Search

As a sensor, glucokinase (GK) controls glucose homeostasis, which progressively declines in patients with diabetes. GK maintains the equilibrium of glucose levels and regulates the homeostatic system set points. Endocrine and hepatic cells can both respond to glucose cooperatively when GK is activated. GK has been under study as a therapeutic target for decades due to the possibility that cellular GK expression and function can be recovered, hence restoring glucose homeostasis in patients with type 2 diabetes. Five therapeutic compounds targeting GK are being investigated globally at the moment. They all have distinctive molecular structures and have been clinically shown to have strong antihyperglycemia effects. The mechanics, classification, and clinical development of GK activators are illustrated in this review. With the recent approval and marketing of the first GK activator (GKA), dorzagliatin, GKA's critical role in treating glucose homeostasis disorder and its long‐term benefits in diabetes will eventually become clear. [ABSTRACT FROM AUTHOR]

• The thermal and mechanical performance of the sCO2 solar cavity receiver were researched. • Large-diameter coiled tubes harm the receiver's thermal efficiency and safety. • Curvature of the coiled tube has the opposite effect on the thermal efficiency and safety of the receiver. • Cloud cover has a large influence on the temperature and stress of the solar receiver. • Solar receiver start-up early, the large flow rate produces low thermal stress. Solar thermal power systems rely on high-temperature cavity receivers. Guaranteeing the effective and secure operation of a receiver involves researching the impacts of various geometric parameters and operating conditions on its thermal performance and mechanical qualities. To examine the impacts of diameter, curvature, and various operating conditions on the thermal and mechanical performance of a receiver, a coupled thermal–mechanical model was created and assessed. The findings showed that the spiral coiled tube's thermal stress distribution is very nonuniform. Thermal efficiency declines and maximum stress rises from 74.9 MPa to 171.87 MPa as the diameter increases from 10 mm to 30 mm. The thermal efficiency rises when the curvature goes from 1/190 to 1/130, but the stress rises as well. The outlet temperature drops by 73.46 K after 5 min of cloud cover; cloud cover and startup conditions will result in rapid variations in stress and temperature on the coiled tube wall, endangering the receiver's safe function and shortening its lifespan. [ABSTRACT FROM AUTHOR]

To evaluate the role of insulin resistance and beta cell function to increasing fasting plasma glucose (FPG), 1,272 Chinese subjects (18-80 years of age) were divided into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined glucose intolerance (CGI), and type 2 diabetes mellitus (T2DM) according to oral glucose tolerance test. Insulin sensitivity was measured by Matsuda index (ISI) and homeostasis model assessment of insulin resistance (1/HOMA-IR); β-cell function adjusted by insulin sensitivity was assessed from disposition index (DI) at basal DI (homeostasis model assessment of β-cell function (HOMA-B) × [1/HOMA-IR]), early-phase DI (the ratio of total insulin AUC and total glucose AUC during 0-30 min of the OGTT (InsAUC/GluAUC) × ISI) and total DI (the ratio of total insulin AUC and total glucose AUC during 0-120 min of the OGTT (InsAUC/GluAUC) × ISI). Compared with NGT, in IFG, ISI (−23%), DI (−38%), DI (−30%), and DI (−31%) were decreased significantly. As the FPG increased across categories classified by FPG levels from NGT → IFG → T2DM with 2 h PG < 7.8 mmol/l, ISI, DI, DI and DI showed decline beginning from normal range of FPG, compared with the reference category of FPG < 4.0 mmol/l. Correlation analysis showed that ISI and DI were correlated inversely with FPG concentration ( r = −0.242 for ISI, r = −0.933 for DI, r = −0.806 for DI, r = −0.817 for DI; P < 0.001). Both the impairment of beta cell function and insulin sensitivity started at the low point of FPG within the normoglycemic range and contributed to the deterioration of fasting glucose. [ABSTRACT FROM AUTHOR]

The article presents the guidelines on stem cell therapy for diabetes from the Chinese Diabetes Society (CDS). It encompass the stem cell therapy for the treatment of diabetes through pancreatic transplantation and Islet transplantation. It details the position statement of CDS in areas such as development of novel treatments, therapy at preclinical stage, and current issues on stem cell-based treatment for diabetes.

Abstract: Background: Hyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese. Methods: We conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls. Results: Compared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR=0.49, 95% CI 0.32–0.77, P <0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤50) (adjusted OR=0.35, 95% CI 0.20–0.61, P <0.0001), and similar results were observed in males (adjusted OR=0.37, 95% CI 0.21–0.66, P =0.001) and urban participants (adjusted OR=0.35, 95% CI 0.21–0.58, P <0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio. Conclusions: Our present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the study were to determine the following: the status of glycemic control in patients with type 2 diabetes mellitus (DM) at primary, secondary, and tertiary hospitals in the Jiangsu province of China; and the factors associated with achieving glyce-mic targets. Methods: This study, in which patients were enrolled from July 20 to 31, 2009, at 56 diabetes centers, used a multiple-stage, stratified sampling method to select a representative sample of the population with DM in Jiangsu. The sampling process was stratified by geographic and demographic regions, and by the outpatient numbers in the hospitals. A primary hospital was defined as a community medical institution that provided primary health services; a secondary hospital was a local medical institution that provided comprehensive health services; and a tertiary hospital was a regional medical institution that provided comprehensive and specialist health services. In primary hospitals, patients with DM were treated by general physicians; at secondary and tertiary hospitals, they were seen by specialists. Also, primary and tertiary hospitals treated patients in cities, whereas secondary hospitals treated patients from towns or rural areas. Patients with a medical history of type 2 DM for >6 months and registration at each diabetes center for ≥6 months, and who were residents of Jiangsu province, were recruited. During the patient enrollment visit, information about DM complications and comor-bidities, as well as DM management, was obtained by retrospectively reviewing medical records; basic patient data (eg, date of birth, sex, weight, height) were obtained by patient interview. Blood samples were collected for assessment of glycosylated hemoglobin (HbA1c) at a central laboratory. Results: Of 3046 sampled subjects, the analysis was performed in 2966 subjects with complete data. The mean (SD) HbA1c value for analyzed patients was 7.2% (1.6%). The proportion of patients with tight glycemic control was 40.2% (1193/2966) when a threshold of HbA1c <6.5% was used, and 56.1% (1665/2966) when a threshold of HbA1c <7.0% was used. Compared with patients who had inadequate glycemic control, those with tight control were younger (P < 0.001), had shorter duration of DM (P < 0.001), had lower body mass index (BMI) (P = 0.005 for HbA1c <6.5% and P = 0.01 for HbA1c <7.0%), had more education (P < 0.001) and income (P = 0.003 for HbA1c <6.5% and P = 0.008 for HbA1c <7.0%), were more likely to monitor their glucose (P = NS for HbA1c <6.5% and P = 0.043 for HbA1c <7.0%) and attend DM education (P = 0.027 for HbA1c <6.5% and P = 0.002 for HbA1c <7.0%) at least once a month, and were more likely to receive oral antidiabetic drugs (OADs) (P < 0.001). Age, BMI, and DM duration did not differ significantly between hospital types. Compared with primary (36.2%) and secondary hospitals (36.5%), tertiary hospitals (42.2%) had more patients with HbA1c <6.5% (P = 0.043); tertiary hospitals also had more patients with once-monthly glucose self-monitoring (P = 0.001), patients with higher income (P < 0.001) and education (P < 0.001), and those who were more likely to use ≥2 OADs or insulin with OADs (P < 0.001). Conclusion: The overall status of glycemic control was unsatisfactory during the study period, although patients at tertiary hospitals appeared to have better control than those at primary or secondary hospitals. [Copyright &y& Elsevier]

