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Aim: To compare the efficacy and safety of a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs). Methods: In Soli‐D, a 24‐week, multicentre, open‐label, study, insulin‐naïve adults were randomized 1:1 to once‐daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium‐glucose co‐transporter‐2 inhibitors. The primary endpoint was non‐inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed. Results: At week 24, iGlarLixi showed non‐inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: −0.20 [95% confidence interval {CI}: –0.33, −0.07]; P <.001 for non‐inferiority; [97.5% CI: –0.35, −0.05]; P =.003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of −1.49 kg in favour of iGlarLixi (97.5% CI: –2.32, −0.66; P <.001). Event rates (per person‐year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported. Conclusions: In Chinese people with T2D suboptimally controlled with OADs, once‐daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China. Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression. Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345– 1.957) and 1.990 (95%CI: 1.709– 2.316) in women with NAFLD, compared with the subjects without NAFLD. Conclusions: NAFLD is independently associated with increased risk of CVD development. [ABSTRACT FROM AUTHOR]

Introduction: Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post‐challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2‐h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population. Methods: Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model. Results: Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811–0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786–0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635–0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app‐iphds‐e1fc405c8a69.herokuapp.com/. Conclusions: The proposed IPHDS could be a convenient and user‐friendly screening tool for diabetes during health examinations in a large general population. [ABSTRACT FROM AUTHOR]

Objective: Several studies have demonstrated a significant association between the presence of the ear lobe crease (ELC) and cardiovascular disease. Advanced glycation end‐products (AGEs) can affect the structures and functions of proteins and contribute to the development of diabetic complications. However, few studies have reported the relationship between AGEs and ELC. The purpose of this study was to investigate the correlation of skin autofluorescence (SAF)‐AGEage (SAF‐AGEs × age/100) with ELC. Methods: This cross‐sectional study enrolled 6500 eligible participants from two communities in Beijing. Skin autofluorescence (SAF) was used to measure skin AGEs (SAF‐AGEs). SAF‐AGEage was defined as AGEs × age/100. Binary logistic regression analysis and linear regression analysis nested in logistic models were applied to test outcomes. Results: The overall prevalence of ELC with an average age of 62.7 years participants was 57.1% (n = 3714). Age, fasting blood glucose, systolic blood pressure, and lipoprotein cholesterol were all greater in participants with ELC. ELC‐positive participants had higher prevalence of coronary heart disease. Logistic analysis showed a significantly positive relationship between quartiles of SAF‐AGEage and ELC (odds ratio [OR] 1.526, 95% CI 1.324–1.759; OR 2.072, CI 1.791–2.396; and OR 2.983, CI 2.551–3.489) for the multivariate‐adjusted models, respectively. Stratified research revealed that those with a history of diabetes, hypertension, or coronary heart disease experienced the connection between SAF‐AGEage and ELC. Conclusion: ELC is associated with coronary heart disease, and the SAF‐AGE has a potential role in ELC development in elder people. [ABSTRACT FROM AUTHOR]

The Soli-D randomized controlled clinical trial in Diabetes, Obesity & Metabolism compared the efficacy and safety of insulin glargine 100 U/mL + lixisenatide (iGlarLixi) versus insulin degludec + insulin aspart (IDegAsp) in Chinese people with type 2 diabetes. The study found that iGlarLixi had a greater reduction in average postprandial glucose (PPG) levels from self-measured plasma glucose (SMPG) compared to IDegAsp. The strongest effect of iGlarLixi on PPG was observed with the first meal of the day, but it also demonstrated clinically relevant reductions in PPG after all meals. The results align with previous studies of iGlarLixi, which also showed reductions in PPG levels. Both iGlarLixi and IDegAsp effectively addressed PPG in Chinese people with type 2 diabetes. [Extracted from the article]

Background: Triglyceride glucose index (TyG index) was related with both type 2 diabetes (T2DM) and hypertension (HTN). Prospective studies linking the TyG index to the incidence of T2DM and HTN comorbidity remain unclear. This study aimed to to explore the longitudinal association between TyG and new-onset T2DM with HTN. Methods: 4,434 subjects (1249 males and 3185 females) without initial T2DM and HTN were followed up for 7 years. This study was conducted from November 2011 to August 2018 in the Gucheng, Laoshan and Jinding communities of Beijing. The incidence of T2DM with HTN during the 7-year follow-up was identified as the endpoint. The TyG index was divided into four quartiles: the < 25% level, the 25–50% level, the 50–75% level and the ≥ 75% level. The relationships between the TyG index and T2DM with HTN were evaluated by Cox proportional hazards regression models. Results: During 7 years, the augmented trend of T2DM with HTN was observed in the participants. After adjusting for all confounding factors, compared with those in the lowest quartile of TyG index, the population in the highest quartile of TyG index had a higher risk of T2DM with HTN (hazard ratio (HR), 2.878; 95% confidence intervals (95% CI), 1.230–6.731, P = 0.015), however, the association remained significant only in the female population (HR 2.753, 95% CI, 1.061–7.139, p = 0.037). The TyG had superior predictive ability of increased risk of T2DM with HTN for the populations of older age (≥ 65 years) (HR 2.694, 95% CI 1.212–5.989, p = 0.015), higher eGFR (≥ 90 mL/(min·1.73 m2)) (HR 2.603, 95% CI 1.164–5.818, p = 0.020) or obesity (BMI ≥ 28 kg/m2) (HR 2.547, 95% CI 1.001–6.478, p = 0.020). Conclusion: A population with a higher TyG index level was more likely to have an enhanced incidence of T2DM and HTN comorbidity. TyG index could have the significance of clinical in early protection against T2DM with HTN. [ABSTRACT FROM AUTHOR]

Background: The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by "Life's Essential 8" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife "Life's Essential 8" CVH status with cardiometabolic outcomes in a Chinese cohort. Methods: The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in "Life's Essential 8" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. Results: 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04–1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25–1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01–2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90–2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. Conclusions: Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population. [ABSTRACT FROM AUTHOR]

