated a significant association between circulating growth differentiation factor 15 (GDF15) and cardiovascular disease; however, the relationship between GDF15 and lower extremity atherosclerotic disease (LEAD) has been less studied. The present study aimed to explore the association between GDF15 and LEAD in Chinese patients with type 2 diabetes mellitus (T2DM). Considering that obesity is an important factor associated with circulating GDF15 levels, whether the relationship between serum GDF15 levels and LEAD is affected by body mass index (BMI) was also analysed. Methods: A total of 376 hospitalized T2DM patients were enrolled (161 with LEAD and 215 without LEAD). A sandwich enzyme-linked immunosorbent assay was used to detect the serum GDF15 levels. The femoral intima-media thickness (F-IMT) and LEAD were assessed by ultrasonography. Results: Patients with LEAD had significantly higher serum GDF15 levels than those without LEAD, regardless of whether their BMI was < 25 kg/m2 or ≥ 25 kg/m2 (both P < 0.05). Serum GDF15 levels were independently positively related to the F-IMT (standardized β = 0.162, P = 0.002). After adjusting for confounding factors, per 1-standard deviation (SD) increase in the serum GDF15 levels was significantly related to an approximately 1.4-fold increased risk of LEAD in the total population (P < 0.05). Regardless of whether the BMI was < 25 kg/m2 or ≥ 25 kg/m2, this association remained significant, with approximately 1.6- and 1.4-fold increased risks of LEAD, respectively (both P < 0.05). Conclusions: High serum GDF15 levels were significantly correlated with an increased risk of LEAD in T2DM patients, and this relationship was independent of BMI. [ABSTRACT FROM AUTHOR]

Background. Fulminant type 1 diabetes mellitus (FT1DM) onsets abruptly and usually occurs within 1 week after the onset of hyperglycemic symptoms. Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) are indicators that reflect short-term glucose levels. This study was aimed at investigating whether the 1,5-AG/GA index (AGI) is a suitable indicator for early FT1DM identification. Methods. A total of 226 subjects were enrolled, all with glycated hemoglobin A 1 c Hb A 1 c < 8.7 %. FT1DM was diagnosed based on the 2012 Japan Diabetes Society criteria. Results. The AGI level was 0.54 (0.17–1.36) in the whole group. It was lower in FT1DM patients (0.16 [0.10–0.25]). Among the participants whose HbA1c did not exceed 7.0%, the AGI of FT1DM decreased significantly compared to type 1A diabetes (T1ADM) and latent autoimmune diabetes in adults (LADA) patients (0.16 [0.12–0.26] vs. 0.46 [0.24–0.72] vs. 0.31 [0.19–0.43], both P < 0.05). The receiver operating characteristic (ROC) curve showed that AGI can be used to distinguish FT1DM and T1ADM patients with Hb A 1 c < 8.7 %. Diagnosing FT1DM based on AGI ≤ 0.3 only can help narrow down suspected FT1DM by up to 26.87%. If we diagnosed FT1DM when AGI was ≤0.3 and HbA1c was ≤7.0%, the success rate further increased to 86.57%, among which 85.00% of FT1DM and 87.23% of T1ADM patients were successfully identified. Therefore, using the combination criteria of AGI and HbA1c would improve the differential diagnosis efficacy by 61.11% compared with the AGI criterion only. Conclusion. AGI can help facilitate the early differential diagnosis of FT1DM and T1ADM when Hb A 1 c < 8.7 % , with an optimal cut-off point of 0.3. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic foot ulcers develop with deviations in the distribution of plantar pressure. It is difficult to interpret any alteration in plantar pressure under different conditions of type 2 diabetes mellitus (T2DM). The aim of this study was to gain a better insight into the variations in plantar pressure with increased duration of diabetes. Methods: Plantar pressure was examined in 1196 participants with or without T2DM. Subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) were assigned to control groups, and those with T2DM were divided into five groups according to diabetes duration (< 2 years, 2–5 years, 5–10 years, 10–15 years, and > 15 years). The clinical characteristics, plantar peak pressure, and pressure–time integral (PTI) were compared among the seven study groups, and factors associated with peak pressure and the PTI were analyzed. Results: At the hallux, peak pressure exhibited an upward trend in patients with T2DM within 5 years of diabetes duration, followed by a distinct downward slope with further progression of the disease (trend analysis, p < 0.05). An uneven distribution of peak pressure was found at other locations, but this unevenness was ultimately lower than that in the two control groups (p < 0.05). No obvious trend was noted for PTI among patients with different diabetes duration; however, those with diabetes for > 10 years manifested a significantly sharper increase in the PTI at the metatarsus (11.63 Ns/cm2, p < 0.05) and heel (14.12 Ns/cm2, p < 0.05) than at the hallux (8.76 Ns/cm2). A fluctuation in the PTI was also detected at the hallux and midfoot of diabetes patients, which was broadly flat when compared with that of the two control groups. The stepwise multiple regression analysis revealed that the variation in plantar pressure was independently associated with age, body mass index, and vibration perception threshold (VPT) (p < 0.05). Conclusions: There would appear to be an association between longer diabetes duration and decreased peak pressure for the hallux, suggesting that individuals with diabetes for > 10 years will have an increased PTI for the metatarsus and heel. The reduced pressure on the hallux is believed to be transferred to the metatarsus. Age, BMI, and VPT are distinct risk factors of abnormal plantar pressure. [ABSTRACT FROM AUTHOR]