Objective To explore the diagnostic value of quantitative sensory testing (QST) in diabetic peripheral neuropathy in patients with type 2 diabetes mellitus (T2DM). Methods Patients with T2DM aged 18-70 years in Nanjing Drum Tower Hospital from May 2020 to February 2021 were retrospectively analyzed. QST parameters [warm detection threshold (WDT), cold detection threshold (CDT)], heat pain threshold (HPT) and cold pain threshold (CPT) were collected, and nerve conduction velocity (NCV) parameters of both lower limbs were measured, including common peroneal nerve conduction velocity, sural nerve conduction velocity, tibial nerve conduction velocity, etc. Patients received QST and NCV for allocation into different neuropathy groups according to the diagnostic criteria: nondiabetic peripheral neuropathy (NDPN) group, small fiber neuropathy (SFN) group and mixed fiber neuropathy (MFN) group. The t-test or one-way analysis of variance (ANOVA), Mann Whitney U or Kruskal Wallis H test, or χ2 test were used to compare the general clinical data between groups. Multivariate logistic regression analysis was used to analyze the risk factors of DPN. Spearman correlation method was used to analyze the correlation between QST parameters and NCV. Receiver operating characteristic curve (ROC) analysis was used to evaluate the sensitivity, specificity and diagnostic value of QST for MFN. Results A total of 279 patients were included, including 111 in NDPN group, 116 in SFN group and 52 in MFN group. Compared with SFN group, MFN group presented lower CDT and CPT, higher WDT and HPT (all P< 0.05). The results of correlation analysis showed that the common peroneal nerve conduction velocity, sural nerve conduction velocity and tibial nerve conduction velocity of both lower limbs were positively correlated with CDT (r=0.264, 0.366 and 0.288 respectively) and CPT (r=0.226, 0.253 and 0.236 respectively) (all P<0.05), They were negatively correlated with WDT (r=-0.274, -0.338 and -0.268 respectively) and HPT (r=-0.246, -0.281 and -0.192 respectively) (all P<0.05). The results of ROC model showed that when WDT+CDT was used to diagnose MFN, the product under the curve was 0.840, the sensitivity was 86.3%, and the specificity was 71.8% (P<0.001). Conclusion QST was able to exhibit a high early diagnostic value for diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

GK acts as a 'glucose sensor' to regulate glucose homeostasis. Dorzagliatin is a novel dual-acting allosteric GKA targeting both pancreatic and liver GK. The study aimed to confirm the efficacy and safety of dorzagliatin as a monotherapy in Chinese T2D patients. It is the first successful Phase III trial for a GKA. It was a multicenter, randomized, double-blind, placebo-controlled trial. 463 drug-naïve adult subjects were randomized to 75 mg dorzagliatin or placebo (2:1) BID for 24 wks. The primary endpoint was the change in HbA1c from baseline to wk 24. Secondary endpoints included 2h PPG and other glycemic variables. Safety assessment included AE, hypoglycemia, laboratory tests, ECG, etc. The MMRM results suggested the LS mean change in HbA1c from baseline at wk 24 was -1.07% in dorzagliatin group, significantly lower than the placebo group (P<0.0001). The homeostatic control rate (HbA1c <7% without hypoglycemia), was 45.0% in dorzagliatin group compared to 21.5% in placebo group (P<0.0001). At wk 24, the mean change of 2h PPG (mM) from baseline was -3.05 and -0.78 for the dorzagliatin and placebo groups (P<0.0001). The mean change of FPG (mM) from baseline at wk 24 was -0.70 in dorzagliatin group and -0.34 in placebo group with no significant difference. The change of HbA1c from baseline at each study visit was significantly lower (P<0.001) in dorzagliatin group compared with the placebo group. Dorzagliatin was well-tolerated during the 24 wks and had a good safety profile. Fewer than 1% of patients experienced incident of hypoglycemia over 24 wks. There were no death, drug-related SAEs, and severe hypoglycemia in subjects treated with dorzagliatin. Overall, dorzagliatin had a favorable effect on glycemic control and a good safety profile over 24 wks in Chinese T2D patients. It brings the reality a step further in developing a novel T2D drug with GKA mechanism of action. Disclosure: D. Zhu: None. Y. Zhang: None. L. Chen: None. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the effectiveness of dulaglutide, a medication for type 2 diabetes, in Chinese patients. The study found that dulaglutide improved glycemic control, reduced body weight, and decreased insulin dosage compared to a placebo. The researchers also analyzed how patient characteristics influenced the medication's efficacy. The study was conducted ethically and registered with ClinicalTrials.gov. The results suggest that patients with higher baseline HbA1c levels may experience greater improvements in glycemic control, while those with higher baseline fasting serum glucose levels may experience greater weight loss. However, the study has limitations and further research is needed to fully understand these findings. [Extracted from the article]

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]

Objective To identify the candidate pathogenic loci in exons of susceptibility genes for diabetic retinopathy (DR) in Chinese Han population. Methods This was a case-control study. The patients with type 2 diabetes mellitus (T2DM) diagnosed in Drum Tower Hospital Affiliated to Nanjing University Medical School between January 2015 and September 2018 were retrospectively analyzed. There were 101 DR patients in the case group and 103 non-DR patients in the control group. General information and laboratory results of patients were collected. The exons of DR susceptibility genes TBC1D4, COMMD6, UCHL3, LRP2, BBS5, ARL4C, and SH3BP4 in Chinese population were captured and sequenced by the second-generation sequencing technology of FastTarget target region enrichment. Independent sample t test and chi-square test were used to compare the general demographic characteristics between the two groups. Association between common/rare variants and DR risk was evaluated by logistic regression and counting method. Further, for our identified novel DR-related variants, functional annotation was adopted to assess their potential biological functions. Results The age and duration of diabetes in the case group were significantly lower than those in the control group (P<0.05), while the level of glycosylated hemoglobin was significantly higher than that in the control group (P<0.05). Logistic regression analysis showed that four of 82 common variants were associated with DR (P<0.05), including LRP2 rs13417389, LRP2 rs2229267, LRP2 rs2229268, and LRP2 rs886055072. Besides, 14 DR-related rare functional variants with CADD score greater than 20 were identified: LRP2 rs764804647 G>A, LRP2 rs538396567 T>A, LRP2 Chr2: 170010984 T>A, LRP2 Chr2: 170050282 C>A, LRP2 Chr2: 170129538 T>A, LRP2 Chr2: 170129538 T>C, LRP2 Chr2: 170129539 G>A, LRP2 Chr2: 170129539 G>T, LRP2 rs754796717 G>C, LRP2 rs529409328 C>G, UCHL3 Chr13: 76135016 A>G, TBC1D4 Chr13: 75876471 C>A, TBC1D4 rs201459702 T>C, SH3BP4 Chr2: 235950303 G>A. Conclusion The 14 DR-related rare functional variants identified in this study could be used as candidate pathogenic loci for diabetic retinopathy in Chinese Han population. [ABSTRACT FROM AUTHOR]

