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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)-AGE age (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-AGE age 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-AGE age 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-AGE age and ELC., Conclusion: ELC is associated with coronary heart disease, and the SAF-AGE has a potential role in ELC development in elder people., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Gitelman Syndrome (GS) patients frequently exhibit disrupted glucose metabolism, attributed to hypokalemia, hypomagnesemia and heightened aldosterone. This study delved into the genetic underpinnings linked to insulin resistance and diabetes in a GS patient, contextualized within his family history., Methods: The hydrochlorothiazide and furosemide loading test were performed to ascertain the presence of GS. Oral glucose tolerance test (OGTT) evaluated glucose metabolism and insulin sensitivity. Whole-exome sequencing, validated by Sanger sequencing, was employed to confirm gene mutations, which were then tracked among the patient's relatives., Results: Symptoms and laboratory examination confirmed the clinical diagnosis of GS. Comprehensive whole-exome sequencing, augmented by Sanger sequencing validation, revealed a compound heterozygous mutation within the SLC12A3 gene (c.1108G>C in exon 9, c.676G>A in exon 5 and c.2398G>A in exon 20) in the patient. The OGTT affirmed diabetes and heightened insulin resistance, distinct from previous patients with GS we evaluated. Further genetic analysis identified a missense heterozygous mutation (c.97C>G in exon 1) within the PDX1 gene, inherited from the patient's diabetic mother without GS. Furthermore, the patient's brother, with impaired glucose tolerance but regular potassium levels, also bore this mutation, hinting at additional impacts of the PDX1 gene mutation on glucose metabolism regulation beyond the known impacts of GS., Conclusion: This study unveils unprecedented compound heterozygous mutations in the SLC12A3 and PDX1 genes in a GS patient. These findings illuminate the potential complex genetic factors influencing glucose metabolism disruptions in GS., Take-Home Message: This research uncovers a novel combination of SLC12A3 and PDX1 gene mutations in a Gitelman Syndrome patient, revealing intricate genetic factors that potentially disrupt glucose metabolism and shedding light on familial diabetes links., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yin, Li, Yu, Xin, Zhu, Hu, Chen, Gu, Mu, Zang and Lyu.)

Aim: Millions of people are afflicted by depression, a highly prevalent mental illness with increased morbidity and mortality. Advanced glycation end-products (AGEs) are potential risk factors for depression. We aimed to investigate the correlation of AGEs with depressive symptoms and the severity of depressive symptoms., Methods: This study was nested in the prospective REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study and included 4420 eligible participants. skin autofluorescence (SAF) was used to measure skin AGEs. Depressive symptoms were evaluated by the Self-Rating Depression Scale (SDS). Multiple logistic regression analysis was used to assess the association of AGEs with depressive symptoms and the severity of depressive symptoms., Results: Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGEs and the risk of depressive symptoms with the OR [95% confidence interval (CI), p value] of 1.24 (95% CI: 1.03-1.50, p = 0.022), 1.39 (95% CI: 1.15-1.68, p = 0.001) and 1.57 (95% CI: 1.28-1.91, p < 0.001) for multivariable-adjusted model respectively. And SAF-AGEs were associated with the severity of depressive symptoms with the multivariable-adjusted OR (95% CI, p value) of 1.06 (95% CI:0.79-1.43, p = 0.681), 1.47 (95% CI: 1.08-1.99, p = 0.014), and 1.54 (95% CI: 1.12-2.11, p = 0.008) respectively. Stratified analyses showed that SAF-AGEs were significantly associated with the severity of depressive symptoms only in females, overweight people, individuals with hypertension, and those without diabetes and insomnia., Conclusions: The present study showed that a higher SAF-AGEs level was associated with depressive symptoms and the severity of depressive symptoms., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Spouses share common socioeconomic, environmental, and lifestyle factors, and multiple studies have found that spousal diabetes status was associated with diabetes prevalence. But the association of spousal diabetes status and ideal cardiovascular health metrics (ICVHMs) assessed by the American Heart Association's Life's Essential 8 measures with incident diabetes has not been comprehensively characterized, especially in large-scale cohort studies., Objective: To explore the association of spousal diabetes status and cardiovascular health metrics with risk of incident diabetes in Chinese adults., Design, Setting, and Participants: This cohort study included individuals in the China Cardiovascular Disease and Cancer Cohort without diabetes who underwent baseline and follow-up glucose measurements and had spouses with baseline glucose measurements. The data were collected in January 2011 to December 2012 and March 2014 to December 2016. The spousal study had a mean (SD) follow-up of 3.6 (0.9) years (median [IQR], 3.2 [2.9-4.5] years). Statistical analysis was performed from July to November 2022., Exposure: Spousal diabetes status was diagnosed according to the 2010 American Diabetes Association (ADA) criteria. All participants provided detailed clinical, sociodemographic, and lifestyle information included in cardiovascular health metrics., Main Outcomes and Measures: Incident diabetes, diagnosed according to 2010 ADA criteria., Results: Overall, 34 821 individuals were included, with a mean (SD) age of 56.4 (8.3) years and 16 699 (48.0%) male participants. Spousal diabetes diagnosis was associated with an increased risk of incident diabetes (hazard ratio [HR], 1.15; 95% CI, 1.03-1.30). Furthermore, participants whose spouses had uncontrolled glycated hemoglobin (HbA1c) had a higher risk of diabetes (HR, 1.20; 95% CI, 1.04-1.39) but the risk of diabetes in participants whose spouses had controlled HbA1c did not increase significantly (HR, 1.10; 95% CI, 0.92-1.30). Moreover, this association varied with composite cardiovascular health status. Diabetes risk in individuals who had poor cardiovascular health status (<4 ICVHMs) was associated with spousal diabetes status (3 ICVHMs: HR, 1.50; 95% CI, 1.15-1.97), while diabetes risk in individuals who had intermediate to ideal cardiovascular health status (≥4 ICVHMs) was not associated with it (4 ICVHMs: HR, 1.01; 95% CI, 0.69-1.50)., Conclusions and Relevance: In this study, spousal diabetes diagnosis with uncontrolled HbA1c level was associated with increased risk of incident diabetes, but strict management of spousal HbA1c level and improving ICVHM profiles may attenuate the association of spousal diabetes status with diabetes risk. These findings suggest the potential benefit of couple-based lifestyle or pharmaceutical interventions for diabetes.