• The high FGF21 level and NAFLD were potential risk factor for MACE, respectively. • The association between FGF21 and MACE may be interacted by NAFLD. • Early screening and intervention for NAFLD are of great importance. 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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The relationship between glycemic variability (GV) and diabetic complications has gained much interest and remains under debate. Furthermore, the association of GV with diabetic complications has not been examined in latent autoimmune diabetes of the adult (LADA). Therefore, we evaluated the relationships among several metrics of GV with diabetic retinopathy (DR) in patients with LADA and type 2 diabetes mellitus. Materials and Methods: A total of 192 patients with LADA and 2,927 patients with type 2 diabetes mellitus were enrolled. After continuous glucose monitoring for 72 h, three metrics of GV including standard deviation, coefficient of variation and mean amplitude of glycemic excursions were calculated. DR was assessed by fundus photography performed with a digital non‐mydriatic camera. Results: The prevalence of DR was 20.3 and 26.4% in LADA and type 2 diabetes mellitus patients (P < 0.001), respectively. Generally, LADA patients had fewer cardiometabolic risk factors than type 2 diabetes mellitus patients, and all GV metrics were significantly higher in LADA than in type 2 diabetes mellitus. In the multivariate logistic regression analysis, no metrics for GV were identified as independent risk factors of DR (standard deviation: P = 0.175; coefficient of variation: P = 0.769; mean amplitude of glycemic excursions: P = 0.388) in LADA. However, the standard deviation was significantly associated with DR (OR 1.15, P = 0.017) in patients with type 2 diabetes mellitus after adjusting for confounders. The independent relationships of coefficient of variation and mean amplitude of glycemic excursions with DR (P = 0.194 and P = 0.251, respectively) did not reach statistical significance in type 2 diabetes mellitus. Conclusions: GV is more strongly associated with DR in type 2 diabetes than in LADA, suggesting that different glucose‐lowering strategies should be used for these two types of diabetes. [ABSTRACT FROM AUTHOR]

Objective: Continuous glucose monitoring (CGM) has provided new measures of glycemic control that link to diabetes complications. This study investigated the association between the time in range (TIR) assessed by CGM and diabetic retinopathy (DR).Research Design and Methods: A total of 3,262 patients with type 2 diabetes were recruited. TIR was defined as the percentage of time spent within the glucose range of 3.9-10.0 mmol/L during a 24-h period. Measures of glycemic variability (GV) were assessed as well. DR was determined by using fundus photography and graded as 1) non-DR; 2) mild nonproliferative DR (NPDR); 3) moderate NPDR; or 4) vision-threatening DR (VTDR).Results: The overall prevalence of DR was 23.9% (mild NPDR 10.9%, moderate NPDR 6.1%, VTDR 6.9%). Patients with more advanced DR had significantly less TIR and higher measures of GV (all P for trend <0.01). The prevalence of DR on the basis of severity decreased with ascending TIR quartiles (all P for trend <0.001), and the severity of DR was inversely correlated with TIR quartiles (r = -0.147; P < 0.001). Multinomial logistic regression revealed significant associations between TIR and all stages of DR (mild NPDR, P = 0.018; moderate NPDR, P = 0.014; VTDR, P = 0.019) after controlling for age, sex, BMI, diabetes duration, blood pressure, lipid profile, and HbA1c. Further adjustment of GV metrics partially attenuated these associations, although the link between TIR and the presence of any DR remained significant.Conclusions: TIR assessed by CGM is associated with DR in type 2 diabetes. [ABSTRACT FROM AUTHOR]