Introduction: Insulin degludec (degludec), an ultra-long-acting basal insulin analogue, provides equivalent glycemic control to other basal insulin analogues, with lower risk of hypoglycemia and flexible dosing. Chinese TREsiba AudiT (CN-TREAT) investigated outcomes with degludec in people with type 2 diabetes (T2D) in routine clinical practice in China. Methods: This was a retrospective chart review study in adults with T2D initiating or switching to degludec at 50 sites in China between January 2020 and July 2021. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study (EOS; week 20). Secondary endpoints included change from baseline to EOS in fasting plasma glucose (FPG), self-measured plasma glucose (SMPG), daily insulin dose, and rate of hypoglycemia. Results: Data from 936 participants were included (499 insulin-naïve; 437 insulin-experienced). Mean (95% confidence interval [CI]) HbA1c change from baseline to EOS was − 1.48%-points (− 1.57; − 1.38; P < 0.0001) overall: − 1.95%-points (− 2.08; − 1.81; P < 0.0001) in insulin-naïve participants and − 0.95%-points (− 1.08; − 0.82; P < 0.0001) in insulin-experienced participants. Mean (95% CI) changes in FPG and SMPG were − 2.27 mmol/L (− 2.69; − 1.85; P < 0.0001) and − 2.89 mmol/L (− 3.52; − 2.25; P < 0.0001), respectively, with similar reductions in insulin-naïve and insulin-experienced subgroups. Rate of hypoglycemia did not change statistically significantly from baseline to EOS overall, or in insulin-experienced participants, except when adjusted for baseline hypoglycemia. Basal insulin dose did not change statistically significantly in insulin-experienced participants. Conclusion: In routine clinical practice in China, initiation or switching to degludec was associated with improvements in glycemic control in people with T2D, with no increased risk of hypoglycemia. Trial Registration: ClinialTrials.gov, NCT04227431. [ABSTRACT FROM AUTHOR]

Aim: To determine the efficacy and safety of once‐weekly dulaglutide added to basal insulin in Chinese patients with type 2 diabetes mellitus (T2DM) with inadequate glycaemic control. Materials and Methods: In the phase III, double‐blind AWARD‐CHN3 study, Chinese patients with T2DM (N = 291) and glycated haemoglobin (HbA1c) ≥7.0% and ≤11.0% receiving stable doses of basal insulin glargine with metformin and/or acarbose were randomized (1:1) to receive add‐on dulaglutide 1.5 mg once weekly or placebo once weekly. The primary endpoint was the superiority of dulaglutide/glargine to placebo/glargine for change from baseline in HbA1c at Week 28. Results: The least squares (LS) mean ± standard error change in HbA1c from baseline to Week 28 was −2.0 ± 0.08% with dulaglutide/glargine and −1.1 ± 0.07% with placebo/glargine (LS mean difference: −1.0%, 95% confidence interval [CI] –1.1 to −0.8; P < 0.001), and more patients receiving dulaglutide/glargine achieved HbA1c levels <7.0% (75.9% vs. 33.8%; P < 0.001 vs. placebo/glargine). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: −1.2 kg, 95% CI –1.8 to – 0.6; P < 0.001). Reductions in fasting serum glucose were greater with dulaglutide/glargine than with placebo/glargine (LS mean difference: −0.8 mmol/L, 95% CI –1.1 to – 0.5; P < 0.001). The incidence of hypoglycaemia was similar with dulaglutide/glargine and placebo/glargine (29.2% vs. 31.3%; P = 0.704); no patient in either group had severe hypoglycaemia. The most common treatment‐emergent adverse events with dulaglutide/glargine were decreased appetite (22.2%), diarrhoea (13.2%) and nausea (10.4%). Conclusions: Dulaglutide added to basal insulin was efficacious and well tolerated in Chinese patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: Diabetes and hypertension are major modifiable risk factors for cardiovascular disease. Previous clinical trials have demonstrated that intensive blood pressure reduction lowers the risk of cardiovascular disease and all‐cause mortality compared to standard blood pressure reduction among patients without diabetes. However, optimal levels of blood pressure control in patients with diabetes remain uncertain. Methods: The Blood Pressure Control Target in Diabetes (BPROAD) study is a multicenter, randomized controlled trial conducted in mainland China. We plan to enroll 12 702 participants aged ≥50 years with type 2 diabetes, an increased cardiovascular risk, and systolic blood pressure ≥130 mm Hg from 150 study centers. Participants are randomly assigned to intensive (a systolic target of <120 mm Hg) or standard (a systolic target of <140 mm Hg) blood pressure treatment group. Participants will be followed monthly for blood pressure management in the first 3 months and then every 3 months afterward. The primary study outcome is a composite of major cardiovascular events including nonfatal myocardial infarction, nonfatal stroke, treated or hospitalized heart failure, and cardiovascular death. Data will be collected every 3 months for up to 5 years and a blinded outcome committee will adjudicate all clinical outcomes. The BPROAD study is designed to have 90% statistical power to detect a 20% reduction in the primary study outcome at a two‐sided significance level of 0.05. Conclusions: The BPROAD study will provide important evidence as to whether intensive blood pressure management has additional benefits on cardiovascular disease and all‐cause mortality among patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Both hypertension and diabetes are risk factors of dementia. Proper management of blood pressure (BP) and blood glucose is critical in delaying cognitive decline in the elderly. However, little is known regarding the optimal BP target in type 2 diabetes (T2DM) for the management of cognitive decline. Methods: The Blood Pressure Control Target in Diabetes (BPROAD) study is a nationwide, multicenter, randomized controlled trial that will enroll 12 702 T2DM patients with elevated systolic BP and increased cardiovascular risk from approximately 150 study centers across mainland China to undergo randomly antihypertensive treatment achieving systolic BP <120 mm Hg or systolic BP <140 mm Hg for up to 5 years. All BPROAD participants will take part in the BPROAD Cognitive Study for the assessment of cognitive function at baseline and annual visits by blinded outcome assessors to determine whether intensive BP treatment reduces risk of dementia and mild cognitive impairment (MCI) compared with standard BP treatment in patients with T2DM. In addition, approximately 1000 BPROAD participants will be enrolled in the magnetic resonance imaging (MRI) substudy to receive brain MRI at baseline and at closeout. The primary outcome of BPROAD Cognitive Study is a composite of all‐cause dementia and MCI. Conclusions: The BPROAD Cognitive Study will provide crucial clinical trial data on the possible benefit of an intensive systolic BP lowering strategy in reducing dementia and MCI in patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: This retrospective multicenter study evaluated the efficacy and safety of bariatric surgery in Chinese patients with obesity. Methods: Patients with obesity who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux‐en‐Y gastric bypass and completed a 12‐month follow‐up between February 2011 and November 2019 were enrolled. Weight loss, glycemic and metabolic control, insulin resistance, cardiovascular risk, and surgery‐related complications at 12 months were analyzed. Results: We enrolled 356 patients aged 34.3 ± 0.6 years with a mean body mass index of 39.4 ± 0.4 kg/m2. Successful weight loss occurred in 54.6%, 86.8%, and 92.7% of patients at 3, 6, and 12 months, respectively, with no difference in percent excess weight loss between the laparoscopic sleeve gastrectomy and laparoscopic Roux‐en‐Y gastric bypass surgery groups. The average percentage of total weight loss was 29.5% ± 0.6% at 12 months; 99.4%, 86.8%, and 43.5% of patients achieved at least 10%, 20%, and 30% weight loss, respectively, at 12 months. Significant improvements in metabolic indices, insulin resistance, and inflammation biomarkers were observed at 12 months. Conclusions: Bariatric surgery resulted in successful weight loss and improved metabolic control, insulin resistance, and cardiovascular risk in Chinese patients with obesity. Both laparoscopic sleeve gastrectomy and laparoscopic Roux‐en‐Y gastric bypass are suitable approaches for such patients. [ABSTRACT FROM AUTHOR]