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic β cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: The association between remnant cholesterol (RC) and diabetes remains unclear because of limited study and data. This study attempted to explore the association between RC and diabetes in a large sample, multicenter general population., Methods: The current study included 36 684 participants from eight provinces across China. Subjects were quartered according to the RC quartile. Logistic regression analysis was used to evaluate the association between RC and diabetes., Results: After adjusting for potential confounding factors, RC was still significantly associated with diabetes (Q4: odds ratio [OR]:1.147, 95% confidence interval [CI]: 1.049-1.254, p = .003). In addition, RC and diabetes were still significantly associated when triglycerides (TG) were <1.7 mmol/L (Q4: OR: 1.155, 95% CI: 1.005-1.327, p = .042), low-density lipoprotein cholesterol (LDL-C) <3.4 mmol/L (Q4: OR: 1.130, 95% CI: 1.011-1.264, p = .032), or HDL-C (high-density lipoprotein cholesterol) ≥1.0 mmol/L (Q4: OR: 1.116, 95% CI: 1.007-1.237, p = .037). In the stratification analysis, elevated RC was significantly associated with diabetes in subjects with systolic blood pressure (SBP) <140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg, 60 ≤ estimated glomerular filtration rate (eGFR) ≤90 ml/min per 1.73 m 2 , younger than 55 years old and female., Conclusion: In the Chinese community, RC is significantly correlated with diabetes, even when TG, LDL-C, or HDL-C were controlled within the appropriate range recommended by the guidelines., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: The association between the Chinese Visceral Adiposity Index (CVAI) and urinary albumin to creatinine ratio (UACR) has not been illustrated. The current study aimed to investigate the association between CVAI and UACR and to compare the discriminative power of CVAI, triglyceride, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with UACR in the Chinese community population., Methods: This study included 34 732 participants from the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. Binary logistic regression analyses were performed to detect the association between CVAI, triglyceride, BMI, WC, WHR and UACR., Results: Binary logistic regression analysis showed that, after adjusting for potential confounders, in women, CVAI (odds ratio [OR]:1.16, 95% confidence interval [CI]: 1.01-1.34) and triglyceride (OR: 1.18, 95% CI: 1.04-1.33) were associated with UACR, whereas BMI, WC, and WHR were not associated with UACR; in men, CVAI (OR: 1.24, 95% CI: 1.02-1.50), WC (OR: 1.21, 95% CI 1.00-1.48), and triglycerides (OR: 1.18, 95% CI 0.97-1.44) were associated with UACR, whereas BMI and WHR were not associated with UACR. Stratified analysis showed that the correlation between CVAI and UACR was stronger in the population with 5.6 ≤ fasting blood glucose (FBG) <7.0 or 7.8 ≤ post-load blood glucose (PBG) <11.1 mmol/L, FBG ≥7.0 or PBG ≥11.1, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg., Conclusions: In the Chinese general population, CVAI and UACR were significantly associated in both genders. At higher CVAI levels, the population with prediabetes, diabetes, and hypertension has a more significant association between CVAI and UACR., (© 2022 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them., Methods: Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self-report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator., Results: Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12-1.27), while college-educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73-0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (β[SE] 0.0387 [0.0037]) and negative in women (β[SE] -0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women., Conclusions: In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women., (© 2022 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status., Research Design and Methods: We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality., Results: In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82-1.30), 1.23 (1.07-1.42), and 1.61 (1.30-2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92-1.18), 1.12 (1.06-1.18), and 1.15 (1.09-1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2-34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15-17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44-77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters., Conclusions: Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity., (© 2022 by the American Diabetes Association.)

Background: To identify novel clinical phenotypic signatures of congenital nephrogenic diabetes insipidus (CNDI)., Methods: A Chinese family with CNDI was recruited for participation in this study. The proband and one of his uncles suffered from polydipsia and polyuria since infancy. The results of clinical testing indicated the diagnosis of CNDI. 10 family members had similar symptoms but did not seek medical advice. Genetic testing of mutations in the coding region of the aquaporin 2 ( AQP2 ) gene and the arginine vasopressin receptor 2 ( AVPR2 ) gene were carried out in 11 family members. Somatic DNA from 5 female family members was used to test for methylation of polymorphic CAG repeats in the human androgen receptor (AR) gene, as an index for X-chromosome inactivation pattern (XCIP)., Results: AQP2 gene mutations were not found in any family members, but a novel missense mutation (814th base A>G) in exon 2 of the AVPR2 gene was identified in 10 individuals. This mutation leads to a Met 272 Val (GAT-GGT) amino acid substitution. Skewed X-chromosome inactivation patterns of the normal X allele were observed in 4 females with the AVPR2 gene mutation and symptoms of diabetes insipidus, but not in an asymptomatic female with the AVPR2 gene mutation., Conclusions: Met 272 Val mutation of the AVPR2 gene was identified as a novel genetic risk factor for CDNI. The clinical NDI phenotype of female carriers with heterozygous AVPR2 mutation may be caused by X-chromosome inactivation induced by dominant methylation of the normal allele of AVPR2 gene., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Li Zang et al.)

Background: Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD., Methods: This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011-2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline., Results: Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17-1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01-1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71-1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77-2.14) or former smokers (HR, 1.22; 95% CI, 0.66-2.28)., Conclusions: Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking., (© 2022. The Author(s).)