Key Points: Question: How does once-weekly insulin icodec compare with once-daily insulin degludec in glucose-lowering efficacy (hemoglobin A1c [HbA1c]) in people with insulin-naive type 2 diabetes? Findings: In this randomized, double-masked, double-dummy trial that enrolled 588 people with type 2 diabetes, estimated mean HbA1c change from baseline to week 26 was noninferior with insulin icodec (−1.6 percentage points) compared with insulin degludec (−1.4 percentage points), with confirmed statistical superiority (estimated treatment difference, −0.2 percentage points). Meaning: The results demonstrate the efficacy of once-weekly insulin icodec treatment in people with insulin-naive type 2 diabetes. Importance: Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes. Objective: To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes. Design, Setting, and Participants: Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol). Interventions: Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294). Main Outcomes and Measures: The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes. Results: Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], −0.2 [95% CI, −0.3 to −0.1] percentage points), confirming noninferiority (P <.001) and superiority (P =.002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, −6 to 5] mg/dL; P =.90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, −0.19 to 1.10] kg; P =.17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P =.11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P =.01). Conclusions and Relevance: Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups. Trial Registration: ClinicalTrials.gov Identifier: NCT04795531 This randomized clinical trial examines the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short‐term intensive insulin therapy (SIIT) during study run‐in (prior to randomization) using a basal‐first insulin titration method. Materials and methods: This was exclusively an exploratory analysis of the 7‐ to 10‐day run‐in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once‐daily insulin glargine and three‐times‐daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre‐meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2‐hour postprandial blood glucose (PBG) targets. Results: Overall, 397 entered the run‐in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2‐hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2‐hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2‐hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. Conclusions: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2‐3 oral antihyperglycaemic drugs (OADs) with twice‐daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short‐term intensive insulin therapy in adults with type 2 diabetes in China. Materials and Methods: This open‐label trial enrolled insulin‐naïve adults with type 2 diabetes and an HbA1c of 7.5%‐11.0% (58‐97 mmol/mol) despite treatment with 2‐3 OADs. All participants stopped previous OADs except MET, then received short‐term intensive insulin therapy during the run‐in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2‐hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase‐4 inhibitor or twice‐daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint). Results: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non‐inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of –1.72% and –1.70% (–42.2 and –42.1 mmol/mol), respectively (estimated difference –0.01%; 95% CI –0.20%, 0.17% [–0.1 mmol/mol; 95% CI –2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P =.003), symptomatic (19% vs. 31%; P =.007) or confirmed hypoglycaemia (18% vs. 33%; P <.001) was lower in the Gla + OADs group. Conclusions: Compared with Asp30 + MET, Gla + 2‐3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short‐term intensive insulin therapy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Mesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications. Methods: Preconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague–Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group. Results: The secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-α, IL-1β) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs. Conclusion: Diabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity are well-known risk factors for type 2 diabetes mellitus (T2DM). The effect of the maximum body mass index (BMImax), which indicates the highest body weight before the diagnosis of T2DM, is not fully understood. This study aimed to explore the predictive value of BMImax in the progression of diabetes. Methods: This prospective study recruited 2018 subjects with normal glucose tolerance in Beijing, China. The subjects were followed up for eight years, and the association between BMImax and glucose outcomes was evaluated. Results: Ninety-seven of the 2,018 participants developed diabetes by the end of the study. Compared to individuals with normal glucose tolerance, those who developed diabetes were characterized by higher levels of fasting plasma glucose (FPG), 2 h postload glucose (PBG), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-c), a higher prevalence of a familial history of diabetes and a lower level of high‐density lipoprotein cholesterol (HDL-c). Multivariate regression analysis of sex-stratified groups suggested that FPG, HbA1c, SBP and familial history of diabetes were independent risk factors for diabetes, but that BMImax was a unique indicator for female patients. Conclusions: BMImax might be an independent predictor of T2DM in females, but it does not seem to be associated with the risk of diabetes in males. BMImax could be regarded as an indicator in the prevention and management of diabetes. [ABSTRACT FROM AUTHOR]

Background: Obesity can lead to the development of type 2 diabetes mellitus (T2DM). However, the predictive power of different obesity anthropometric indices (ObAIs) for T2DM varies with race and geographical area. Therefore, the study aimed to investigate the association between different ObAIs and T2DM and determine the best index for screening T2DM in middle-aged and elderly men and women in Beijing, China. Methods: A cross-sectional study was conducted in Shijingshan district (Beijing, China) from November 2011 to August 2012, involving a total of 14,558 subjects aged ≥ 40 years. Data on demographic information, lifestyle, history of T2DM, hypertension and dyslipidemia were collected. Body height, body weight, waist circumference (WC), hip circumference, and blood pressure were recorded. The oral glucose tolerance test or a standard meal test and blood lipid test were performed. The relationship between different ObAIs and T2DM was analyzed using multiple logistic regression. Results: After adjustment for age, smoking status, alcohol intake, occupation and education degree, diabetes family history, hypertension and dyslipidemia, body mass index (BMI), WC, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were positively associated with T2DM in both men and women. Compared with the lowest BMI, WC, WHR, and WHtR quartiles, ORs of the highest quartiles were 2.131 (95% CI: 1.465– 3.099), 1.752 (95% CI: 1.270– 2.417), 1.342 (95% CI: 1.072– 1.678), 2.739 (95% CI: 2.293– 3.271) in men and 1.837 (95% CI: 1.584– 2.130), 3.122 (95% CI: 1.980– 4.924), 3.781 (95% CI: 2.855– 5.007), 2.379 (85% CI: 2.040– 2.775), respectively, in women. The areas under ROC curve of BMI, WC, WHR, and WHtR for men were 0.584 (95% CI: 0.568– 0.600), 0.509 (95% CI: 0.492– 0.525), 0.501 (95% CI: 0.485– 0.518), and 0.642 (95% CI: 0.627– 0.658) and 0.619 (95% CI: 0.607– 0.632), 0.709 (95% CI: 0.697– 0.720), 0.741 (95% CI: 0.730– 0.752), and 0.654 (95% CI: 0.642– 0.666), respectively, for women. Conclusion: WHtR and WHR have been found to perform better as predictors of T2DM in middle-aged and elderly Chinese men and women, respectively. [ABSTRACT FROM AUTHOR]

Background: Albuminuria has been widely considered a risk factor for cardiovascular diseases (CVDs), which is associated with hypertension (HTN), type 2 diabetes mellitus (T2DM), HTN with T2DM, and dyslipidemia. However, the associations between albuminuria and HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs are still unclear. Thus, this study aimed to explore the association of albuminuria thoroughly, especially within the normal range, with the abovementioned diseases in the Chinese population. Methods: This study included 40,188 participants aged over 40 years from seven centers across China. Urinary albumin–creatinine ratio (UACR) was firstly divided into the ≥30-mg/g group, indicating kidney damage, and <30-mg/g group. Furthermore, UACR was divided into five groups: the <20%, 20%–39%, 40%–59%, 60%–79%, and ≥80% groups, according to the quintile division of participants within the normal range. Propensity score matching was used to reduce bias, and multiple logistic regression models were conducted to examine the association between UACR and HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs. Results: Multivariable regression analysis revealed that UACR, even within the normal range, is significantly associated with HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs, and the association between UACR and HTN with T2DM was the most significant in model 3 even after adjusting for confounding factors (HTN: OR = 1.56 (95% CI = 1.45–1.68), p < 0.0001; T2DM: OR = 1.78 (95% CI = 1.60–1.97), p < 0.0001; HTN with T2DM: OR = 1.76 (95% CI = 1.59–1.95), p < 0.0001; dyslipidemia: OR = 1.08 (95% CI = 1.01–1.14), p = 0.0146; CVDs: OR = 1.12 (95% CI = 1.00–1.25), p = 0.0475). In the stratified analysis, high normal UACR was significantly associated with HTN, T2DM, HTN with T2DM, and dyslipidemia in subgroups. Conclusions: In summary, we observe a higher prevalence of HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs in abnormal UACR and reveal a significant association of UACR, even within the normal range, with HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs. [ABSTRACT FROM AUTHOR]