Introduction: Left ventricular global longitudinal strain (GLS) is considered to be the first marker of diabetes mellitus-related subclinical cardiac dysfunction, but whether it is attributable to fat mass and distribution remains uncertain. In this study, we explored whether fat mass, especially fat mass in the android area, is associated with subclinical systolic dysfunction before the onset of cardiac disease. Methods: We conducted a single-center prospective cross-sectional study between November 2021 and August 2022 on inpatients of the Department of Endocrinology, Nanjing Drum Tower Hospital. We included 150 patients aged 18–70 years with no signs, symptoms, or history of clinical cardiac disease. Patients were evaluated with speckle tracking echocardiography and dual energy X-ray absorptiometry. The cutoff values for subclinical systolic dysfunction were set at a global longitudinal strain (GLS) < 18%. Results: After adjusting for sex and age, patients with GLS < 18% had a higher mean (± standard deviation) fat mass index (8.06 ± 2.39 vs. 7.10 ± 2.09 kg/m2, p = 0.02), higher mean trunk fat mass (14.9 ± 4.9 vs. 12.8 ± 4.3 kg, p = 0.01), and higher android fat mass (2.57 ± 1.02 vs. 2.18 ± 0.86 kg, p = 0.02) than those in the GLS ≥ 18%. Partial correlation analysis showed that the fat mass index, truck fat mass, and android fat mass were negatively correlated with GLS after adjusting for sex and age (all p < 0.05). Adjusted for traditional cardiovascular metabolic factors, fat mass index (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.05–1.55, p = 0.02), trunk fat mass (OR 1.13, 95% CI 1.03–1.24, p = 0.01), and android fat mass (OR 1.77, 95% CI 1.16–2.82, p = 0.01) were independent risk factors for GLS < 18%. Conclusion: Among patients with type 2 diabetes mellitus without established clinical cardiac disease, fat mass, especially android fat mass, was associated with subclinical systolic dysfunction independently of age and sex. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy, phase III study, randomized trial, type 2 diabetes Keywords: diabetic retinopathy; phase III study; randomized trial; type 2 diabetes EN diabetic retinopathy phase III study randomized trial type 2 diabetes 894 898 5 02/03/23 20230301 NES 230301 BACKGROUND/CONTEXT Diabetic retinopathy (DR) and chronic kidney disease (CKD) are two major forms of microvascular complications in patients with type 1 diabetes and type 2 diabetes (T2D), with shared risk factors (such as poor glycaemic control, smoking, hypertension and dyslipidaemia) and clinical manifestations (microvascular lesions).[1] The steroid hormone aldosterone, which binds to mineralocorticoid receptors, promotes vascular pathology in the retina relevant to the development of DR[2]; antagonism of the retinal mineralocorticoid receptor-aldosterone system may delay progression.[3] Finerenone, a potent and selective, orally administered, non-steroidal mineralocorticoid receptor antagonist (MRA), slowed progression of CKD and reduced the risk of cardiovascular outcomes versus placebo in patients with CKD and T2D in the FIDELIO-DKD (NCT02540993; n = 5674) and FIGARO-DKD (NCT02545049; n = 7352) randomized phase 3 trials.[[4]] In total, 2657 (46.8%) patients in FIDELIO-DKD and 2265 (30.8%) in FIGARO-DKD had DR at baseline.[[6]] No further details on DR were collected in these studies. Effect of finerenone on the occurrence of vision-threatening complications in patients with non-proliferative diabetic retinopathy: Pooled analysis of two studies using routine ophthalmological examinations from clinical trial participants (ReFineDR/DeFineDR) Diabetic retinopathy is a prognostic factor for progression of chronic kidney disease in the patients with type 2 diabetes mellitus. [Extracted from the article]

Aims/Introduction: To explore whether carotid atherosclerosis is an independent risk factor for small fiber nerve dysfunction in type 2 diabetes mellitus patients. Materials and Methods: A total of 247 type 2 diabetes patients from Nanjing Drum Tower Hospital received carotid ultrasonography and quantitative sensory testing, including cold and warm detection thresholds, and some patients received cold and heat pain detection thresholds, respectively. According to the results of quantitative sensory testing, patients were divided into normal small fiber nerve function (NSF) and small fiber nerve dysfunction (SFD) group. Meanwhile, patients were divided into the non‐carotid atherosclerosis group, carotid intimal thickening, unilateral carotid atherosclerosis and bilateral carotid atherosclerosis group. The correlation between carotid ultrasonography with quantitative sensory testing parameters was analyzed by SPSS 26.0. Results: First, the incidence rate of SFD increased significantly in patients with carotid atherosclerosis (72.2%, P < 0.001) especially in bilateral carotid atherosclerosis (81.7%, P < 0.001). Second, compared with the NS group, the carotid intima‐media thickness in SFD was thicker (P = 0.018) and the size of atherosclerotic plaque was larger (P < 0.001). In addition, the cold detection threshold decreased (P < 0.001), whereas the warm detection threshold (P < 0.001) and heat pain detection threshold (P < 0.001) increased as aggravation of carotid atherosclerosis. In the correlation analysis, the size of atherosclerotic plaque presented a positive correlation with the warm detection threshold (r = 0.476, P < 0.001) and heat pain detection threshold (r = 0.213, P < 0.001), but presented a negative correlation with the cold detection threshold (r = −0.239, P < 0.01). Furthermore, carotid atherosclerosis (odds ratio 2.326, P = 0.017), especially bilateral carotid atherosclerosis (odds ratio 5.042, P = 0.001), was an independent risk factor for SFD (P < 0.05). Conclusions: Carotid atherosclerosis was significantly associated with quantitative sensory testing and found to be an independent risk factor for small fiber nerve dysfunction in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Liver dysfunction is a common complication of Graves’ disease (GD) that may be caused by excessive thyroid hormone (TH) or anti-thyroid drugs (ATDs). Radioactive iodine (RAI) therapy is one of the first-line treatments for GD, but it is unclear whether it is safe and effective in patients with liver dysfunction. 510 consecutive patients with GD receiving first RAI were enrolled in the study, and followed up at 3-, 6- and 12-month. Liver dysfunction was recorded in 222 (43.5%) patients. GD patients with liver dysfunction had higher serum levels of free triiodothyronine (FT3) (median 27.6 vs. 20.6 pmol/L, p < 0.001) and free thyroxine (FT4) (median 65.4 vs. 53.5 pmol/L, p < 0.001) levels than those with normal liver function. Binary logistic regression analysis showed that duration of disease (OR = 0.951, 95% CI: 0.992–0.980, p = 0.001) and male gender (OR = 1.106, 95% CI: 1.116–2.384; p = 0.011) were significant differential factors for liver dysfunction. Serum TSH levels were higher in patients with liver dysfunction at all 3 follow-up time points (p = 0.014, 0.008, and 0.025 respectively). FT3 level was lower in patients with liver dysfunction at 3-month follow-up (p = 0.047), but the difference disappeared at 6 and 12 months (p = 0.351 and 0.264 respectively). The rate of euthyroidism or hypothyroidism was higher in patients with liver dysfunction than in those with normal liver function at 3 months (74.5% vs 62.5%; p = 0.005) and 6 months (82.1% vs 69.1%; p = 0.002) after RAI treatment, but the difference did not persist at 12-month follow-up (89.6% vs 83.2%, p = 0.081).There were no statistically significant differences in treatment efficacy (94.48% vs 90.31%, p = 0.142), incidence of early-onset hypothyroidism (87.73% vs 83.67%, p = 0.277), and recurrence rate (4.91% vs 7.14%, p = 0.379) between the 2 groups at 12-month follow-up. In conclusion, the efficacy of RAI was comparable in GD patients with liver dysfunction and those with normal liver function. [ABSTRACT FROM AUTHOR]