Context: Diabetes, hypertension and dyslipidemia accelerates the incidence of cardiovascular disease (CVD) events. However, data regarding the association between main cardiometabolic morbidities such as diabetes, hypertension, and dyslipidemia and the subsequent risk of CVD events in Chinese adults are still limited., Objective: To investigate the associations between individual and combined cardiometabolic morbidities and incident cardiovascular events in Chinese adults., Methods: Baseline data were obtained from a prospective, nationwide, and population-based cohort study in China during 2011-2012. A total of 133 572 participants aged ≥40 years were included in the study. The main outcome measures were CVD events., Results: Compared with participants without diabetes, hypertension and dyslipidemia, participants with only diabetes (hazard ratio [HR], 1.58; 95% CI, 1.32-1.90) or only hypertension (2.04; 1.82-2.28) exhibited significantly higher risk for CVD events, while participants with only dyslipidemia (0.97; 0.84-1.12) exhibited no significantly higher risk for CVD events. When analyzed collectively, participants with diabetes plus hypertension (HR, 2.67; 95% CI, 2.33-3.06), diabetes plus dyslipidemia (1.57; 1.32-1.87), and hypertension plus dyslipidemia (2.12; 1.88-2.39) exhibited significantly higher risk for CVD. Moreover, participants with the combination of diabetes, hypertension, and dyslipidemia exhibited the highest risk for CVD events (HR, 3.06; 95% CI, 2.71-3.46). Multivariable-adjusted HRs (95% CIs) for CVD associated with diabetes based on fasting glucose ≥7.0 mmol/L, oral glucose tolerance test 2-hour glucose ≥11.1 mmol/L, and hemoglobin A1c ≥6.5% were 1.64 (1.51-1.78), 1.57 (1.45-1.69), and 1.54 (1.42-1.66), respectively; associated with hypertension based on systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were 1.89 (1.76-2.03) and 1.74 (1.60-1.88), respectively; associated with dyslipidemia based on total cholesterol ≥6.22 mmol/L, low-density lipoprotein cholesterol ≥4.14 mmol/L, high-density lipoprotein cholesterol <1.04 mmol/L, and triglycerides ≥2.26 mmol/L were 1.18 (1.08-1.30), 1.30 (1.17-1.44), 1.00 (0.92-1.09), and 1.10 (1.01-1.20), respectively., Conclusion: Diabetes, hypertension and dyslipidemia showed additive associations with the risk of CVD events in middle-aged and elderly Chinese adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: National investigations of age-specific modifiable risk profiles for diabetes are crucial to promote personalised strategies for the prevention and control of diabetes, particularly in countries such as China, which is experiencing both a diabetes epidemic and a rapidly ageing population. We aimed to examine the associations of 12 potentially modifiable socioeconomic, lifestyle, and metabolic risk factors with diabetes in a nationwide prospective cohort of Chinese adults across four age groups., Methods: We analysed data from the China Cardiometabolic Disease and Cancer Cohort Study, a nationwide, population-based, cohort study done between Jan 1, 2011, and Dec 31, 2016. Among 93 781 participants without diabetes at baseline and with complete information available about risk factors and diabetes incidence, we examined the hazard ratios (HRs) and population-attributable risk percentages (PAR%s) of incident diabetes associated with 12 potentially modifiable risk factors: two socioeconomic risk factors (less education and intermediate or low grade occupation), five lifestyle risk factors (unhealthy diet, physical inactivity, current alcohol consumption, current smoking, and unhealthy sleep), and five metabolic risk factors (general or central obesity, insulin resistance, prediabetes, hypertension, and dyslipidaemia) across four age groups (40 to <55 years, 55 to <65 years, 65 to <75 years, and ≥75 years)., Findings: With 337 932 person-years' follow-up, 6171 participants developed diabetes. Although diabetes risk attributable to metabolic risk factors decreased slightly with age, metabolic risk factors accounted for most incident diabetes cases across all age groups (from a PAR% of 73·8% in participants aged 40 to <55 years to 65·5% in those aged ≥75 years), with prediabetes (ranging from a PAR% of 56·6% to 47·4%, with increasing age) and hypertension (PAR% of 16·8% to 28·6% with increasing age) being the leading risk factors across all age groups. By contrast, diabetes risk attributable to lifestyle risk factors increased substantially with age (with a PAR% of 9·9% in adults aged 40 to <55 years increasing to 29·7% in adults aged ≥75 years), and was especially evident in participants aged 75 years or older, in whom unhealthy sleep was the largest lifestyle factor, accounting for a PAR% of 17·0%. The impact of socioeconomic risk factors on diabetes was mainly driven by less education, which contributed to a PAR% of 7·1% to 12·4% in participants younger than 75 years but conferred no excess risk in participants aged 75 years or older. The risk of diabetes associated with unhealthy sleep significantly increased with age group (HR 1·04 [95% CI 0·95-1·13] among participants aged 40 to <55 years vs 1·36 [1·01-1·85] among participants aged ≥75 years; p interaction =0·0054), but there was an age-related decrease in the risk of diabetes associated with obesity (1·35 [1·23-1·48] vs 0·99 [0·72-1·36]; p interaction =0·0003), prediabetes (3·00 [2·67-3·37] vs 2·18 [1·41-3·37]; p interaction =0·0014), and dyslipidaemia (1·23 [1·13-1·34] vs 0·90 [0·66-1·21]; p interaction =0·016)., Interpretation: These findings provide novel insights into age-related modifiable risk factor profiles for diabetes in Chinese adults, highlighting the importance of prioritising risk factors according to age groups for effective prevention and management of diabetes., Funding: National Natural Science Foundation of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyze association between different perioperative glycemic control strategies and postoperative outcomes in patients with diabetes undergoing cardiac surgery., Methods: MEDLINE, Cochrane Library, Web of Science, EMBASE, Wanfang Data, China National Knowledge Infrastructure (CNKI) and China Biology Medicine (CBM) databases were searched from inception to January 31, 2019. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias of included studies, and consensus was reached by discussion with a third researcher., Results: Six RCTs were included in the meta-analysis. We analyzed the effect of liberal (>180 mg/dl or 10.0 mmol/L), moderate (140-180 mg/dl or 7.8-10.0 mmol/L) and strict (<140 mg/dl or 7.8 mmol/L) glycemic control strategies in patients with diabetes undergoing cardiac surgery. The pooled results showed that strict glycemic control strategy was associated with a significant reduction in the risk of atrial fibrillation [OR = 0.48, 95%CI (0.32, 0.72), P < 0.001] and sternal wound infection [OR = 0.28, 95%CI (0.14, 0.54), P < 0.001], while there was no significant differences in postoperative mortality, stroke, and hypoglycemic episodes when compared with moderate control. In addition, there is no significant difference between moderate and liberal glycemic control strategies in postoperative mortality. However, moderate control was beneficial in reducing atrial fibrillation [OR = 0.28, 95%CI (0.13, 0.60), P = 0.001] compared with the liberal glycemic control strategy., Conclusions: This meta-analysis showed when compared with moderate glycemic control strategy in patients with diabetes undergoing cardiac surgery, maintained strict glycemic control was associated with lower risk of atrial fibrillation and sternal wound infection. No benefit was found with liberal glycemic control strategy, so it could be a poor glycemic control strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Jin, Wang, Ma, Li, An, Wang, Mao, Mu, Chen and Chen.)