Hundreds of research and review articles concerning genome-wide association study (GWAS) in diabetes have been published in the last two decades. We aimed to evaluate the hotspots and future trends in GWAS in diabetes research through bibliometric analysis. Accordingly, 567 research and review articles published between 2001 and 2021 were included. A rising trend was noted in the annual number of publications and citations on GWAS in diabetes during this period. Harvard University and Harvard Medical School have played leading roles in genome research. Hotspot analyses indicated that DNA methylation and genetic variation, especially in type 2 diabetes mellitus, are likely to remain the research hotspots. Moreover, the identification of genetic phenotypes associated with adiposity, metabolic memory, pancreatic islet, and inflammation is the leading trend in this research field. Through this review, we provide predictions on the main research trends in the future so as to shed light on new directions and ideas for further investigations on the genetic etiology of diabetes for its prevention and treatment. [ABSTRACT FROM AUTHOR]

Interferon (IFN) is a broad-spectrum antiviral agent that activates cell surface receptors and causes cells to produce antiviral proteins, inhibiting viral replication. Interferon use has long been associated with diabetes. The PubMed database was searched for articles related to diabetes and interferon from March 30, 2020. Patients were divided into type 1 diabetes group and type 2 diabetes group. We reviewed the relevant literature to compare interferon-associated T1D and interferon-associated T2D differences. Interferon treatment shortened the incubation period of T2D and changed the original T2D to T1D. The onset of interferon-associated T1D required longer periods of IFN treatment than interferon-associated T2D, and the interferon-associated T1D group had higher GADA positive rates, lower BMI, lower fasting blood glucose, and greater insulin dependence (p<0.05). More patients in the T1D group were positive for HLA-DRB1*04, DRB1*03, DRB1*09, DRB1*14, HLA-DQB1*04, HLA-DQB1*02, HLA-DQB1*03, and HLA-DQB1*05. The combined detection of GAD antibodies and HLA alleles may be an effective method to predict the incidence of T1D after IFN treatment. [ABSTRACT FROM AUTHOR]

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Aim: To assess the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (degludec) in Chinese people with type 2 diabetes (T2D) treated with basal insulin. Materials and Methods: In DUAL II China, a randomized, double‐blinded, multicentre, treat‐to‐target trial, Chinese adults with T2D and HbA1c of 7.5% or more on basal insulin and metformin, with or without other oral antidiabetic drugs (OADs), were randomized 2:1 to 26 weeks of treatment with either IDegLira (max. dose 50 U degludec/1.8 mg liraglutide) or degludec (max. 50 U/day), respectively, combined with metformin. At 26 weeks, superiority of IDegLira over degludec was assessed for change in HbA1c (primary endpoint), and body weight and number of severe or blood glucose (BG)‐confirmed hypoglycaemic episodes (confirmatory secondary endpoints). Results: Overall, 453 participants were randomized to IDegLira (n = 302) or degludec (n = 151). Superiority was confirmed for IDegLira over degludec in HbA1c change (−1.9% vs. −1.0%, respectively, estimated treatment difference [ETD] [95% confidence interval]: −0.92% [−1.09; −0.75], P <.0001), body weight change (−0.7 vs. +0.4 kg, respectively, ETD [95% CI]: −1.08 kg [−1.63; −0.52], P =.0002) and severe or BG‐confirmed hypoglycaemia (estimated rate ratio [95% CI]: 0.53 [0.30; 0.94], P =.0297). The odds of achieving HbA1c less than 7.0% without hypoglycaemia and/or weight gain were greater with IDegLira than degludec (P <.0001 for all). Daily insulin dose at 26 weeks was lower for IDegLira (34.3 U) than degludec (37.4 U) (P =.0014). No unexpected safety signals were observed. Conclusions: IDegLira may be an efficacious and well‐tolerated treatment intensification option for Chinese people with T2D uncontrolled on basal insulin and OADs. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to evaluate the associations of metabolic abnormalities with incident diabetic kidney disease (DKD) and to explore whether dyslipidaemia, particularly high fasting triglyceride (TG), was associated with the development of DKD. Methods: In total, 11 142 patients with new‐onset type 2 diabetes with baseline estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2 were followed up during 2011‐2016. Incident DKD was defined as eGFR <60 mL/min/1.73 m2 at follow‐up. Multiple logistic regression analysis was conducted to explore the relationship of metabolic abnormalities at baseline and at follow‐up with risks of DKD. High TG was defined by TG ≥1.70 mmol/L. Low high‐density lipoprotein cholesterol (HDL‐c) was defined by HDL‐c <1.0 mmol/L for men or <1.3 mmol/L for women. Results: Participants who developed DKD had higher levels of waist circumference and systolic blood pressure, and lower levels of HDL‐c at both baseline and follow‐up visits. The DKD group also had higher levels of post‐load plasma glucose and TG at follow‐up. Multivariate logistic regression analysis revealed that both high TG at baseline [odds ratio (OR) = 1.37, p =.012) and high TG at follow‐up (OR = 1.71, p <.001) were significantly associated with increased risks of DKD. Patients with high TG levels at both baseline and follow‐up had higher risk of DKD compared with constantly normal TG (OR = 1.65, p <.001) after adjustment for covariates. Conclusions: In a large population of patients with new‐onset type 2 diabetes, a high TG level was an independent risk factor for the development of DKD. Tight TG control might delay the occurrence of DKD. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether the cardiorenal benefits of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin are affected by body mass index (BMI) in type 2 diabetes patients with established cardiovascular (CV) disease, including Asians. Methods: In this exploratory analysis of the EMPA‐REG OUTCOME trial, we used Cox regression to evaluate the effects of empagliflozin on all‐cause mortality, hospitalization for heart failure (HHF) or CV death, and incident or worsening nephropathy by baseline BMI category. Results: Of the 7020 participants (1517 Asians [21.6%]), 934 (13.3%), 2465 (35.1%) and 3621 (51.6%) had a BMI of less than 25, 25 to less than 30, and 30 kg/m2 or higher, respectively. Overall, hazard ratios for empagliflozin versus placebo for all‐cause mortality, HHF or CV death, and incident or worsening nephropathy were 0.68 (95% CI 0.57, 0.82), 0.66 (0.55, 0.79) and 0.61 (0.53, 0.70), respectively, and were consistent across BMI categories (P values for interaction between treatment and BMI were.6772,.3087 and.6265, respectively). Results were similar in Asians using these BMI categories and categories of less than 24, 24 to less than 28, and 28 kg/m2 or higher. Conclusion: Empagliflozin reduced cardiorenal and mortality risk regardless of BMI at baseline, including in Asians with a lower BMI. [ABSTRACT FROM AUTHOR]