Background: The therapeutic potential of mesenchymal stem cells (MSCs) in type 1 diabetes (T1D) has been demonstrated in both preclinical and clinical studies. MSCs that have been used in research on T1D are derived from various tissue sources, with bone marrow (BM) and umbilical cord (UC) tissues being the most commonly used. However, the influence of tissue origin on the functional properties and therapeutic effects of MSCs in T1D remains unclear. This study aimed to compare the therapeutic efficacy of UC-MSCs and BM-MSCs in a mouse model of T1D as well as in patients with T1D. Methods: In non-obese diabetic (NOD) mice, the development of diabetes was accelerated by streptozotocin injections. Thereafter, diabetic mice were randomized and treated intravenously with UC-MSCs, BM-MSCs or phosphate-buffered saline as a control. Blood glucose and serum insulin were measured longitudinally after transplantation. At 14 days post-transplantation, pancreatic tissues were collected to assess insulitis and the β-cell mass. Flow cytometry was performed to evaluate the composition of T lymphocytes in the spleen and pancreatic lymph nodes of the NOD mice. In our retrospective study of patients with T1D, 28 recipients who received insulin therapy alone or a single transplantation of UC-MSCs or BM-MSCs were enrolled. The glycaemic control and β-cell function of the patients during the first year of follow-up were compared. Results: In NOD mice, UC-MSC and BM-MSC transplantation showed similar effects on decreasing blood glucose levels and preserving β cells. The regulation of islet autoimmunity was examined, and no significant difference between UC-MSCs and BM-MSCs was observed in the attenuation of insulitis, the decrease in T helper 17 cells or the increase in regulatory T cells. In patients with T1D, MSC transplantation markedly lowered haemoglobin A1c (HbA1c) levels and reduced insulin doses compared to conventional insulin therapy. However, the therapeutic effects were comparable between UC-MSCs and BM-MSCs, and they also exerted similar effects on the endogenous β-cell function in the patients. Conclusion: In conclusion, both UC-MSCs and BM-MSCs exhibited comparable therapeutic effects on improving glycaemic control and preserving β-cell function in T1D. Considering their abundance and higher cell yields, UC-MSCs appear to be more promising than BM-MSCs in clinical applications. Trial registration NCT02763423. Registered on May 5, 2016—Retrospectively registered, https://www.clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

Purpose We compared the efficacy and safety of beinaglutide, a glucagon-like peptide-1 (GLP-1) analogue with metformin in lowering the bodyweight of patients who were overweight/obese and non-diabetic. Patients and Methods Seventy-eight non-diabetic patients were randomly selected and beinaglutide or metformin was administered for 12 weeks. The primary endpoints were changes in body weight and the proportions of patients who lost≥5 and≥10% of their baseline body weights. Results A total of 64 patients completed the study; patients in the beinaglutide group exhibited more bodyweight loss than those in the metformin group [(9.5±0.8%; 9.1±0.9 kg) and (5.1±0.9%; 4.5±0.8 kg), respectively, corresponding to a difference of approximately 4.5 kg (95% confidence interval, 2.2–6.9 kg; P <0.01)]. In the beinaglutide group, 90.6 and 40.6% of the patients lost≥5 and≥10% of their body weight, respectively, whereas, in the metformin group, these rates were 46.9 and 12.5%, respectively (P <0.01 and P< 0.05). Weight loss following beinaglutide treatment mainly resulted from the loss of fat mass. Compared to metformin, beinaglutide induced a greater decrease in the body mass index, weight circumference, percent body fat, and body fat mass (total, trunk, limb, android, and gynoid). Additionally, beinaglutide decreased serum insulin levels and ameliorated insulin resistance. Conclusions Beinaglutide is more efficient than metformin at reducing weight and fat mass in patients who are overweight/obese and non-diabetic. Beinaglutide may be a useful therapeutic option for overweight/obesity control in the Chinese population. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the immunogenicity of LY2963016 insulin glargine (LY IGlar) versus originator insulin glargine (IGlar [Lantus®]) in Chinese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). Materials and Methods: ABES and ABET were prospective, randomized, active control, open‐label, phase III studies, which enrolled Chinese patients with T1DM (N = 272) and T2DM (N = 536), respectively. Using data from these trials, immunogenicity of LY IGlar and IGlar was evaluated by comparing the proportion of patients with detectable anti‐insulin glargine antibodies and the median antibody levels (percent binding) between the treatment groups. The incidence of anti‐insulin antibodies and treatment‐emergent antibody response (TEAR) were compared using Fisher's exact test or Pearson's chi‐squared test. Levels of anti‐insulin antibodies were compared using the Wilcoxon rank‐sum test. We also evaluated the relationship between antibody formation or TEAR and clinical outcomes using analysis of covariance, negative binomial regression, or partial correlations. Results: There were no significant treatment differences in the incidence of detectable anti‐insulin antibodies, median antibody levels or TEAR, overall or at Week 24 with last observation carried forward, and median antibody levels were low (<5%) after 24 weeks of treatment, in patients with T1DM or T2DM. Levels of anti‐insulin antibodies and development of TEAR were not associated with efficacy (glycated haemoglobin, insulin dose [U/kg/d] and hypoglycaemia) or safety outcomes. Conclusions: The immunogenicity profiles of LY IGlar and IGlar are similar, with low levels of anti‐insulin antibodies observed for both insulins. No association was observed between antibody levels or TEAR status and clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the alteration of circulating CD34+KDR+CD133+ endothelial progenitor cells (EPCs) in patients with newly diagnosed type 2 diabetes and the mechanism of the effect of early intensive insulin therapy. Methods: In this study, 36 patients with newly diagnosed type 2 diabetes and 22 control subjects matched by age and gender were enrolled. All of the patients with diabetes received intensive insulin therapy. The number of EPCs was assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor (KDR). Results: Levels of circulating CD34+KDR+CD133+ EPCs were higher in patients with diabetes compared to control subjects and significantly decreased after intensive insulin therapy. Levels of vascular endothelial growth factor (VEGF), a major contributor to EPC mobilization, were significantly higher in patients with diabetes compared to control subjects, and dramatically decreased after insulin therapy. Importantly, VEGF levels correlated with number of EPCs. Moreover, compared with control subjects, pro-inflammatory cytokines and oxidative stress were significantly higher in patients with diabetes and markedly decreased after intensive insulin therapy. Conclusions: These results showed that type 2 diabetes is associated with an increase of circulating CD34+KDR+CD133+ EPCs at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserving effect on EPC level partly through improving inflammation status and oxidative stress, thereby implying a putative long-term beneficial effect on vascular integrity via suspending excessive EPC exhaustion. Clinical Trial Number: NCT03710811. [ABSTRACT FROM AUTHOR]

Highlights: [•] Facile patterning approach for PEDOT:PSS was introduced. [•] With silver interlayer, traditional photolithography could be used. [•] No obvious influence towards PEDOT:PSS was observed after patterning. [•] This method can be applied to flexible and large-area substrates. [•] High resolution pixel OLEDs were achieved. [ABSTRACT FROM AUTHOR]