Objective: We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk., Research Design and Methods: This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963-1974), fetal exposed (1959-1962), and childhood exposed (1949-1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes., Results: During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05-1.31) and 1.12 (0.96-1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m 2 , or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata ( P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes ( P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24-2.04]), but not in those with two or more ICVHMs., Conclusions: The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs., (© 2020 by the American Diabetes Association.)

Objective: We aimed to determine the individual and combined associations of lifestyle and metabolic factors with new-onset diabetes and major cardiovascular events among a Chinese population aged ≥40 years., Research Design and Methods: Baseline lifestyle information, waist circumference, blood pressure, lipid profiles, and glycemic status were obtained in a nationwide, multicenter, prospective study of 170,240 participants. During the up to 5 years of follow-up, we detected 7,847 individuals with new-onset diabetes according to the American Diabetes Association 2010 criteria and 3,520 cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure., Results: On the basis of 36.13% (population-attributable fraction [PAF]) risk attributed to metabolic risk components collectively, physical inactivity (8.59%), sedentary behavior (6.35%), and unhealthy diet (4.47%) moderately contributed to incident diabetes. Physical inactivity (13.34%), unhealthy diet (8.70%), and current smoking (3.38%) significantly contributed to the risk of major cardiovascular events, on the basis of 37.42% PAF attributed to a cluster of metabolic risk factors. Significant associations of lifestyle health status with diabetes and cardiovascular events were found across all metabolic health categories. Risks of new-onset diabetes and major cardiovascular events increased simultaneously according to the worsening of lifestyle and metabolic health status., Conclusions: We showed robust effects of lifestyle status on new-onset diabetes and major cardiovascular events regardless of metabolic status and a graded increment of risk according to the combination of lifestyle and metabolic health, highlighting the importance of lifestyle modification regardless of the present metabolic status., (© 2020 by the American Diabetes Association.)

Cellular senescence is a fundamental aging mechanism leading to tissue dysfunction. Accumulation of senescent cells is observed in the context of diabetes, which plays an important role in the pathogenesis of diabetes and its complications. Macrophages, the most prevalent leucocytes found in diabetic kidney, have been implicated in the modulation of cellular senescence; however, their role and mechanism in cellular senescence of diabetic kidney have not been determined. In this study, we found trends of cellular senescence in the glomeruli of streptozotocin-induced diabetic mice. The onset of glomerular senescence was confirmed by increased SA-β-gal staining, the upregulation of p16INK4a, p21, and p53 protein levels and the increased expression of SASP RNA. The senescent cells in the glomeruli were mainly endothelial cells. We next confirmed that M1 macrophages accumulated in the glomeruli, occurred just shortly before glomerular senescence. Therefore, we examined whether M1 macrophage accumulation is associated with glomerular endothelial cell senescence. Thus, an in vitro co-culture model was established using human renal glomerular endothelial cells (HRGECs) and M1-polarized THP-1 macrophages. Indeed, M1 macrophages induced senescence in HRGECs. Furthermore, intracellular ROS levels and p38 MAPK signalling activation were significantly increased in HRGECs and reducing ROS generation significantly abolished M1 macrophage-mediated endothelial senescence and p38 MAPK activation, suggesting that M1 macrophage-mediated endothelial senescence is largely dependent on ROS. Thus, our results demonstrate that kidney M1 macrophage accumulation is in connection with endothelial cell senescence and strategy to modulate M1 macrophages accumulation is promising to be a new target for immunotherapy for diabetic kidney disease and other age-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Using the AMSTAR tool, this study evaluated the quality of systematic reviews (SRs) that assessed the efficacy of bariatric surgery in diabetic patients. We aimed to identify studies that can be used as clinical references., Methods: Medline (via PubMed), EMBASE, Epistemonikos, Web of Science, Cochrane Library, CBM, CNKI, and Wanfang Data were systematically searched from inception to December 31, 2017. Two reviewers independently selected SRs and extracted data. Disagreements were solved by discussions or through consultation with a third reviewer. Reviewers extracted data (characteristics of included SRs, e.g., publication year, language, and number of authors) into the predefined tables in the Microsoft Excel 2013 sheet. Data were visualized using the forest plot in RevMan 5.3 software., Results: A total of 64 SRs were included. The average AMSTAR score was 7.4 ± 1.7. AMSTAR scores of 7 ( n = 21, 32.8%) and 8 ( n = 14, 28.1%) were most common. The AMSTAR scores of SRs published before 2016 ( n = 46, 71.9%) were compared with SRs published after 2016 ( n = 18, 28.1%), and no significant differences were observed (MD = -0.79, 95% confidence interval (CI) -1.65-0.07, P = 0.07). For SRs published in Chinese ( n = 17, 26.6%) compared to those published in English ( n = 47, 73.4%), the AMSTAR scores significantly differed (MD = 0.21, 95% CI (-0.55, 0.97), P = 0.59). For SRs published in China ( n = 33, 51.6%) compared to those published outside of China ( n = 31, 48.4%), significant differences in the AMSTAR scores were observed (MD = 1.10, 95% CI (0.29, 1.91), P = 0.008). For SRs with an author number ≤ 6 ( n = 31, 48.4%) compared to SRs with authors ≥ 6 ( n = 33, 51.6%), no significant differences were observed (MD = -0.36, 95% CI (-1.22, 0.50), P = 0.41). For high-quality SRs published after 2016 ( n = 11, 17.2%) compared to other SRs ( n = 53, 82.8%), statistically significant differences were noted (MD = 1.75, 95% CI (1.01, 2.49), P < 0.00001)., Conclusions: The number of SRs assessing the efficacy of bariatric surgery in diabetic patients is increasing by year, but only a small number meet the criteria to support guideline recommendations. Study protocols not being registered, grey literature not retrieved, incorporation of grey literature as exclusion criteria, and failure to evaluate publication bias and report a conflict of interest were the main causes of low AMSTAR scores., Competing Interests: The authors declare no conflict of interests., (Copyright © 2019 Xinye Jin et al.)