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

Background. Previous studies have shown that the ratio of triglyceride to high-density lipoprotein cholesterol level (TG/HDL-C) is a risk factor for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the nonlinear relationship between TG/HDL-C and the incidence of T2DM in a Chinese population. Methods. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the incidence of T2DM among 7,791 participants from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) cohort study at baseline. Results. After adjusting for age, sex, body mass index, smoking status, alcohol intake, low-density lipoprotein cholesterol level, strenuous activity, education level, family histories of T2DM and tumors, and the presence of hypertension, tumor, stroke, and coronary heart disease, we showed that TG/HDL-C was positively associated with the incidence of T2DM at the 4-year follow-up (OR = 1.49 , 95 % CI = 1.26 – 1.78). TG/HDL-C and incidence of T2DM showed a nonlinear relationship; the inflection point of TG/HDL-C was 1.50. The ORs (95% CI) on the left and right sides of the inflection point were 2.50 (1.70–3.67) and 0.96 (0.67–1.37), respectively. After adjusting for age, sex, and body mass index (BMI) in the linear relationship, the OR of the incidence of T2DM was 1.60 (95 % CI = 1.37 – 1.87). When the TG/HDL-C was less than 1.50 or greater than 1.76, the ORs (95% CI) were 2.41 (1.82–3.18) or 0.81 (0.53–1.25), respectively. Subgroup analysis showed no relationships of T2DM incidence with sex, BMI, family history of T2DM, or TG/HDL-C. Conclusion. TG/HDL-C is positively associated with diabetes risk. In our study, with each increasing quintile, the risk of T2DM after 4 years was 1.60 or 1.49 depending on the variables adjusted. In addition, our cohort study showed a nonlinear relationship between TG/HDL-C and T2DM incidence, with an inflection point of 1.76 or 1.50, depending on the variables adjusted. When the TG/HDL was less than 1.50, the ORs (95% CI) were 2.41 (1.82–3.18) and 2.50 (1.70–3.67). When the TG/HDL-C was greater than 1.76 or 1.50, there was no significant difference in the change in OR. [ABSTRACT FROM AUTHOR]

Aims/Introduction: This secondary analysis of the 24‐week SMART study examined the efficacy of add‐on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus, based on baseline characteristics. Materials and Methods: Randomized patients (n = 481) were classified into subgroups based on their baseline age (<65, ≥65 years), body mass index (BMI; <24, 24–<28, ≥28 kg/m2), glycated hemoglobin (HbA1c; <8%, 8–<9%, 9–<10%, ≥10%) and renal function (creatinine clearance 50–<80, ≥80 mL/min). Treatment effects on primary outcome (HbA1c) and key secondary outcomes of fasting plasma glucose (FPG), 2‐h postprandial glucose and homeostatic model assessment of β‐cell function were assessed across patient subgroups. Results: For saxagliptin, reductions in HbA1c from baseline to week 24 were consistent across different subgroups regardless of baseline age, body mass index, HbA1c and renal function (range −0.66 to −1.16%). Saxagliptin was associated with consistent reductions in FPG (−0.60 to −1.33 mmol/L) and 2‐h postprandial glucose (−0.48 to −1.95 mmol/L) across the majority of subgroups studied. The efficacy of acarbose on FPG attenuated progressively with increasing baseline HbA1c (+0.86 to −1.43 mmol/L); an increase from baseline FPG was observed in patients with HbA1c >9%. The effect of acarbose on postprandial glucose was also variable (+0.23 to −3.38 mmol/L). Conclusions: As add‐on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, body mass index and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%). [ABSTRACT FROM AUTHOR]

Introduction: Many Chinese patients who are uncontrolled by oral antidiabetic drugs (OADs) receive short-term intensive insulin therapy (IIT) in hospital to rapidly relieve glucose-associated toxicity and to preserve/improve β-cell function. However, evidence for optimizing insulin algorithms for maintenance treatment after IIT is lacking. This study will compare the efficacy and safety of basal insulin-based treatment versus twice-daily premixed insulin in type 2 diabetes mellitus (T2DM) patients after short-term in-hospital IIT.Methods: This 26-week randomized, multicenter, positive-controlled, open-label, parallel-group study will enroll approximately 400 male and female patients aged 18-70 years with poorly-controlled T2DM (HbA1c > 7.5%) despite treatment with metformin plus at least one other OAD for 8 or more weeks. During a run-in period of 7-10 days, patients will be treated in-hospital with IIT comprising insulin glargine (Lantus®) once daily and insulin glulisine (Apidra®) three times daily; both regimens will be titrated daily to achieve the glycemic goal. Eligible patients will then be randomized in a 1:1 ratio to insulin glargine plus OADs or twice-daily premixed insulin (NovoLog® Mix 70/30) for 24 weeks, with metformin maintained throughout the study in both treatment groups. The primary endpoint is HbA1c change from baseline to week 24. Secondary endpoints include assessment of fasting plasma glucose, total daily insulin dose, hypoglycemia incidence, body weight change, adverse events, and patient satisfaction.Discussion: Given the current lack of clinical data, this study will provide evidence supporting safe and effective glycemic control using basal insulin glargine-based therapy plus OADs compared with twice-daily premixed insulin in Chinese patients with T2DM after short-term IIT. This will assist physicians by providing a wider choice of treatments.Trial Registration: ClinicalTrials.gov identifier, NCT03359837 (registered on 2 December 2017). [ABSTRACT FROM AUTHOR]

Introduction: The effect of dipeptidyl peptidase-4 (DDP-4) inhibitors versus α-glucosidase inhibitors (AGIs) on the treatment of type 2 diabetes mellitus (T2DM) in a real-world setting is unknown. The aim of this real-world study was to compare the glucose-lowering effect and tolerability of vildagliptin as add-on to metformin monotherapy (VM) and AGI as add-on to metformin monotherapy (AM) in Chinese patients with T2DM. Methods: This was a subgroup analysis of the China Prospective Diabetes Study, a post-marketing, prospective, observational, real-world study conducted at 52 centers in China. T2DM patients with inadequate glycemic control on metformin monotherapy who received VM or AM were included. The composite primary endpoint was glycemic control (hemoglobin A1c [HbA1c] < 7%) after 12 months in the absence of tolerability events (hypoglycemia, weight gain ≥ 3%, or gastrointestinal events leading to treatment discontinuation). Propensity score matching (PSM) was used to balance the two groups. Results: The success rates of the composite endpoint were higher in the VM group (n = 604/159 before/after PSM) than in the AM group (n = 159/157 before/after PSM), but the difference was not statistically significant (before PSM: 53.0 vs. 46.5%, P = 0.148; after PSM: 56.7 vs. 45.9%, P = 0.055). The glycemic control rate and HbA1c reduction were similar between groups at 3, 6, and 12 months. Compared with the AM group, the VM group had lower risks of any tolerability event (relative risk [RR] 0.53, 95% confidence interval [CI] 0.33–0.83, P = 0.006), of any adverse event (AE) (RR 0.64, 95% CI 0.41–1.00, P = 0.049), and of any serious AE (RR 0.45, 95% CI 0.25–0.81, P = 0.007). Conclusion: The results of this real-world study suggest that vildagliptin as add-on to metformin monotherapy had a similar glucose-lowering effect to AGI as add-on to metformin monotherapy, but with better safety. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is increasingly common among patients with type 2 diabetes mellitus (T2DM). The two conditions can act synergistically to produce adverse outcomes. However, the therapeutic options for patients with NAFLD and T2DM are currently limited. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown therapeutic potential for diabetes and hepatic disorders such as liver cirrhosis and fulminant hepatic failure. The present study is aimed at investigating the effect of human UC-MSCs on a mouse model of NAFLD and T2DM, characterized by obesity-induced hyperglycaemia, dyslipidaemia, hepatic steatosis, and liver dysfunction. Thirty-week-old male C57BL/6 db/db mice were infused with human UC-MSCs or phosphate-buffered saline (PBS) via the tail vein once a week for six weeks. Age-matched male C57BL/6 wild-type db/+ mice were used as controls. Body weight and random blood glucose were measured every week. One week after the sixth infusion, intraperitoneal glucose tolerance tests and insulin tolerance tests were performed and the blood and liver were harvested for biochemical and histopathological examinations. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence staining, and western blot were performed to monitor the expression of the lipid metabolism- and regulatory pathway-related genes. UC-MSC infusions significantly ameliorated hyperglycaemia, attenuated the elevation of hepatic transaminases, and decreased lipid contents, including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Moreover, histological lesions in the liver diminished markedly, as evidenced by reduced lipid accumulation and attenuated hepatic steatosis. Mechanistically, UC-MSCs were found to regulate lipid metabolism by increasing the expression of fatty acid oxidation-related genes and inhibiting the expression of lipogenesis-related genes, which were associated with the upregulation of the HNF4α-CES2 pathway. Our results demonstrate that human UC-MSCs can ameliorate NAFLD and reverse metabolic syndrome in db/db mice. Thus, UC-MSCs may serve as a novel therapeutic agent for T2DM patients with NAFLD. [ABSTRACT FROM AUTHOR]