Background: Although type 1 diabetes (T1D) is typically described as a T cell-mediated autoimmune disease, increasing evidence for a role of B cells has emerged. However, the pivotal disease-relevant B cell subset and its contribution to islet autoimmunity remain elusive. Methods: The frequencies and phenotypic characteristics of circulating B cell subsets were analyzed using flow cytometry in individuals with new-onset T1D, long-term T1D, type 2 diabetes, and nondiabetic controls, and also in a prospective cohort of patients receiving mesenchymal stromal cell (MSC) transplantation. NOD mice and adoptive transfer assay were used to dissect the role of the certain B cell subset in disease progression. An in-vitro coculture system of islets with immune cells was established to examine the response against islets and the underlying mechanisms. Results: We identified that plasmablasts, a B cell subset at the antibody-secreting stage, were significantly increased and correlated with the deterioration of beta cell function in patients with new-onset T1D. Further, a fall of plasmablast number was associated with the preservation of beta cell function in patients who received MSC transplantation after 3 months of follow-up. Meanwhile, a gradual increase of plasmablasts in pancreatic lymph nodes during the natural progression of insulitis was observed in non-obese diabetic (NOD) mice; adoptive transfer of plasmablasts together with T cells from NOD mice accelerated diabetes onset in NOD/SCID recipients. Conclusions: Our study revealed that plasmablasts may function as antigen-presenting cells and promote the activation and proinflammatory response of CD4+ T cells, further contributing to the T cell-mediated beta cell destruction. Our results provide insights into the pathogenic role of plasmablasts in islet autoimmunity and may offer new translational strategies for inhibiting T1D development. [ABSTRACT FROM AUTHOR]

Background: We aimed to report pregnancy outcomes of women with type 1 diabetes (T1D) in China, on which data were sparse. Methods: This is a nationwide retrospective study conducted in 11 general medical centers in 8 cities across China. We investigated the clinical data of all women who attended these centers with a singleton pregnancy and whose pregnancy ended between 1 January 2004 and 31 December 2014. Pregnancies of women with pregestational T1D were ascertained and compared with those of women without T1D. Results: From over 300 000 pregnancies over the 11‐year study period, we identified 265 singleton pregnancies of women with T1D. One maternal death was documented among 265 (0.37%) women with T1D and 83 among 318 486 (0.03%) women without T1D. Women with T1D suffered from higher rates of pregnancy loss (13.21% vs 2.92%, crude risk ratio [cRR] 5.08 [95% CI, 3.56‐7.26]) and preeclampsia (17.74% vs 4.20%, cRR 4.94 [95% CI, 3.60‐6.77]) compared with those without T1D. Infants of these women with T1D had elevated rates of neonatal death (5.65% vs 0.16%, cRR 37.36 [95% CI, 21.21‐65.82]) and congenital malformation(s) (8.26% vs 3.53%, cRR 2.46 [95% CI, 1.54‐3.93]) compared with those of women without T1D. No significant improvement in pregnancy outcomes in women with T1D was observed over the period 2004 to 2014. Conclusions: Pregnancy outcomes were persistently poor in women with T1D during 2004 to 2014 in China. Pregnancy care needs to be improved to reduce adverse pregnancy outcomes among Chinese women with T1D. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is characterized pathologically by autoimmune insulitis-related islet β-cell destruction. Although intensive insulin therapy for patients with type 1 diabetes can correct hyperglycemia, this therapy does not prevent all diabetes-related complications. Recent studies have shown that autologous hematopoietic stem cell transplantation ( HSCT) is a promising new approach for the treatment of type 1 diabetes by reconstitution of immunotolerance and preservation of islet β-cell function. Herein we discuss the therapeutic efficacy and potential mechanisms underlying the action of HSCT and other perspectives in the clinical management of type 1 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To assess the efficacy and safety of twice- and thrice-daily biphasic insulin aspart 30 (BIAsp 30) in Chinese subjects with type 2 diabetes inadequately controlled with oral antidiabetes drugs (OADs). RESEARCH DESIGN AND METHODS -- In this 24-week, multicenter, parallel-group, randomized, treat-to-target study, 321 Chinese insulin-naïve subjects with poorly controlled type 2 diabetes (fasting blood glucose ≥ 7.8 mmol/l and A1C ≥ 7.5%) were randomized (1:1) to twice- or thrice-daily (BID and TID groups, respectively) BIAsp 30 without OADs. Initial insulin doses were based on fasting blood glucose at randomization. Insulin dose was adjusted with algorithm-controlled titration to achieve premeal blood glucose of 4.4-6.1 mmol/l. RESULTS -- A1C decreased significantly in both groups (BID group -2.48 ± 0.07%; TID group -2.81 ± 0.07%). Thrice-daily BIAsp 30 showed superiority in A1C improvement (-0.33% [95% CI -0.53 to -0.13]; P < 0.01) and helped more subjects achieve A1C targets <7% (BID group 51.3% vs. TID group 65.8%; P < 0:01). Thrice-daily BIAsp 30 was more effective in subjects with baseline A1C ≥ 9% (<7%: BID group 41.5% vs. TID group 58.3%; P < 0.01). There was no significant difference in rates of overall and nocturnal major and minor hypoglycemia per subject year between groups. No significant differences in weight gain (BID group 3.87 ± 0.28 kg; TID group 4.09 ± 0.27 kg) and mean daily insulin doses (BID group 0.82 ± 0.28 units/kg; TID group 0.86 ± 0.34 units/kg) were observed. CONCLUSIONS -- Twice- and thrice-daily BIAsp 30 were effective in Chinese insulin-naïve subjects with poorly controlled type 2 diabetes. Thrice-daily BIAsp 30 offered greater reduction in A1C without increasing risk of hypoglycemia, insulin dose, and weight gain, especially in subjects with A1C ≥ 9%. [ABSTRACT FROM AUTHOR]

Aim: To investigate the diagnostic utility of corneal confocal microscopy (CCM) for small fiber neuropathy in type 2 diabetes. Materials and Methods: There were 186 participants with type 2 diabetes enrolled in this cross‐sectional research. Pure small fiber neuropathy and mixed fiber neuropathy were defined using clinical examination, electromyography, and quantitative sensory testing. Demographics and clinical data, corneal confocal microscopy parameters, and other neuropathy measures were compared among the groups. The diagnostic utility of corneal confocal microscopy for small fiber neuropathy was assessed by the receiver operating curve. Results: Of the 186 patients, 24.7% had a pure small fiber neuropathy and 17.2% of patients were diagnosed with mixed fiber neuropathy. The corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), and corneal nerve fiber length (CNFL) were significantly lower in subjects with pure small fiber neuropathy compared with those without diabetic peripheral neuropathy (all P < 0.05). The receiver operating curve analysis for corneal confocal microscopy diagnosing small fiber neuropathy demonstrated the area under the curve for CNFD of 0.791, CNFL of 0.778, CNBD of 0.710. Conclusions: Patients with type 2 diabetes with pure small fiber neuropathy showed more corneal nerve loss compared with those without diabetic peripheral neuropathy. It was revealed that corneal confocal microscopy can be a reasonable marker in the diagnosis of small fiber neuropathy in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: The present study was aimed to evaluate the performance and safety of the Glunovo® real-time continuous glucose monitoring system (CGMS) in monitoring interstitial fluid glucose in adult participants with diabetes (at least 18 years old) using venous blood glucose as control. Methods: This was a multicenter, self-controlled clinical trial, conducted in participants with diabetes from China, between March 2019 to October 2019. The CGMS was used by all the participants for a 14-day wear-in period. The real-time glucose values measured by Glunovo® CGMS were compared with venous blood glucose values measured by the Entwicklung, Konstruktion und Fertigung (EKF) blood glucose detector. The primary outcomes were the consistency rate of CGMS readings and venous blood glucose values (20/20% standard). Results: A total of 78 participants (41 men, 37 women) and 156 CGMS sensors were included in the study. Among the included participants, 25 and 53 participants had type 1 and type 2 diabetes, respectively, with median age of 52.50 years (range 32–62 years). The overall agreement rate (20/20%) was 89.71% (95% CI 89.18–90.24%). It was observed that 99.08% (95% CI 98.91–99.24%) and 99.82% (95% CI 99.74–99.89%) of the measuring points fell within the A + B zones of the Clarke error grid analysis and Parkes/consensus error grid analysis, respectively. The mean absolute relative difference was 10.30% ± 4.86%. The probability of a glucose measurement falling within a range, when stratified by venous glucose measurements, ranged from 7.14% for 19.44–22.22 mmol/L to 79.21% for 4.44–6.67 mmol/L. There were 73 (41.24%) and 27 (57.45%) successful CGMS alarms for hypoglycemic and hyperglycemic events, respectively. Conclusion: From the results, Glunovo® CGMS had excellent accuracy and limited clinical risk compared with venous blood glucose in the range of 2.2–22.2 mmol/L over 14 days. [ABSTRACT FROM AUTHOR]