In previous epidemiological screening in China, glycated albumin (GA) was mostly detected during the fasting state. This strict restriction causes some problems with diabetes screening. It is unclear if GA could help improve the efficiency of screening for diabetes for subjects who are not in the fasting state. The present study analyzed the differences between fasting and postload (30, 60, 120, and 180 min) GA levels. A total of 691 participants were enrolled in the present study. The Bland-Altman difference plots revealed that 95.4, 94.8, 93.6, and 93.9% of data points were within the limits of agreement for each time point. The receiver operating characteristic curve showed that the areas under the curve (AUC) for baseline GA and postload GA for every time point were 0.822 (95% CI 0.791–0.849), 0.821 (95% CI 0.790–0.848), 0.833 (95% CI 0.803–0.860), 0.840 (95% CI 0.811–0.867), and 0.840 (95% CI 0.810–0.867), with sensitivities of 67.5, 68.1, 69.3, 71.6, and 69.3%, respectively. There was no difference between the baseline and postload GA levels in either AUC or sensitivity (all p>0.05). In conclusion, postload serum GA levels were in good agreement with those at baseline, and thus, it may be reasonable to employ nonfasting measurements of GA levels for diabetes screening. [ABSTRACT FROM AUTHOR]

Serum uric acid (SUA) levels are highly heritable and an increased SUA level is one of important risk factors for gout, diabetes, metabolic syndrome, and cardiovascular diseases. The genetic variants underlying SUA remains largely unexplored. The aim was to explore new genetic variants underlying SUA in Chinese Han. We performed a genome-wide association study of SUA levels in Han Chinese. The discovery set contained 1634 samples and subsequent replication was comprised of 1649 females and 1169 males. 2620 subjects were recruited in the detailed analysis of rs671, alcohol drinking and SUA. We found a genome-wide significant association between SUA level and the SNP rs671 at ALDH2 ( P  = 1.2 × 10 −10 ) in the merged data. In addition, we also replicated the signal from rs3733590 at SLC2A9 ( P  = 1.0 × 10 −10 ). In males, about 0.21% to 1.95% of the total variance for SUA can be explained by rs671 using linear regression models in four independent cohorts. Of those, 56.75% to 93.51% might be explained by altering alcohol consumption due to rs671. No statistical association of rs671 and SUA was observed in females ( P  = 0.409). Furthermore, we observed a causal relationship between alcohol consumption and SUA in males using rs671 as an instrumental variable ( P  = 5.1 × 10 −4 ). We replicated the previous findings in SLC2A9 . Our evidence supported that rs671 was associated with SUA by affecting alcohol consumption in males. This finding strongly suggests a role for alcohol consumption in the development of hyperuricaemia and uric acid related traits. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: The present study aimed to investigate the performance of a new real‐time continuous glucose monitoring system. Materials and Methods: Interstitial glucose levels were monitored for 7 days in 63 patients with type 1 or type 2 diabetes using the Medtrum A6 TouchCare® CGM System. Venous blood was collected on a randomized day of the wear period. Plasma glucose levels were measured as reference values. Results: Among 1,678 paired sensor–reference values, 90.5% (95% confidence interval 89.1–91.9%) were within ±20%/20 mg/dL of the reference values, with a mean absolute relative difference of 9.1 ± 8.7% (95% CI: 8.9–9.2%). The percentages of paired sensor–reference values falling within zone A and B of the Clarke error grid analysis (EGA) and the type 1 diabetes consensus EGA were 99.1 and 99.8%. Continuous EGA showed that the percentages of accurate readings, benign errors, and erroneous readings were 89.9, 6.3 and 3.8%, respectively. Surveillance EGA showed that 90.6, 9.2, and 0.2% of sensor–reference values with no, slight and lower moderate risk, respectively. The mean absolute relative difference was 16.6, and 96.0% of the sensor values fell within zones A and B of the consensus EGA for hypoglycemia. More than 85% of sensor values were within ±20%/20 mg/dL of reference values, the mean absolute relative difference was <11, and >99.5% of the sensor values fell in zones A and B of the consensus EGA. Conclusions: The Medtrum real‐time continuous glucose monitoring system was numerically and clinically accurate over a large glucose range across 7 days of wear. [ABSTRACT FROM AUTHOR]