Background. In patients with type 2 diabetes mellitus (T2DM) and poor glycemic control receiving metformin (MET), glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended as the adjunctive therapy. However, there are only a few studies involving the comparative effects of exenatide twice a day (EXBID) and exenatide once weekly (EXQW) on HOMA-β. This meta assessed the comparative effects of EXQW and EXBID on HOMA-β among T2DM patients. Materials and Methods. PubMed, Cochrane Library, and Embase databases were searched to collect randomized controlled trials (RCTs). Network meta-analysis was performed, and network diagrams were constructed to evaluate the effects. The primary outcome is HOMA-β, and the secondary outcomes are fasting blood glycose (FBG), glycated hemoglobin (HbA1c), and weight loss. Results. A total of 8 studies with 3506 subjects were included. Compared with other antidiabetic agents, EXQW has a greater improvement in HOMA-β than EXBID (weight mean difference WMD=‐0.46, 95% confidence interval (CI) [-0.64, -0.28], P=0.001). The effect of EXQW on HbA1c is superior to that of sitagliptin (SITA) (WMD=0.51, 95% CI [0.03, 0.99], P=0.037). The significant reduction of weight was detected for EXBID in comparison with EXQW (WMD=‐0.73, 95% CI [-1.13, -0.33], P=0.001), and no significant difference was found between EXQW and MET. Conclusions. EXQW shows a greater improvement in HOMA-β than EXBID. Moreover, the efficacy of EXQW on glycemic control is similar to other antidiabetic agents including EXBID. It is an advisable treatment for diabetic patients to improve HOMA-β and has an advantage of fewer number of injections compared with EXBID, to increase patients' adherence and quality of life. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy and safety of vildagliptin alone or with metformin is well established by randomized trials, but it is unknown whether it can be extrapolated to the real-world setting in Chinese patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness and safety of vildagliptin add-on to metformin versus dual oral antidiabetes drug (OAD), non-vildagliptin combination therapies in real-world Chinese patients with T2DM. Methods: The China Prospective Diabetes Study was a post-marketing, prospective, multicenter, observational, real-world study conducted in 52 centers. Patients inadequately controlled with OAD monotherapy and who initiated vildagliptin add-on to metformin (VM cohort) or two OADs other than vildagliptin (comparator cohort) were included for the present analysis. The composite primary endpoint was glycated hemoglobin (HbA1c) < 7% and without tolerability events (hypoglycemia, weight gain ≥ 3%, or discontinuation due to gastrointestinal events) at 12 months. Secondary endpoints included change in HbA1c from baseline, subgroup analysis, and tolerability. Propensity score matching analysis was performed to adjust for baseline covariates imbalance (body mass index (BMI) and HbA1c). Results: A total of 604 patients received VM and 670 received comparator therapy. Patients who received VM were younger, more obese, and had a higher baseline HbA1c and a shorter duration of T2DM. After propensity score matching, there were 530 patients per cohort. After 12-month treatment, the success rates of the composite primary endpoint were 50.9% and 33.0% in the VM and comparator cohorts, respectively (P < 0.001; odds ratio = 2.10, 95% confidence interval (CI) 1.64–2.70). Furthermore, the success rates of the composite endpoint were higher with VM across geographic area, BMI, and baseline HbA1c subgroups. Fewer tolerability events occurred in the VM cohort versus the comparator cohort (8.3% vs. 16.2%, P < 0.001; relative risk = 0.51, 95% CI 0.36–0.72). Conclusion: Compared with dual OAD non-vildagliptin combination therapies, vildagliptin add-on to metformin is effective and safe to achieve glycemic control in Chinese patients with T2DM. Funding: Novartis. [ABSTRACT FROM AUTHOR]

Background: The red cell distribution width (RDW) has been shown to be associated with the incidence and complications of type 2 diabetes (T2D). However, the relevance of RDW with the risk of being in poor glycemic control among patients with established T2D is largely overlooked. Methods: A total of 702 T2D participants from the REACTION study were enrolled in this study. Blood routine index, fasting plasma glucose, hemoglobin A1c and lipid profile data were available for all of the enrolled population. Results: The univariate logistic analysis revealed a significant association between RDW and the risk of being in poor glycemic control among T2D subjects with an odds ratio (OR) and a 95% confidence interval (CI) of 0.5 and 0.3-0.8, respectively, for the fourth vs the first quartile of RDW. The association strengthened after multivariable adjustment (OR [95% CI]: 0.3 [0.2-0.7]). Interaction and stratified analyses indicated that this association was seen only among T2D subjects with lower body mass index and/or serum lipid levels. Conclusion: T2D patients with higher RDW had significantly lower risk of being in poor glycemic control. RDW may contribute to risk assessment for T2D individuals at risk of being in poor glycemic control. [ABSTRACT FROM AUTHOR]