Importance: Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear., Objective: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation., Design, Setting, and Participants: The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016., Exposures: Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations., Main Outcomes and Measures: The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure., Results: Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHMs and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58; 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes., Conclusions and Relevance: Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.

Objective: Uncertainty remains regarding the predictive value of various glycemic measures as they relate to the risk of diabetes and its complications. Using the cutoffs recommended by the American Diabetes Association's 2010 criteria, we determined the associations of fasting plasma glucose (FPG), 2-h postload glucose (2h-PG), and HbA 1c with the outcomes., Research Design and Methods: Baseline medical history, FPG, 2h-PG, and HbA 1c were obtained from a population-based cohort of 193,846 adults aged ≥40 years in China during 2011-2012. A follow-up visit was conducted during 2014-2016 in order to assess incident diabetes, cardiovascular disease (CVD), cancer, and mortality., Results: We documented 8,063 cases of diabetes, 3,014 CVD-related events, 1,624 cases of cancer, and 2,409 deaths during up to 5 years of follow-up. Multivariable-adjusted risk ratios (95% CIs) of diabetes associated with prediabetes based on FPG of 100-125 mg/dL, 2h-PG of 140-199 mg/dL, or HbA 1c of 5.7-6.4% (39-47 mmol/mol) were 1.60 (1.43-1.79), 2.72 (2.43-3.04), and 1.49 (1.36-1.62), respectively. Restricted cubic spline analyses suggested J-shaped associations of FPG, 2h-PG, and HbA 1c levels with CVD, cancer, and mortality. Multivariable-adjusted hazard ratios (95% CIs) associated with untreated diabetes based on FPG ≥126 mg/dL, 2h-PG ≥200 mg/dL, or HbA 1c ≥6.5% (48 mmol/mol) were 1.18 (1.05-1.33), 1.31 (1.18-1.45), and 1.20 (1.07-1.34) for CVD; 1.10 (0.92-1.32), 1.44 (1.25-1.67), and 1.08 (0.92-1.28) for cancer; and 1.37 (1.20-1.57), 1.57 (1.41-1.76), and 1.33 (1.17-1.52) for mortality, respectively. 2h-PG remained significantly associated with outcomes in models including FPG and HbA 1c as spline terms. Furthermore, 2h-PG significantly improved the ability of the C statistic to predict diabetes, CVD, and mortality., Conclusions: 2h-PG remains independently predictive of outcomes in models including FPG and HbA 1c . Therefore, in addition to FPG and HbA 1c , routine testing of 2h-PG should be considered in order to better assess the risks of outcomes., (© 2019 by the American Diabetes Association.)

Factors that may result in the occurrence of adverse clinical events in diabetic patients during the postoperative period are not entirely clear. This study evaluated factors that may cause adverse events following elective orthopedic or general surgery.Patients with diabetes who underwent orthopedic or general surgery between January 2010 and October 2015 were retrospectively selected from the General Hospital of People's Liberation Army database. Factors associated with postoperative adverse events were analyzed using multivariable logistic regression.Among 1525 patients included, mean age was 63.5 ± 10.8 years and mean duration of diabetes was 8.8 ± 6.6 years. Among them, 49.9% underwent orthopedic surgery and 50.1% underwent general surgery. Postoperatively, 118 (7.7%) patients had adverse events, including delayed extubation (n = 43, 36.4%), circulatory disorder (n = 15, 12.7%), respiratory and circulatory abnormalities (n = 23, 19.5%), nonhealing of the incision (n = 11, 9.3%), infections at other sites (n = 15, 12.7%), other complications (n = 8, 6.8%), and death (n = 3, 2.5%). Multivariable regression analysis showed that age >65 years old [odds ratio (OR) = 2.23, 95% confidence interval (CI): 1.25-3.98], male sex (OR = 2.14, 95% CI: 1.24-3.38), postoperative peripheral blood glucose (OR = 1.13, 95% CI: 1.13-1.82), diabetic complications (OR = 2.41, 95% CI: 1.36-4.28), abnormal kidney function (OR = 2.73, 95% CI: 1.13-6.58) and general surgery (OR = 1.48, 95% CI: 1.11-5.26) were associated with the occurrence of postoperative adverse events.In patients with diabetes undergoing intermediate or major elective surgery, older age, male sex, high postoperative peripheral blood glucose, diabetic complications, abnormal kidney function, and general surgery type were associated with the occurrence of postoperative adverse events.