Background. Our previous study indicated that serum 1,5-anhydroglucitol (1,5-AG) levels slightly increased after a glucose load; therefore, this study was conducted to explore short-term changes in 1,5-AG levels after a steamed bread meal test (SBMT) and compare the agreement of 1,5-AG, glycated albumin (GA), and glycated hemoglobin A1c (HbA1c) levels between fasting and postprandial states after an SBMT. Methods. 104 participants were recruited and underwent a 100 g SBMT. Fasting, 30 min, and 120 min of 1,5-AG, GA, and HbA1c were measured. Results. Levels of 1,5-AG slightly increased from 30 to 120 min after an SBMT (P<0.01), and HbA1c and GA levels showed stability at 30 and 120 min. The Passing-Bablok regression linear equation showed that postprandial 1,5-AG, GA, and HbA1c levels were well fitted (all P>0.05), and Bland-Altman difference plot showed that 100% of data points for HbA1c30 and HbA1c120 fell within the limits of agreement; 94.2%, 96.2%, 95.2%, and 95.2% of data points for 1,5-AG30, 1,5-AG120, GA30, and GA120 fell within the limits of agreement, respectively. Conclusion. Agreement analyses indicated good stability of 1,5-AG, GA, and HbA1c levels after the SBMT. HbA1c had an optimal stability, which was superior to that of GA or 1,5-AG. [ABSTRACT FROM AUTHOR]

Aim: The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Methods: Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. Results: A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2.596-35.825), P = 0.009, respectively]. Conclusions: Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP. [ABSTRACT FROM AUTHOR]

Aims/Introduction It has not been reported whether chronic hepatitis B virus infection ( CHB) is associated with a specific type of diabetes. We sought to investigate the prevalence of CHB status in different diabetes subtypes among a Chinese population. Materials and Methods This was a cross-sectional study. A total of 381 patients with adult-onset autoimmune diabetes, 1,365 patients with type 2 diabetes and 1,365 non-diabetic controls were recruited from June 2005 to February 2014. The exclusion criteria included: (i) hepatitis C virus antibody positive; (ii) hepatic cirrhosis; and (iii) malignant neoplasm and severe renal dysfunction (serum creatinine >450 μmol/L). Patients were grouped as hepatitis B virus-negative and CHB status. Results Patients with type 2 diabetes had a higher prevalence of CHB than the controls in the overall population (13.5 vs 10.0%, P = 0.004) and among patients with normal hepatic function (13.3 vs 8.8%, P = 0.002). There was no difference in the prevalence of CHB status between patients with adult-onset autoimmune diabetes and the controls. Multiple logistic regression analysis showed that the odds ratio of CHB increased by ~1.5-fold in patients with type 2 diabetes than in the control group after adjustment for age, sex and body mass index, regardless of hepatic function status. Conclusions CHB status was more prevalent in patients with type 2 diabetes than in individuals with adult-onset autoimmune diabetes and the controls among the Chinese population. Further research is required to ascertain whether CHB status increases the risk of developing type 2 diabetes, or whether type 2 diabetes, but not adult-onset autoimmune diabetes, increases the risk of CHB. [ABSTRACT FROM AUTHOR]