Aim To investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy. Methods SMART was a 24-week, multicentre, randomized, parallel-group, open-label Phase IV study conducted at 35 sites in China ( September 24, 2014 to September 29, 2015). The primary outcome was absolute change from baseline in HbA1c at Week 24. Secondary outcomes assessed at Week 24 included the proportion of patients achieving HbA1c < 7.0%, the proportion of patients with gastrointestinal adverse events ( GI AEs), and the proportion of patients achieving HbA1c < 7.0% without GI AEs. Safety and tolerability were also assessed in all patients who received ≥1 dose of study medication. Results Four-hundred and eighty-eight patients were randomized (1:1) to saxagliptin or acarbose via a central randomization system (interactive voice/web response system); 241 and 244 patients received saxagliptin and acarbose, respectively, and 238 and 243 of these had ≥1 pre- and ≥1 post-baseline efficacy values recorded. Saxagliptin was non-inferior to acarbose for glycaemic control [ Week 24 HbA1c change: −0.82% and −0.78%, respectively; difference (95% confidence interval): −0.04 (−0.22, 0.13)%], with similar proportions of patients in both treatment groups achieving HbA1c < 7.0%. However, fewer GI AEs were reported with saxagliptin compared with acarbose, and a greater number of patients who received saxagliptin achieved HbA1c < 7.0% without GI AEs compared with those receiving acarbose. Conclusion Both therapies had similar efficacy profiles. However, saxagliptin was associated with fewer GI AEs, suggesting it might be preferential for clinical practice. Clinical trial registration number: NCT02243176, . [ABSTRACT FROM AUTHOR]

Aim: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control.Methods: Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2.5mg/metformin 500mg bid; or linagliptin 2.5mg/metformin 1000mg bid. Patients with severe hyperglycemia (HbA1c ⩾11.0% [97mmol/mol]) received linagliptin 2.5mg/metformin 1000mg bid or linagliptin 5mg qd (switched at week 12 from linagliptin to SPC if HbA1c >8.0% [64mmol/mol]). The main group primary endpoint was HbA1c change from baseline to week 24.Results: At week 24, adjusted mean change from baseline in HbA1c (main group, n=733) was: linagliptin 5mg qd, -1.3%; metformin 500mg bid, -1.6%; metformin 1000mg bid, -2.1%; linagliptin 2.5mg/metformin 500mg bid, -2.2%; linagliptin 2.5mg/metformin 1000mg bid, -2.3%. The first test of primary HbA1c analysis (linagliptin 2.5mg/metformin 1000mg bid vs. metformin 1000mg bid) was borderline non-significant; however, SPCs produced significantly greater reductions in HbA1c from baseline versus respective monotherapies in all but one pre-defined sensitivity analysis. In the severe hyperglycemia group (n=143), linagliptin 2.5mg/metformin 1000mg bid produced a superior HbA1c reduction (-4.7%) versus linagliptin 5mg qd (-3.5%) after 12weeks. Hypoglycemic adverse events were low across groups.Conclusions: Initial linagliptin/metformin SPC significantly improved glycemic control in this population. [ABSTRACT FROM AUTHOR]

Backgrounds: As patients attending hospitals of different grades in China may receive different medical care, we investigated the clinical efficacy and safety of routine insulin therapy in patients with type 2 diabetes who were treated at grade 2 and grade 3 (highest grade) hospitals in China.Methods: 2683 patients with type 2 diabetes were enrolled in a multicenter, nonrandomized, open-label, noninterventional, 12-week clinical trial performed at 62 Chinese hospitals. Patients were divided into two groups according to the hospitals' grading. Data were analyzed for efficacy (changes and normalization of glycated hemoglobin [HbA1c] and changes in fasting plasma glucose and 2-h postprandial blood glucose [PBG] levels from baseline to the final visit) and for safety (hypoglycemia).Results: After 12 weeks of routine human insulin (SciLin) therapy, decreases in mean HbA1c and PBG levels were significantly greater in patients treated at second-grade hospitals (all P < 0.001 vs. third-grade hospitals), and the HbA1c success rate (<7%) was significantly higher (46.94% vs. 38.85%; P = 0.0002). However, patients treated at second-grade hospitals had more weight gain (0.29 kg vs. 0.04 kg; P < 0.0001) and a higher incidence of total hypoglycemic events (21.82% vs. 16.79%; P = 0.0002).Conclusions: Routine insulin treatment of patients with type 2 diabetes in China demonstrates acceptable safety and effectiveness, improving blood glucose control with a low incidence of severe hypoglycemia. Patients treated at second-grade hospitals had a greater HbA1c success rate than those treated at third-grade hospitals, but with more weight gain and more hypoglycemic events. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore independent associations between serum uric acid and hypoglycaemia, and whether mildly increased serum uric acid exacerbated the association between mild decline in estimated glomerular filtration rate (eGFR) and hypoglycaemia.Methods: A cross-sectional survey of 6713 inpatients with type 2 diabetes and eGFR ≥60 mL/min/1.73 m2 and admitted to 81 tertiary care hospitals in China was conducted. Self-reported asymptotic hypoglycaemia with plasma glucose ≤3.9 mmol/L, hypoglycaemia episodes with symptoms in 1 month or hypoglycaemia that needed assistance from other people in 3 months before hospitalization was used to define hypoglycaemia. Binary logistic regression was used to estimate odds ratios of serum uric acid for hypoglycaemia. Three measures, that is, relative excess risk due to interaction (RERI), attributable proportion due to interaction and synergy index (S) were used to estimate the effect of mildly decreased eGFR on the association of serum uric acid with hypoglycaemia.Results: Serum uric acid was associated with hypoglycaemia in an ordinal manner (P for trend <0.01) with an odds ratio of top quartile versus the lowest quartile up to 3.03 (95% confidence interval: 2.13-4.32). The odds ratio of serum uric acid levels ≥ versus <283 µmol/L (i.e. the median) was 1.98 (95% confidence interval:1.58-2.48). Serum uric acid levels ≥ versus <283 µmol/L greatly enhanced the association between mild decline in eGFR (eGFR < 90 mL/min/1.73 m2 ) and hypoglycaemia from 0.94 (0.36-2.43) to 3.90 (2.55-5.95), with a significant additive interaction (P < 0.05 for RERI, AP and S).Conclusions: Mildly increased serum uric acid was associated with increased risk of hypoglycaemia and enhanced the association between mildly decreased eGFR and hypoglycaemia in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Insulin resistance, a major characteristic of type 2 diabetes (T2D), is closely associated with adipose tissue macrophages (ATMs) that induce chronic low-grade inflammation. Recently, mesenchymal stem cells (MSCs) have been identified in alleviation of insulin resistance. However, the underlying mechanism still remains elusive. Thus, we aimed to investigate whether the effect of MSCs on insulin resistance was related to macrophages phenotypes in adipose tissues of T2D rats. In this study, human umbilical cord-derived MSCs (UC-MSCs) infusion produced significantly anti-diabetic effects and promoted insulin sensitivity in T2D rats that were induced by a high-fat diet combined with streptozotocin and directed ATMs into an alternatively activated phenotype (M2, anti-inflammatory). In vitro, MSC-induced M2 macrophages alleviated insulin resistance caused by classically activated macrophages (M1, pro-inflammatory). Further analysis showed that M1 stimulated UC-MSCs to increase expression of interleukin (IL)-6, a molecule which upregulated IL4R expression, promoted phosphorylation of STAT6 in macrophages, and eventually polarized macrophages into M2 phenotype. Moreover, the UC-MSCs effect on macrophages was largely abrogated by small interfering RNA (siRNA) knockdown of IL-6. Together, our results indicate that UC-MSCs can alleviate insulin resistance in part via production of IL-6 that elicits M2 polarization. Additionally, human obesity and insulin resistance were associated with increased pro-inflammatory ATMs infiltration. Thus, MSCs may be a new treatment for obesity-related insulin resistance and T2D concerning macrophage polarized effects. S tem C ells 2016;34:627-639 [ABSTRACT FROM AUTHOR]