Aims: Cardiovascular autonomic neuropathy (CAN) is one of the most serious types of diabetic autonomic neuropathy and is a class of small fibre neuropathy. Among many inspection methods, quantitative sensory testing is an effective and convenient method for diagnosing diabetic small fibre neuropathy. This cross-sectional study aimed to identify the correlation between the development of cardiovascular autonomic neuropathy and quantitative sensory testing parameters in patients with type 2 diabetes mellitus. Methods: A total of 266 participants with type 2 diabetes mellitus from Nanjing Drum Tower Hospital were enrolled in this study, and each of them received cardiovascular reflex tests (CARTs) and quantitative sensory testing, including testing of cold, warm, cold pain, and heat pain detection thresholds (CDT, WDT, CPT, and HPT, respectively). The results of CARTs were compared with the thermal detection thresholds in quantitative sensory testing by using SPSS 26.0. Results: A total of 266 participants were divided into the CAN group, early CAN (ECAN) group, and without CAN (NCAN) group. There were significant differences in quantitative sensory testing parameters among three groups, and CARTs presented a positive correlation with the WDT and HPT and a negative correlation with the CDT. Moreover, after adjusting for age, sex, diabetes duration, and other influencing factors, WDT, HPT, and CDT were independent risk factors for cardiovascular autonomic neuropathy. Conclusions: The thermal detection thresholds, including cold, warm, and heat pain detection thresholds, in quantitative sensory testing were found to be significantly related to the results of CARTs. Some thermal detection thresholds were independent risk factors for cardiovascular autonomic neuropathy. Therefore, this study showed that quantitative sensory testing has a reliable predictive ability for the occurrence and development of cardiovascular autonomic neuropathy. [ABSTRACT FROM AUTHOR]

Introduction: The clinical characteristics and outcomes of small fiber neuropathy (SFN) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been thoroughly described. In this study, we investigated the metabolic and neurological indexes and the prognosis of patients with T2DM based on skin biopsy. Methods: A total of 34 healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intra-epidermal nerve fiber density (IENFD), and 89 patients with T2DM attending the Nanjing Drum Tower Hospital were evaluated at baseline. Of these 89 patients, 17 with pure SFN and nine with mixed diabetic polyneuropathy (DPN) were reassessed at the end of the follow-up. Results: Glycated hemoglobin and postprandial blood glucose levels were lower (P = 0.005 and P = 0.041, respectively) and postprandial C-peptide and insulin levels were higher (P = 0.001 and P = 0.019, respectively) in the pure SFN group than in the mixed DPN group. A partial correlation study showed that there was a negative correlation between IENFD of the distal leg and cardiovascular autonomic reflex test (CART) scores (r = − 0.513, P = 0.001) after adjusting for age and duration of diabetes. Only vitamin B12 level (P = 0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve (P = 0.045) were increased in the patients with pure SFN at the final visit while MCVs of the common peroneal nerve (P = 0.025) and tibial nerve (P = 0.047) were decreased in the mixed DPN group at the final visit. Conclusion: Better islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. The metabolic and neurological indexes remained relatively stable in the patients with pure SFN during the follow-up. [ABSTRACT FROM AUTHOR]

[Display omitted] Chiglitazar (Carfloglitazar) is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes. In this randomized phase 3 trial, we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen. Eligible patients were randomized (1:1:1) to receive chiglitazar 32 mg (n = 245), chiglitazar 48 mg (n = 246), or sitagliptin 100 mg (n = 248) once daily for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin A 1C (HbA 1c) from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin. Both chiglitazar and sitagliptin significantly reduced HbA 1c at week 24 with values of −1.40%, −1.47%, and −1.39% for chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg, respectively. Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg, with mean differences of −0.04% (95% confidential interval (CI) −0.22 to 0.15) and −0.08% (95% CI −0.27 to 0.10), respectively. Compared with sitagliptin, greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar. Overall adverse event rates were similar between the groups. A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported. The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose. Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. Methods. Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. Results. Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. Conclusion. Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance. [ABSTRACT FROM AUTHOR]

Purpose. Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. Methods. Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. Results. Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. Conclusion. Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) with insulin glargine (Lantus; IGlar) combined with oral antihyperglycaemic medications (OAMs) in insulin‐naive Chinese patients with type 2 diabetes (T2D). Materials and Methods: In this phase III, open‐label trial, adult patients with T2D receiving two or more OAMs at stable doses for 12 weeks or longer, with HbA1c of 7.0% or more and 11.0% or less, were randomized (2:1) to receive once‐daily LY IGlar or IGlar for 24 weeks. The primary outcome was non‐inferiority of LY IGlar to IGlar at a 0.4% margin, and a gated secondary endpoint tested non‐inferiority of IGlar to LY IGlar (−0.4% margin), assessed by least squares (LS) mean change in HbA1c from baseline to 24 weeks. Results: Patients assigned to LY IGlar (n = 359) and IGlar (n = 177) achieved similar and significant reductions (p <.001) in HbA1c from baseline. LY IGlar was non‐inferior to IGlar for change in HbA1c from baseline to week 24 (−1.27% vs. −1.23%; LS mean difference: −0.05% [95% CI, −0.19% to 0.10%]) and IGlar was non‐inferior to LY IGlar. The study therefore showed equivalence of LY IGlar and IGlar for the primary endpoint. At week 24, there were no between‐group differences in the proportion of patients achieving an HbA1c of less than 7.0%, seven‐point self‐measured blood glucose, insulin dose or weight gain. Adverse events, allergic reactions, hypoglycaemia and insulin antibodies were similar in the two groups. Conclusions: Once‐daily LY IGlar and IGlar, combined with OAMs, provide effective and similar glycaemic control with comparable safety profiles in insulin‐naive Chinese patients with T2D. [ABSTRACT FROM AUTHOR]