Background: Physical activity is effective in preventing chronic diseases. However, the impact of different durations of exercise on human health is unknown, especially among people with diabetes or prediabetes., Objective: To explore the relationship between high MET hours per week and the change in glomerular filtration rate (eGFR) in the total population and different subgroups., Methods: A total of 43767 individuals from eight provinces, in China, were recruited. Logistic analysis was used to investigate the association. Participants were divided into 3 groups based on MET hours per week. The primary outcome was an eGFR ≤ 90 mL/min/1.73 m 2 ., Results: The average eGFR was 100.10 (92.43-106.43) mL/min/1.73 2 . Logistic regression analysis revealed that more than 7.5 MET hours per week (equivalent to more than 150 minutes of moderate-intensity of exercise) was associated with the higher risk of the decreased eGFR even after adjusting for confounding factors (7.5 to <21: OR = 1.18, 95% CI [1.09, 1.29]; ≥21: OR = 1.12, 95% CI [1.05, 1.19], p for trend: 0.0047). After adjusting for confounding factors, in stratified analyses, there still existed a significant relationship among participants aged from 55 to less than 65 years, but not among participants younger than 55 or older than 65 years. Similarly, there existed a positive association between high MET hours per week and the decreased eGFR in participants without diabetes and prediabetes, but not in participants with diabetes or prediabetes, and the interactions of age and diabetic states were found. However, there was no significant difference in women or men., Conclusions: More than 7.5 MET hours per week (equivalent to more than 150 minutes per week or 60 minutes per day of moderate-intensity exercise) was associated with decreased eGFR among participants aged from 55 to less than 65 years and participants without diabetes and prediabetes, but not among participants aged younger than 55 years and older than 65 years and participants with diabetes or prediabetes. The importance of planning individualized physical activities is highlighted.

Purpose: To systematically evaluate the quality, consistency and the evidence support of guidelines for perioperative diabetes management., Methods: We retrieved guidelines through systematic search, critically evaluated their quality and compared the recommendations of included guidelines. Five aspects were compared: target level, management of hyper- and hypoglycaemia, frequency of monitoring, management of insulin, and management of oral anti-diabetic drugs (OADs)., Results: Fourteen guidelines met our criteria, and 342 recommendations were extracted, the results of Appraisal of Guidelines for Research and Evaluation II (AGREE II) evaluation showed that none of the mean score in each domain was higher than 50%. On average, most guidelines had only one domain scored above 50%. Most recommendations (78.9%) did not specify their supporting evidence, 71 (20.8%) were formed using grading criteria, none cited systematic review or meta-analysis. Recommendations were inconsistent across different guidelines., Conclusions: The existing guidelines about perioperative management of diabetes needs improvement in methodology, as well as the production of evidence with high quality. Evidence-based guidelines are required for the perioperative management of diabetes.

Novel strategies are being developed to generate stem-cell-derived insulin-producing cells (IPCs), which could reverse the growing incidence of diabetes worldwide. We reviewed studies of stem-cell-based therapies for pancreatic β-cell regeneration published between 1997 and 2017. Differentiation into IPCs can be achieved using various stem-cell sources: embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and several types of adult stem cells such as pancreatic, hepatic and mesenchymal stem cells. However, reliable cell replacement therapy for diabetes is still in its early stages, and safety and ethical concerns are pressing issues. It will be necessary to find means of identifying optimal stem-cell sources and of inducing β-cell differentiation without using genetic mutations. The present article examines the potential of various stem-cell candidates for IPC generation, and the current obstacles preventing emergence of a candidate source., (Copyright © 2018 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Systematic review which analyzes the impact of different anesthesia on intraoperative blood glucose levels of diabetes patients., Methods: We searched Medline (via PubMed), Embase, Cochrane Library, Web of Science, Wangfang, CNKI, and CBM database through June 2016, included in randomized controlled trial (RCT), about different anesthesia on intraoperative blood glucose levels in patients with diabetes. Two researchers in 1 group independently screened literatures with eligibility criteria, extracted information, and used RevMan5.3 software to perform meta-analysis., Results: We included 11 trials and performed the meta-analysis with 10 trials. The meta-analysis results suggested that compared with general anesthesia, the combined general-epidural anesthesia has a better glycemic control in intraoperative blood glucose levels (WMD -1.26, 95% confidence interval [CI] -1.77 to 0.76), the epidural anesthesia had no significant effects compared with general anesthesia (WMD -0.74, 95% CI 4.41-2.92), and the combined spinal-epidural anesthesia had no significant effects compared with epidural anesthesia (WMD -0.28, 95% CI -1.02 to 0.46). One study suggested that compared with epidural anesthesia, the combined general-epidural anesthesia can lower blood glucose levels CONCLUSION:: Existing evidence showed that compared with general anesthesia, the combined general-epidural anesthesia has a better glycemic control in intraoperative blood glucose levels.

Background: Chronic kidney disease (CKD) increases cardiovascular disease (CVD) risk. However, the association of mildly reduced kidney function with CVD risk is unclear., Methods and Results: This study investigated the association of estimated glomerular filtration rate (eGFR) with prevalent CVDs, 10-year Framingham risk for coronary heart disease (CHD), and 10-year risk of atherosclerotic cardiovascular diseases (ASCVD) in 239 832 participants from the baseline of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study. With an interviewer-assisted questionnaire, we collected information on CVD, including reported CHD, stroke, or myocardial infarction. Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Compared with individuals with normal eGFR (≥90 mL/min per 1.73 m(2)), those with decreased eGFR (75-89, 60-74, and <60 mL/min per 1.73 m(2)) had higher risk of prevalent obesity, diabetes mellitus, hypertension, and dyslipidemia in both men and women (P for trend all <0.001). Moreover, a significantly higher 10-year Framingham risk for CHD and 10-year risk for ASCVD was observed in both men and women with mildly decreased eGFR (60-89 mL/min per 1.73 m(2))., Conclusions: Even mildly reduced eGFR (under 90 mL/min per 1.73 m(2)) is associated with elevated 10-year Framingham risk for CHD and 10-year ASCVD risk among Chinese adults., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: To investigate the impact of diabetes mellitus (DM) on survival in patients with lung cancer., Methods: This is a retrospective study of 1 096 patients died from lung cancer collected from clinical records in Chinese PLA General Hospital. Survival time of lung cancer with and without DM was compared using Log-rank analysis and Cox regression model., Results: One hundred and eighty-one patients (16.5%) had DM. The median survival time of the lung cancer patients with DM was 9 months, whereas, the median survival time of the patients without DM was 8 months. Log-rank analysis showed that this difference was significant (P<0.05). Moreover, the 1-, 2-, and 3-year survival rate in lung cancer patients with and without DM were 43% vs 35%, 27% vs 17%, and 16% vs 10%, respectively. After adjusting for age, gender, histology, stage of lung cancer and treatment, Cox regression analysis showed that the hazard ratio for survival in lung cancer patients with DM was 0.74 (95%CI 0.61-0.89, P<0.05) compared with those without DM. In non-small-cell lung cancer(NSCLC)patients, the hazard ratio for survival in lung cancer patients with DM was 0.69 (95%CI 0.56-0.85, P<0.05). However, this association disappeared in small-cell lung cancer (SCLC) patients. In advanced lung cancer patients (stage III-IV), diabetes was also a significant factor for survival (HR=0.74, 95%CI 0.61-0.91, P<0.05)., Conclusion: Patients with advanced NSCLC with DM have longer survival time compared with those without DM.

