Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are cur-rently being investigated to create insulin-producing β cells to replace deficient β cells, including the ...Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are cur-rently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.展开更多
Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We includ...Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.展开更多
The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown.This study aimed to investigate this association in a community-dwelling population aged≥40 years in Shangha...The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown.This study aimed to investigate this association in a community-dwelling population aged≥40 years in Shanghai,China.Oral glucose tole3rance test was conducted during baseline and follow-up visits.Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk.A total of 613(10.3%)incident diabetes cases were identified during the follow-up visit after 4.5 years.Fasting plasma glucose,postload glucose,and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid(all Ps<0.05).The incidence rate of diabetes increased across the quartiles of serum uric acid(7.43%,8.77%,11.47%,and 13.43%).Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid(odds ratio(95%confidence interval)=1.36(1.06−1.73)).Stratified analysis indicated that the association was only observed in women.Accordingly,serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.展开更多
A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been proposed.We aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease...A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been proposed.We aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease(NAFLD),with the progression of elevated brachial-ankle pulse wave velocity(baPWV)and albuminuria in a community-based study sample in Shanghai,China.After 4.3 years of follow-up,778 participants developed elevated baPWV and 499 developed albuminuria.In comparison with the non-MAFLD group,the multivariable adjusted odds ratio(OR)of MAFLD group for new-onset elevated baPWV was 1.25(95%confidence interval(CI)1.01–1.55)and 1.35(95%CI 1.07–1.70)for albuminuria.Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria(OR 1.77;95%CI 1.07–2.94).Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria.In conclusion,MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index,waist circumference,and hip circumference.Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria,supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.展开更多
Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323...Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323 community-dwelling subjects aged⩾40 years from China.Early-life famine exposure was identified based on the participants’birth dates.General obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or lower.Compared to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in men.Significant interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.展开更多
基金Supported by The Agence National de Recherche(ANR 2010 BLAN 1240 01)the Ligue contre le Cancer du Rh ne and de la Loire+3 种基金the CMIRA program of Region Rh?ne-Alpes,No.12004959-01the Fondation ARC pour la Recherche sur le Cancer,France,No.SFI20101201530National Nature Science Foundation of China,No.NSFC81170719,No.81370960Shanghai New Excellent Youth Program,No.XYQ2011009
文摘Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are cur-rently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.
基金supported by the grants from the National Natural Science Foundation of China(Nos.82088102,91857205,82022011,81970728,and 81930021)the Shanghai Rising-Star Program(No.21QA1408100)+2 种基金Shanghai Outstanding Academic Leaders Plan(No.20XD1422800)the National Top Young Scholar Program(Yu Xu),the Innovative Research Team of High-Level Local Universities in Shanghai,the Shanghai Clinical Research Center for Metabolic Diseases(No.19MC1910100)the Shanghai Shen Kang Hospital Development Center(Nos.SHDC2020CR1001A and SHDC2020CR3064B).
文摘Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD.We included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life behavior.Using isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD prevalence.Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population.In stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long sleepers.More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active way.The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical activity.The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.
基金This study was supported by the Ministry of Science and Technology of the People's Republic of China(Nos.2016YFC1305202 and 2016YFC1304904)National Natural Science Foundation of China(Nos.81670795 and 81870604)Yuhong Chen was supported by the Shanghai Shenkang Hospital Development Center for improving the control of type 2 diabetes in the suburbs of Shanghai(No.16CR4020A).
文摘The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown.This study aimed to investigate this association in a community-dwelling population aged≥40 years in Shanghai,China.Oral glucose tole3rance test was conducted during baseline and follow-up visits.Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk.A total of 613(10.3%)incident diabetes cases were identified during the follow-up visit after 4.5 years.Fasting plasma glucose,postload glucose,and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid(all Ps<0.05).The incidence rate of diabetes increased across the quartiles of serum uric acid(7.43%,8.77%,11.47%,and 13.43%).Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid(odds ratio(95%confidence interval)=1.36(1.06−1.73)).Stratified analysis indicated that the association was only observed in women.Accordingly,serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.
基金This work was supported by the grants from the National Key R&D Program of China(Nos.2017YFC1310700,2018YFC1311800,and 2018YFC1311705)the National Natural Science Foundation of China(Nos.81870560,82070880,81941017,81770842,81970706,and 82022011)+6 种基金the National Science and Technology Major Project for"Significant New Drugs Development"(No.2017ZX09304007)Shanghai Municipal Government(No.18411951800)Shanghai Shenkang Hospital Development Center(Nos.SHDC12019101,SHDC2020CR1001A,and SHDC2020CR3069B)the Scientific and Technological Committee of Shanghai(No.19411964200)Shanghai Jiao Tong University School of Medicine(No.DLY201801)Ruijin Hospital(No.2018 CR002)Shanghai Rising-Star Program(No.21QA1408100).
文摘A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been proposed.We aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease(NAFLD),with the progression of elevated brachial-ankle pulse wave velocity(baPWV)and albuminuria in a community-based study sample in Shanghai,China.After 4.3 years of follow-up,778 participants developed elevated baPWV and 499 developed albuminuria.In comparison with the non-MAFLD group,the multivariable adjusted odds ratio(OR)of MAFLD group for new-onset elevated baPWV was 1.25(95%confidence interval(CI)1.01–1.55)and 1.35(95%CI 1.07–1.70)for albuminuria.Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria(OR 1.77;95%CI 1.07–2.94).Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria.In conclusion,MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index,waist circumference,and hip circumference.Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria,supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
基金supported by grants from the National Natural Science Foundation of China (Nos.81471062,81471059, 81500660,and 81561128019)the Ministry of Science and Technology of China (Nos.2016YFC1305600,2016YFC1304904, and 2018YFC1311705)+1 种基金the National International Science Cooperation Foundation (No.2015DFA30560) the Gaofeng Clinical Medicine Grant Support of the Shanghai Municipal Education Commission (Nos.20152508and 20161301).
基金supported by the Ministry of Science and Technology of China(No.2022YFC2505202)the National Natural Science Foundation of China(Nos.81970691 and 82170819)+4 种基金Shanghai Outstanding Academic Leaders Plan(No.20XD1422800)Shanghai Medical and Health Development Foundation(No.DMRFP_I_01)Clinical Research Plan of SHDC(No.SHDC2020CR3064B)Science and Technology Committee of Shanghai(No.20Y11905100)Key Medical Subject of Jiading District,Shanghai(No.2020-jdyxzdzk-01).
文摘Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown.This study included 5323 community-dwelling subjects aged⩾40 years from China.Early-life famine exposure was identified based on the participants’birth dates.General obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or lower.Compared to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in men.Significant interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.