Improvement of glucose and insulin sensitivity in T2D remains as an unfulfilled task for the treatment of underlying cause of disease. Dorzagliatin is a first-in-class antidiabetic drug that acts as a glucose sensitizer, which repairs the sensor function of glucokinase(GK) and improves glucose sensitivity. The study aimed to confirm the efficacy and safety of dorzagliatin as a monotherapy in T2D patients. In this randomized, double-blind, placebo-controlled trial, 463 eligible drug-naïve Chinese patients were randomized to 75 mg dorzagliatin or placebo (2:1) twice daily (BID) groups for 24 weeks, followed by the dorzagliatin treatment (75 mg BID) for 28 weeks in both groups. The primary endpoint was the change in the HbA1c from baseline to week 24. The mixed models for repeated measures results suggested that the least squares mean change in HbA1c from baseline at week 24 was -1.07% in the dorzagliatin group, significantly lower than the placebo (P<0.0001), with effects sustained till the end of the 52-week treatment. Significantly improved β-cell function was seen at week 24 in the dorzagliatin group measured by the change in homeostasis model assessment 2-β (HOMA2-β) from baseline compared with the placebo group (2.56 vs. -0.72, P<0.05). The homeostatic control rate (HbA1c <7% without hypoglycemia) at week 24, was 42.2% in the dorzagliatin group compared to 17.3% in the placebo group (P<0.0001). No deaths, drug-related serious adverse events, and severe hypoglycemia were reported. Incidence of the clinically significant hypoglycemia (blood glucose <3.0 mmol/L) was low (<1%). Dorzagliatin had a favorable effect on sustained glycemic control and a good safety profile over 52 weeks in Chinese T2D patients. It is the first successful phase 3 trial for a GK activator. As a glucose sensitizer, dorzagliatin targets the restoration of glucose homeostasis, providing new hope for treating T2D patients. Disclosure: L. Chen: None. Y. Zhang: Employee; Self; Hua Medicine. D. Zhu: None. [ABSTRACT FROM AUTHOR]

Introduction: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes. Accurate models for early prediction of GDM are lacking. This study aimed to explore an early risk prediction model to identify women at high risk of GDM through a risk scoring system. Methods: This was a retrospective cohort study of 785 control pregnancies and 855 women with GDM. Maternal clinical characteristics and biochemical measures were extracted from the medical records. Logistic regression analysis was used to obtain coefficients of selected predictors for GDM in the training cohort. The discrimination and calibration of the risk scores were evaluated by the receiver-operating characteristic (ROC) curve and a Hosmer-Lemeshow test in the internal and external validation cohort, respectively. Results: In the training cohort (total = 1640), two risk scores were developed, one including predictors collected at the first antenatal care visit for early prediction of GDM, such as age, height, pre-pregnancy body mass index, educational background, family history of diabetes, menstrual history, history of cesarean delivery, GDM, polycystic ovary syndrome, hypertension, and fasting blood glucose (FBG), and the total risk score also including FBG and triglyceride values during 14–20 gestational weeks. Our total risk score yielded an area under the curve (AUC) of 0.845 (95% CI = 0.805–0.884). This performed better in an external validation cohort, with an AUC of 0.886 (95% CI = 0.856–0.916). Conclusion: The GDM risk score, which incorporates several potential clinical features with routine biochemical measures of GDM, appears to be a sensitive and reliable screening tool for earlier detection of GDM risk. [ABSTRACT FROM AUTHOR]

Background/Aims: Roux-en-Y gastric bypass (RYGB) is one of the most effective therapies for morbid obesity, yet some patients who have taken the surgery still undergo insufficient weight loss. Visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI), and cardiometabolic index (CMI) have been regarded as clinical indicators of adiposity phenotypes that associated closely with obesity-related metabolic diseases. However, no studies have evaluated the relationship between these indexes and weight loss after bariatric surgery. In this prospective study, we aimed to evaluate whether VAI, LAP, BAI, and CMI would predict postoperative weight loss outcomes after RYGB. Methods: This study included 38 men and 67 women who have undergone RYGB between January 2017 and May 2018 and recorded their %TWL (percent of total weight loss), %EBMIL (percent of excess body mass index loss), %EWL (percent of excess weight loss), anthropometric indices, and biochemical parameters before and 12 months after the surgery. In addition, VAI, LAP, BAI, and CMI were measured with anthropometric measures or lipid profiles using related equations and analyzed with metabolic characteristics. Results: Subjects with lower BAI (<32.54 in men and 37.39 in women) displayed higher %EBMIL and %EWL 12 months after surgery. BAI was independently associated with %EWL 12 months after surgery in both men and women (both p < 0.05). The area under the receiver operating characteristic curve for BAI was significantly higher (0.773 in men and 0.818 in women) than VAI, LAP, and CMI. Conclusions: BAI serves as a reliable surrogate marker of the weight loss outcome after RYGB. The predictivity of adiposity indexes in beneficial outcomes after weight loss therapies is of important referential value for the implementation and optimization of individualized and refined weight loss treatments for obese patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure.Research Design and Methods: A comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities.Results: The rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13-0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09-0.52]).Conclusions: The substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries. [ABSTRACT FROM AUTHOR]

Aims. Epidemiological data on diabetic retinopathy (DR) in Chinese population is still rather scarce, and risk factors for diabetic retinopathy are inconsistent because of study designs, grading standards, and population samples. Materials and Methods. This hospital-based retrospective study included 1052 type 2 diabetes patients. Diabetic retinopathy was diagnosed by nonmydriatic fundus photography and/or fundus examination apparatus. Logistic regression analysis was performed to evaluate the risk of diabetic retinopathy. Results. A total of 352 (33.5% prevalence) subjects were diagnosed with diabetic retinopathy based on our population. The patients in the DR group not only had significantly higher hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), urinary microalbumin-creatinine ratio (ACR), and systolic blood pressure but also had higher follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels compared to those in the non-DR group. Moreover, we confirmed that diabetes duration and HbA1c are strongly associated with DR risk. We also found that serum LH was an independent risk factor in male diabetic retinopathy patients (OR = 1.086 , 95% CI 1.024–1.152), and the levels of LH were significantly associated with diabetic retinopathy prevalence (P = 0.018). Conclusions. Our study strengthens the argument that diabetes duration and HbA1c are risk factors for patients with DR. Additionally; we firstly confirmed that serum LH was an independent risk factor in male diabetic retinopathy patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the risk of perinatal outcomes in pre-gestational type 1 diabetes mellitus (T1DM) compared to gestational diabetes mellitus (GDM) and pregnancy without diabetes and to examine the association of glycemic level of third-trimester gestation with perinatal outcomes in T1DM. We included 69 pre-gestational T1DM, 1398 cases of GDM, and 1304 control pregnancies and collected data regarding demographics, obstetric, and perinatal outcomes from the hospital discharge database. Relative to the pregnancies without diabetes, women with T1DM encountered increasing risk of polyhydramnios, preterm delivery, and cesarean section. These adverse outcomes were also common in GDM, although with relatively lower adjusted ORs. The weights of babies delivered by women with T1DM were more intend to be large for gestational age, as well as to be less than 2.5 kg relative to those without diabetes. Poorly controlled hemoglobin A1c in late pregnancy was significantly associated with an increased risk of preterm birth in T1DM (adjusted odds ratio 2.01, 95%confidence interval 1.1–3.6). Women with T1DM have considerably increased risks of adverse perinatal outcomes, which appear more prevalent than the perinatal outcomes in women with GDM. Thus, a specific routine is required for pregnancy in T1DM to improve the glycemic control and obstetric care. [ABSTRACT FROM AUTHOR]