Objective: To demonstrate whether abnormal glucose metabolism (diabetes and prediabetes) is associated with increased risk for cancer in the Chinese population and to identify factors that modify the risk of cancer among individuals with abnormal glucose metabolism., Methods: Between 2011 and 2012, 259 657 community-dwelling adults, aged 40 years and older, were recruited from 25 centers across mainland China to participant in the baseline survey of the REACTION study, with follow-up investigations performed 3, 5, and 10 years later. Detailed questionnaires about lifestyles, physical and biochemical measurement, bio-samples including serum, urine, and whole blood for DNA extraction were collected for all the participants., Results: The mean ± standard deviation (SD) age of this cohort was 57 ± 10 years. And the prevalence of pre-existing and newly diagnosed diabetes was 10.32% and 10.57%, respectively. A total of 4511 prevalent cancer cases (988 men and 3523 women) were identified, the prevalence was 1.79. Compared to those with normal glucose metabolism, men with diabetes had a significantly lower adjusted prevalence ratio (PR) of stomach cancer (PR: 0.38, 95% CI: 0.16-0.89), and women with diabetes had significantly higher adjusted PRs of cancer of all sites (PR: 1.36, 95% CI: 1.20-1.56), and cancer of the breast (PR: 1.56, 95% CI: 1.21-2.00), the endometrium (PR: 1.58, 95% CI: 1.16-2.15), and the thyroid (PR: 1.53, 95% CI: 1.03-2.27)., Conclusion: The multi-center REACTION study has captured a broad range of data on physical, psychological and metabolic function as well as health status, biochemical and lifestyle information in 259 657 adults from the general population across the China., (© 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Importance: Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide., Objective: To investigate the prevalence of diabetes and glycemic control in the Chinese adult population., Design, Setting, and Participants: Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010., Main Outcomes and Measures: Plasma glucose and hemoglobin A1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A1c level of <7.0% was considered adequate glycemic control., Results: The overall prevalence of diabetes was estimated to be 11.6% (95% CI, 11.3%-11.8%) in the Chinese adult population. The prevalence among men was 12.1% (95% CI, 11.7%-12.5%) and among women was 11.0% (95% CI, 10.7%-11.4%). The prevalence of previously diagnosed diabetes was estimated to be 3.5% (95% CI, 3.4%-3.6%) in the Chinese population: 3.6% (95% CI, 3.4%-3.8%) in men and 3.4% (95% CI, 3.2%-3.5%) in women. The prevalence of undiagnosed diabetes was 8.1% (95% CI, 7.9%-8.3%) in the Chinese population: 8.5% (95% CI, 8.2%-8.8%) in men and 7.7% (95% CI, 7.4%-8.0%) in women. In addition, the prevalence of prediabetes was estimated to be 50.1% (95% CI, 49.7%-50.6%) in Chinese adults: 52.1% (95% CI, 51.5%-52.7%) in men and 48.1% (95% CI, 47.6%-48.7%) in women. The prevalence of diabetes was higher in older age groups, in urban residents, and in persons living in economically developed regions. Among patients with diabetes, only 25.8% (95% CI, 24.9%-26.8%) received treatment for diabetes, and only 39.7% (95% CI, 37.6%-41.8%) of those treated had adequate glycemic control., Conclusions and Relevance: The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6% and the prevalence of prediabetes was 50.1%. Projections based on sample weighting suggest this may represent up to 113.9 million Chinese adults with diabetes and 493.4 million with prediabetes. These findings indicate the importance of diabetes as a public health problem in China.

Background: Sleep duration affects health in various ways. The objective of the present study was to investigate the relationships among sleep duration, daytime napping and kidney function in a middle-aged apparently healthy Chinese population. Methods: According to self-reported total sleep and daytime napping durations, 33,850 participants who were 38–90 years old and recruited from eight regional centers were divided into subgroups. Height, weight, waist circumference, hip circumference, blood pressure, biochemical indexes, fasting blood glucose (FBG), postprandial blood glucose (PBG), HbA1c, creatinine and urinary albumin-creatinine ratio (UACR) were measured and recorded for each subject. Microalbuminuria was defined as UACR ≥30 mg/g, chronic kidney disease (CKD) was defined as eGFR <60 ml/min, and hyperfiltration was defined as eGFR ≥135 ml/min. Multiple logistic regression was applied to investigate the association between sleep and kidney function. Results: Compared to sleeping for 7–8 h/day, the ORs for microalbuminuria for sleeping for >9 h/day, 8–9 h/day 6–7 h/day and <6 h/day were 1.343 (1.228–1.470, P<0.001), 1.223 (1.134–1.320, P<0.001), 1.130 (1.003–1.273, P = 0.045) and 1.140 (0.908–1.431, P = 0.259), respectively. The eGFR levels exhibited a U-shaped association with sleep duration among subjects with an eGFR ≥90 ml/min and an N-shaped association with sleep duration among subjects with an eGFR <90 ml/min. The OR for hyperfiltration for >9 h/day of sleep was 1.400 (1.123–1.745, P = 0.003) among participants with an eGFR ≥90 ml/min. Daytime napping had a negative effect on renal health. Compared to the absence of a napping habit, the ORs for microalbuminuria for 0–1 h/day, 1–1.5 h/day and >1.5 h/day of daytime napping were 1.552 (1.444–1.668, P<0.001), 1.301 (1.135–1.491, P<0.001) and 1.567 (1.353–1.814, P<0.001), respectively. Conclusion: The association of total sleep duration with renal health outcomes is U-shaped. Daytime napping has a negative effect on renal health. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases. [ABSTRACT FROM AUTHOR]