Aims/Introduction Individuals with type 2 diabetes mellitus are vulnerable to micro- and macrovascular complications in the presence of microalbuminuria. Adipocyte fatty acid-binding protein (A-FABP) was proposed as an indicator for albuminuria in patients with diabetes. The present study aimed to explore the associations between serum A-FABP levels and microalbuminuria in the hyperglycemic population. Materials and Methods Serum A-FABP levels were detected using sandwich enzyme-linked immunosorbent assay. Microalbuminuria was identified by urinary albumin-to-creatinine ratio (UACR), when the value was between 30-300 mg/g. The participants were divided into the subgroups based on sex and the status of impaired glucose regulation or newly diagnosed type 2 diabetes mellitus. Results A total of 939 participants, consisting of 436 men and 503 women, were enrolled. Serum levels of A-FABP were much higher in participants with microalbuminuria than those without microalbuminuria. This result held true for all subgroups (all P < 0.05). For Spearman's correlation analyses, serum A-FABP levels showed a positive relationship with the UACR in men and women (both P < 0.01). Multiple stepwise regression analysis showed that serum A-FABP levels were independently and positively correlated with UACR in both sexes (men: standardized β = 0.256, P < 0.001; women: standardized β = 0.155, P = 0.001). This relationship remained significant in every subgroup (all P < 0.01). Conclusions For hyperglycemic individuals, serum A-FABP levels increased in the presence of microalbuminuria. Serum A-FABP levels were identified as an independent factor positively associated with the UACR. [ABSTRACT FROM AUTHOR]

Recently, 5 amino acids were identified and verified as important metabolites highly associated with type 2 diabetes (T2D) development. This report aims to assess the association of tryptophan with the development of T2D and to evaluate its performance with existing amino acid markers. A total of 213 participants selected from a ten-year longitudinal Shanghai Diabetes Study (SHDS) were examined in two ways: 1) 51 subjects who developed diabetes and 162 individuals who remained metabolically healthy in 10 years; 2) the same 51 future diabetes and 23 strictly matched ones selected from the 162 healthy individuals. Baseline fasting serum tryptophan concentrations were quantitatively measured using ultra-performance liquid chromatography triple quadruple mass spectrometry. First, serum tryptophan level was found significantly higher in future T2D and was positively and independently associated with diabetes onset risk. Patients with higher tryptophan level tended to present higher degree of insulin resistance and secretion, triglyceride and blood pressure. Second, the prediction potential of tryptophan is non-inferior to the 5 existing amino acids. The predictive performance of the combined score improved after taking tryptophan into account. Our findings unveiled the potential of tryptophan as a new marker associated with diabetes risk in Chinese populations. The addition of tryptophan provided complementary value to the existing amino acid predictors. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor 21 (FGF21) exerts wide-range effects on carbohydrate and lipid metabolism. However, its perturbation in type 2 diabetes mellitus (T2DM) remains elusive. Besides, previous human studies in T2DM simply investigated fasting or stimulated levels of FGF21. The current study sought to evaluate the temporal changes of circulating FGF21 in subjects with and without T2DM. Methods: Ten patients with T2DM and 16 normal controls (NC) were recruited. Participants were categorized as obese (BMI≥25 kg/m2) or lean (BMI<25 kg/m2). Blood samples were drawn every 30 min within 7 hours (8 a.m.-3 p.m.). Serum FGF21, blood glucose, insulin, free fatty acids (FFAs) and adiponectin were measured in all subjects. Results: The peak levels of FGF21 were observed in the fasting state (8 a.m.) both in T2DM and NC groups (267.35 ±158.72 ng/L vs. 178.93±121.37 ng/L, P = 0.096). FGF21 AUC did not differ significantly between the two groups (T2DM: 949.4±471.47 ng/L; NC: 883.13±561.40 ng/L, P = 0.770). Obese subjects had higher FGF21 levels than lean ones in patients either with or without T2DM. The pattern of FFAs closely resembled that of FGF21. Correlation analysis showed that temporal levels of FGF21 were significantly related to FFAs (r = 0.749, P = 0.002),but not blood glucose, insulin or adiponectin (all P> 0.05). Conclusions: These findings suggest that the pattern of circulating FGF21 does not differ significantly between T2DM and NC,although T2DM patients showed a trend toward higher fasting FGF21 than healthy subjects. The pattern of circulating FFAs is significantly associated with that of FGF21. [ABSTRACT FROM AUTHOR]