Objective: To clarify the quantitative relationship of body mass index (BMI) change from early adulthood to midlife with presence of type 2 diabetes mellitus (T2DM) after midlife.Methods: This study included 120,666 middle-aged and elderly, whose retrospectively self-reported body weight at 20 and 40 years and measured height were available. BMI at 20 and 40 years and BMI change in between were defined as early-adulthood BMI, midlife BMI, and early-adulthood BMI change.Results: The odds ratio (OR) for T2DM associated with an 1-unit increment of early-adulthood or midlife BMI was 1.08 (95% confidence interval (CI), 1.07-1.08) and 1.09 (95% CI, 1.09-1.10) respectively. In the cross-tabulation of both early-adulthood BMI and BMI change, the prevalence of T2DM increased across both variables. Compared with participants with normal early-adulthood weight and BMI increase/decrease ≤1, the OR (95% CI) for T2DM of participants with early-adulthood overweight/obesity and BMI increase ≥4 kg/m(2) was 3.49 (3.05-4.00). For participants with early-adulthood underweight and BMI increase/decrease ≤ 1, the OR (95% CI) was 0.85 (0.75-0.97). Subgroup analysis according to sex and age showed similar trends.Conclusions: Early-adulthood BMI may influence T2DM prevalence after midlife independent of current BMI. T2DM prevalence after midlife was positively associated with early-adulthood weight gain and inversely related to early-adulthood weight loss, while early-adulthood weight loss could not completely negate the adverse effect of early-adulthood overweight/obesity on diabetes. [ABSTRACT FROM AUTHOR]

We recruited a group of 6713 consecutive Chinese patients with T2D but normal renal and liver function who were admitted to one of 81 top tertiary care hospitals in China. Mild hypoglycaemia was defined as having symptomatic hypoglycaemia in one month before hospitalization. Severe hypoglycaemia was defined as having hypoglycaemia that needed assistance from other people in three months before hospitalization. Prior cardiovascular disease (CVD) was defined as having coronary heart disease, stroke, or peripheral arterial disease. Of 6713 patients, 80 and 304 had severe and mild hypoglycaemia episodes, respectively, and 561 had CVD. Patients with severe and mild hypoglycaemia episodes were more likely to have prior CVD (32.5% versus 16.5% versus 7.7%, P < 0.0001). Both mild and severe hypoglycaemia were associated with increased risk of CVD (adjusted odds ratios (ORs): 2.64, 95% CI: 1.85-3.76 for mild hypoglycaemia; 6.59, 95% CI: 3.79-11.45 for sever hypoglycaemia) than those patients free of hypoglycaemia. Further adjustment for lipid profile did not change these two ORs. In the same way, the ORs of lipid profile for CVD were similar before and after adjustment for hypoglycaemia. We concluded that hypoglycaemia and lipid profile were independently associated with increased risk of CVD. [ABSTRACT FROM AUTHOR]

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Background: Long-term diabetes-associated complications are the major causes of morbidity and mortality in individuals with diabetes. These diabetic complications are closely linked to immune system activation along with chronic, non-resolving inflammation, but therapies to directly reverse these complications are still not available. Our previous study demonstrated that mesenchymal stem cells (MSCs) attenuated chronic inflammation in type 2 diabetes mellitus (T2DM), resulting in improved insulin sensitivity and islet function. Therefore, we speculated that MSCs might exert anti-inflammatory effects and promote the reversal of diabetes-induced kidney, liver, lung, heart, and lens diseases in T2DM rats. Methods: We induced a long-term T2DM complication rat model by using a combination of a low dose of streptozotocin (STZ) with a high-fat diet (HFD) for 32 weeks. Adipose-derived mesenchymal stem cells (ADSCs) were systemically administered once a week for 24 weeks. Then, we investigated the role of ADSCs in modulating the progress of long-term diabetic complications. Results: Multiple infusions of ADSCs attenuated chronic kidney disease (CKD), nonalcoholic steatohepatitis (NASH), lung fibrosis, and cataracts; improved cardiac function; and lowered serum lipid levels in T2DM rats. Moreover, the levels of inflammatory cytokines in the serum of each animal group revealed that ADSC infusions were able to not only inhibit pro-inflammatory cytokines IL-6, IL-1β, and TNF-α expression but also increase anti-inflammatory cytokine IL-10 systematically. Additionally, MSCs reduced the number of iNOS(+) M1 macrophages and restored the number of CD163(+) M2 macrophages. Conclusions: Multiple intravenous infusions of ADSCs produced significant protective effects against long-term T2DM complications by alleviating inflammation and promoting tissue repair. The present study suggests ADSCs may be a novel, alternative cell therapy for long-term diabetic complications. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have emerged as a promising therapy for type 2 diabetes (T2D). Mechanistic researches demonstrate that the anti-diabetic effect of MSCs is partially mediated by eliciting macrophages into an anti-inflammatory phenotype thus alleviating insulin resistance. However, single MSC infusion is insufficient to ameliorate sustained hyperglycemia or normalize blood glucose levels. In this study, we used decitabine (DAC), which is involved in the regulation of macrophage polarization, to test whether MSCs combined with decitabine can prolong and enhance the anti-diabetic effect in T2D mice. Methods: High-fat diet (HFD) and streptozocin (STZ) were given to induce T2D mouse model. Successfully induced T2D mice were randomly divided into four groups: T2D group, MSC group, DAC group, and MSC + DAC group. Blood glucose was monitored, and glucose tolerance and insulin sensitivity were evaluated during the entire analysis period. Epididymal fat was extracted for analysis of macrophage phenotype and inflammation in adipose tissue. In vitro, we examined the effect of MSC + DAC on macrophage polarization in bone marrow-derived macrophages (BMDMs) and explore the possible mechanism. Results: MSC infusion effectively improved insulin sensitivity and glucose homeostasis in T2D mice within 1 week, whereas combination therapy of MSCs + DAC extended the anti-diabetic effects of MSCs from 1 to 4 weeks (the end of the observation). Correspondingly, more M2 macrophages in adipose tissue were observed in the combination therapy group over the entire study period. In vitro, compared with the MSC group, MSCs combined with decitabine more effectively polarized M1 macrophages to M2 macrophages. Further analysis showed that the effect of MSC + DAC on macrophage polarization was largely abrogated by the peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662. Conclusions: Our data suggest that MSCs combined with decitabine can more effectively alleviate insulin resistance and prolong and enhance the anti-diabetic effect of MSCs in T2D mice in part by prompting M2 polarization in a PPARγ-dependent manner. Thus, decitabine may be an applicable addition to MSCs for diabetes therapy. UC-MSCs combined with decitabine activate the IL4R/STAT6/STAT3/PPARγ axis to further promote M2 macrophage polarization in adipose tissue, reduce inflammation, improve insulin sensitivity, and lead to better glucose metabolism and long-term hypoglycemic effects [ABSTRACT FROM AUTHOR]

Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion. [ABSTRACT FROM AUTHOR]

The authors aimed to observe β-cell dedifferentiation in type 2 diabetes mellitus (T2DM) and investigate the reversal effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on early- and late-stage β-cell dedifferentiation. In high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mice, the authors examined the predominant role of β-cell dedifferentiation over apoptosis in the development of T2DM and observed the reversion of β-cell dedifferentiation by UC-MSCs. Next, the authors used db/db mice to observe the progress of β-cell dedifferentiation from early to late stage, after which UC-MSC infusions of the same amount were performed in the early and late stages of dedifferentiation. Improvement in metabolic indices and restoration of β-cell dedifferentiation markers were examined. In HFD/STZ-induced T2DM mice, the proportion of β-cell dedifferentiation was much greater than that of apoptosis, demonstrating that β-cell dedifferentiation was the predominant contributor to T2DM. UC-MSC infusions significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In db/db mice, UC-MSC infusions in the early stage significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In the late stage, UC-MSC infusions mildly improved glucose homeostasis and partially reversed β-cell dedifferentiation. Combining with other studies, the authors found that the reversal effect of UC-MSCs on β-cell dedifferentiation relied on the simultaneous relief of glucose and lipid metabolic disorders. UC-MSC therapy is a promising strategy for reversing β-cell dedifferentiation in T2DM, and the reversal effect is greater in the early stage than in the late stage of β-cell dedifferentiation. [ABSTRACT FROM AUTHOR]

Aims The present study aimed to examine the nonlinear associations between risk factors and mild hypoglycemia in Chinese patients with type 2 diabetes mellitus (T2DM). Methods From May 2013 to August 2013, we conducted a cross sectional survey of 6633 inpatients with T2DM and without severe hypoglycemia, aged 21–77 years, from 81 top tertiary hospitals in China. Mild hypoglycemia was defined as having hypoglycemia with symptoms in one month. Binary logistic regression analysis with restricted cubic splines was used to estimate odds ratio curves of non-linear risk factors for mild hypoglycemia. Results Increasing body mass index was associated with decreasing risk of mild hypoglycemia in a linear manner while age, duration of diabetes, glycated hemoglobin (HbA1 c ), mean artery pressure and lipids were associated with mild hypoglycemia in non-linear manners. Age ≥ 40 years, duration ≥ 2 years, HbA1 c ≥ 7.0–<11.5% (≥ 53–<102 mmol/mol), triglyceride ≥ 1.7–<3.6 mmol/L, low-density lipoprotein cholesterol (LDL-C) ≥ 2.6–<4.8 mmol/L, and high-density lipoprotein cholesterol (HDL-C) ≥ 1.2–<4.8 mmol/L were associated with increased risks of mild hypoglycemia. Conclusions Chinese T2DM patients with age ≥ 40 years, duration of diabetes ≥ 2–<6 years, HbA1 c ≥ 7.0–<11.5% (≥ 53–<102 mmol/mol), LDL-C ≥ 2.6–<4.8 mmol/L, HDL-C ≥ 1.2–<4.8 mmol/L or triglyceride ≥ 1.7–<3.6 mmol/L were at particularly high risk for mild hypoglycemia. [ABSTRACT FROM AUTHOR]

Highlights: [•] Multiple MSC infusions could reverse hyperglycemia in T2D rats. [•] Multiple MSC infusions could restore the injured pancreatic islets in T2D rats. [•] The effect of multiple-MSC infusions was strong at early-phase. [•] Cytokines of MSCs are responsible for the anti-diabetes effects. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to assess the effects of the hemoglobin glycation index (HGI) on hyperglycemia diagnosis and summarize the general characteristics of patients with a high-HGI phenotype.Methods: The fasting plasma glucose and glycated hemoglobin (HbA1c) levels of participants (n=47,648) were used to estimate a linear regression equation and determine the baseline HGI. Overall, 42,317 participants without a history of diabetes were included in the final analysis. The participants were divided into three groups according to the tertiles (low, moderate, and high) of baseline HGI. Proportions and variables were compared among the three HGI groups. A multivariate ordered logistic regression model was used to explore associations between related variables and the high-HGI phenotype.Results: Regression analysis indicated that the high-HGI phenotype was positively associated with female sex, advanced age, obesity, increased low-density lipoprotein and triglyceride levels, decreased high-density lipoprotein cholesterol, and postprandial glycemic excursion levels (all P<0.05). The prevalence of hyperglycemia increased from the low- to the high-HGI groups when using HbA1c for diagnosis.Conclusions: Individuals with high HGI have similar clinical characteristics. Measuring HbA1c alone for diagnosis could lead to inappropriate diabetes management decisions in people with low or high HGI. [ABSTRACT FROM AUTHOR]

Abstract: Background: Individually, diabetes mellitus, hypertension, and dyslipidemia have been shown to increase the risk of cardiovascular disease. While traditional management of Type 2 diabetes has focused mainly on glycemic control, robust evidence supports the integration of hypertension and dyslipidemia management to reduce the risk of cardiovascular disease. The primary objective of this study was to assess the level of control of blood glucose, blood pressure, and blood lipids (3Bs) among patients with type 2 diabetes. An additional objective was to investigate the impact of hospital type, physician specialty, treatment pattern, and patient profile on clinical outcomes. Methods: This was a cross-sectional, multicenter observational study. A nationally representative sample of outpatients with established type 2 diabetes were enrolled at hospitals representative of geographic regions, tiers, and physician specialties in China. Main clinical measurements were the levels of glycosylated hemoglobin (HbA1c), blood pressure, and total serum cholesterol in reference to target goals. Results: A total of 25,817 adults with type 2 diabetes (mean age 62.6 years, 47% male) were enrolled at 104 hospitals. Seventy-two percent reported comorbid hypertension, dyslipidemia, or both. Patients with concurrent type 2 diabetes, hypertension, and dyslipidemia were 6 times more likely to report a prior history of cardiovascular disease compared with those with type 2 diabetes alone. The mean HbA1c level was 7.6%. While 47.7%, 28.4%, and 36.1% of patients achieved the individual target goals for control of blood glucose (HbA1c <7%), blood pressure (systolic blood pressure <130 mm Hg, diastolic blood pressure <80 mm Hg), and blood lipids (total cholesterol <4.5 mmol/L), respectively, only 5.6% achieved all 3 target goals. Lower body mass index (<24 kg/m2), no active smoking or drinking, higher education, and diabetes duration <5 years were independent predictors of better cardiovascular disease risk control. Conclusion: Achieving adequate control of risk factors for cardiovascular disease in patients with type 2 diabetes remains a clinical challenge. Interventions to achieve control of 3Bs coupled with modification of additional cardiovascular disease predictors are crucial for optimization of clinical outcomes in patients with type 2 diabetes. [Copyright &y& Elsevier]