Objective: To estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China. Methods: The Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs. Health insurance costs (2015¥) were estimated over 40 years from a healthcare payer perspective. Univariate and probabilistic sensitivity analyses were performed. Results: The model predicted that dapagliflozin had lower incidences of cardiovascular events, hypoglycemia and mortality events, was associated with a mean incremental benefit of 0.25 quality-adjusted life-years (QALYs) and with a lower cost of ¥8,439 compared with acarbose. This resulted in a cost saving of ¥33,786 per QALY gained with dapagliflozin. Sensitivity analyses determined that the results are robust. Conclusion: Dapagliflozin is dominant compared with acarbose as monotherapy for Chinese T2DM patients, with a little QALY gain and lower costs. Dapagliflozin offers a well-tolerated and cost-effective alternative medication for treatment-naive patients in China, and may have a direct impact in reducing the disease burden of T2DM. [ABSTRACT FROM AUTHOR]

Objectives: To explore the relationship between depressive symptoms and waist-to-hip ratio, dyslipidemia, glycemic levels or blood pressure among diabetic and non-diabetic Chinese women. Methods: 11,908 women aged ≥40 years were enrolled in this cross-sectional study, including 2,511 with type 2 diabetes and 9,397 without. Depressive symptoms (defined as having mild-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 (PHQ-9) diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having depressive symptoms were estimated using logistic regression analysis. Results: The age-adjusted prevalence of depressive symptoms was significantly higher in non-diabetic subjects with waist-to-hip ratio (WHR) ≥0.9 (8.6%, age-adjusted OR 1.51 [95% CI 1.17, 1.95]), total cholesterol (TC)>6.22 mmol/L (8.8%, 1.58 [1.16, 2.15]), and Hemoglobin A1c (HbA1c) ≥6.00 mmol/L (7.7%, 1.69 [1.34, 2.14]), while it was significantly lower in non-diabetic subjects with diastolic blood pressure (DBP) between 80 to 89 mmHg (6.2%, 0.78 [0.64, 0.95]). These relationships remained significant even after controlling for multiple factors (WHR ≥0.9: multivariable-adjusted OR 1.39 [95% CI 1.07, 1.80]; TC>6.22 mmol/L: 1.56 [1.14, 2.12]; HbA1c ≥6.00 mmol/L: 1.64 [1.30, 2.08]; DBP 80-89 mmHg: 0.78 [0.64, 0.95]). However, no significant trend between depressive symptoms and WHC, TC, HbA1c, DBP was observed in diabetic women, and no significant trend relationship between depressive symptoms and BMI, WC, TG, or SBP was observed in both non-diabetic and diabetic women. Moreover, the prevalence of depressive symptoms was significantly higher in previously-diagnosed diabetes, compared with non-diabetic subjects, while no significant differences were observed between newly-diagnosed diabetes and non-diabetic subjects. Conclusion: The present study showed a relationship between WHR, TC, HbA1c, DBP and depressive symptoms among non-diabetic women, while no significant relationship between them was observed among diabetic women, even after controlling for multiple confounding factors. [ABSTRACT FROM AUTHOR]

This study was designed to assess whether the combination of the glucagon-like peptide-1 (GLP-1) analog exendin-4 (Ex4) and bone marrow-derived mesenchymal stem cell (BM-MSC) could enhance β-cell action in streptozotocin (STZ)-induced diabetic rats. Forty male Sprague–Dawley rats were randomly assigned to five groups: the normal control group (Normal), diabetes mellitus (DM) group, MSC-treated group (MSC), Ex4-treated group (Ex4), and MSC plus Ex4-treated group (MSC+Ex4). Body weight, blood glucose level, intraperitoneal glucose tolerance test, and in vitro glucose-stimulated insulin secretion were used to assess the treatment efficacy. The expression level of insulin, glucagon, pancreatic duodenal homeobox-1 (PDX-1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), glucagon-like peptide-1 receptor (GLP-1R), and forkhead transcription factor 1 (FoxO1) was estimated by immunofluorescence analysis. Proliferation was assessed by Ki67 staining, and apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in β-cells. Glucose-induced insulin secretion in the MSC+Ex4 group was significantly increased compared to that in the MSC group in vitro and in vivo. Compared to that of the other groups, the number of insulin-immunopositive cells was increased in both the MSC and MSC+Ex4 groups. However, β-cell proliferation and apoptosis in the MSC group and MSC+Ex4 group were not significantly different. Importantly, the expression level of PDX-1, MafA, FoxO1, and GLP-1R in β-cells in the MSC+Ex4 group was significantly higher than those in the MSC group. The numbers of insulin+ glucagon+ double positive cells and glucagon+ GLP-1+ double positive cells were significantly increased after MSC treatment and MSC+Ex4 combined treatment, suggesting the enhanced function of newly formed islet β-cells. Our findings showed that the combination of MSC and Ex4 enhanced the function of newly formed β-cells in STZ-induced diabetic rats by acting on multiple insulin transcription factors. Thus, combined MSC and Ex4 therapy provides a feasible approach for future diabetes treatments. [ABSTRACT FROM AUTHOR]