Background: Association between hyperuricaemia and chronic kidney disease has been studied widely, but the influence of uric acid on the kidneys remains controversial. We aimed to summarize the association between uric acid and diabetic kidney disease (DKD), and to evaluate the role of uric acid in DKD. Methods: We enrolled 3,212 type 2 diabetic patients in a cross-sectional study. The patients’ basic characteristics (sex, age, BMI, duration of disease, and blood pressure) and chemical parameters (triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), microalbuminuria, creatinine, and uric acid) were recorded, and the association between uric acid and DKD was evaluated. Results: In the 3,212 diabetic patients, the prevalence of diabetic kidney disease was higher in hyperuricaemic patients than in patients with normouricaemia (68.3% vs 41.5%). The prevalence of DKD increased with increasing uric acid (p <0.0001). Logistic analysis identified uric acid as an independent predictor of DKD (p <0.0001; adjusted OR (95%CI) = 1.005 (1.004–1.007), p <0.0001). Uric acid was positively correlated with albuminuria and creatinine levels (p<0.0001) but negatively correlated with eGFR (p<0.0001) after adjusting for confounding factors. Conclusions: Hyperuricaemia is a risk factor for DKD. Serum uric acid levels within the high-normal range are independently associated with DKD. [ABSTRACT FROM AUTHOR]

The overproduction of mitochondrial reactive oxygen species (ROS) plays a key role in the pathogenesis of diabetic nephropathy (DN). However, the underlying molecular mechanism remains unclear. Our aim was to investigate the role of PGC-1α in the pathogenesis of DN. Rat glomerular mesangial cells (RMCs) were incubated in normal or high glucose medium with or without the PGC-1α-overexpressing plasmid (pcDNA3-PGC-1α) for 48 h. In the diabetic rats, decreased PGC-1α expression was associated with increased mitochondrial ROS generation in the renal cortex, increased proteinuria, glomerular hypertrophy, and higher glomerular 8-OHdG (a biomarker for oxidative stress). In vitro, hyperglycemia induced the downregulation of PGC-1α, which led to increased DRP1 expression, increased mitochondrial fragmentation and damaged network structure. This was associated with an increase in ROS generation and mesangial cell hypertrophy. These pathological changes were reversed in vitro by the transfection of pcDNA3-PGC-1α. These data suggest that PGC-1α may protect DN via the inhibition of DRP1-mediated mitochondrial dynamic remodeling and ROS production. These findings may assist the development of novel therapeutic strategies for patients with DN. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the relationship between serum vitamin D level and carotid intima-media thickness (C-IMT) in Chinese postmenopausal women. Methods: Nine hundred and twenty six Chinese postmenopausal women without carotid artery plaque or history of cardiovascular disease were selected for analysis. Measurements of serum 25 hydroxyvitamin D3 (25(OH)D3) concentration and C-IMT were made by electrochemiluminescence immunoassay and B-mode ultrasound, respectively. Trend analysis was conducted according to tertiles of C-IMT. Results: The median serum 25(OH)D3 level was 11.03 ng/mL, with an interquartile range of 8.22–14.70. A decreasing trend of serum 25(OH)D3 level was accompanied by increased C-IMT tertiles (P for trend = 0.001). Correlation analysis found an inverse relationship between serum 25(OH)D3 level and C-IMT (r = –0.113, P = 0.001). After adjustment for confounding factors, multiple regression analysis showed that serum 25(OH)D3 level independently and negatively associated with C-IMT (Standard β = –0.112, P < 0.001). Moreover, the inverse correlation of serum 25(OH)D3 with C-IMT was also found in a subgroup of women with normal glucose tolerance, blood pressure and body mass index, and without undergoing lipid-lowering therapy (standard β = –0.140, P = 0.018). Conclusions: Serum 25(OH)D3 level was inversely correlated with C-IMT in Chinese postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion. Method: We recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined. Results: SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively). Conclusions: Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population. [ABSTRACT FROM AUTHOR]