Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T...Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.展开更多
Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats...Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.展开更多
Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and n...Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.展开更多
To investigate the effects of hypoxic exercise training on microRNA (miRNA) expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic s...To investigate the effects of hypoxic exercise training on microRNA (miRNA) expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group (N, n=10) and a hypoxic exercise training group (H, n=10). After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of perexisome proliferator activated receptor a (PPARα), fatty acid synthetase (FAS), and carnitine palmitoyl transferase 1A (CPTIA) in rat liver. Body weight, Lee's index, fat mass, fat/weight ratio, and serum levels of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were all significantly lower in the H group than in the N group (P〈0.01). Six miRNAs expressed significantly differently in the liver (P〈0.05). Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group (P〈0.05). Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPTIA mRNA (P〈0.05), as well as lower CPT1A protein levels (P〈0.01), while a higher ratio of FAS to CPT1A protein levels (P〈0.01) was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPTIA and increasing the protein expression ratio of FAS/CPTIA.展开更多
Background:Non-communicable chronic diseases have become the leading causes of disease burden worldwide.The trends and burden of“metabolic associated fatty liver disease”(MAFLD)are unknown.We aimed to investigate th...Background:Non-communicable chronic diseases have become the leading causes of disease burden worldwide.The trends and burden of“metabolic associated fatty liver disease”(MAFLD)are unknown.We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease(NAFLD).Methods:Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged≥20years from the cross-sectional US National Health and Nutrition Examination Survey periods,1999 to 2002,2003 to 2006,2007 to 2010,and 2011 to 2016.MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity,type 2 diabetes mellitus,or evidence of metabolic dysregulation.Results:The prevalence of MAFLD increased from 28.4%(95% confidence interval 26.3–30.6)in 1999 to 2002 to 35.8%(33.8–37.9)in 2011 to 2016.In 2011 to 2016,among adults with MAFLD,49.0%(45.8–52.2)had hypertension,57.8%(55.2–60.4)had dyslipidemia,26.4%(23.9–28.9)had diabetes mellitus,88.7%(87.0–80.1)had central obesity,and 18.5%(16.3–20.8)were current smokers.The 10-year cardiovascular risk ranged from 10.5%to 13.1%;19.7%(17.6–21.9)had chronic kidney diseases(CKDs).Throughthe fourperiods,adults withMAFLD showedanincrease in obesity;increase intreatment to lower bloodpressure(BP),lipids,and hemoglobin A1c;and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus.Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs,myocardial infarction,or stroke.Generally,although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD,the prevalence of MAFLD was significantly higher than that of NAFLD.Conclusions:From 1999 to 2016,cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD.The absolute cardiorenal burden may be greater for MAFLD than for NAFLD.These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.展开更多
Background:China has experienced rapid urbanization in the past 30 years.We aimed to report blood cadmium level(BCL)in the rapidly urbanized Yangtze Plain of China,and explore the association between BCL and 25-hydrox...Background:China has experienced rapid urbanization in the past 30 years.We aimed to report blood cadmium level(BCL)in the rapidly urbanized Yangtze Plain of China,and explore the association between BCL and 25-hydroxyvitamin D(25(OH)D).Methods:Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors(SPECT-China)cross-sectional study(ChiCTR-ECS-14005052,www.chictr.org).We enrolled 3234 subjects from 12 villages in the Yangtze Plain.BCLs were measured by atomic absorption spectrometry.25(OH)D was measured with a chemiluminescence assay.Results:A total of 2560(79.2%)subjects were diagnosed with vitamin D deficiency.The median(interquartile range)BCL was 1.80μg/L(0.60-3.42)for men and 1.40μg/L(0.52-3.10)for women.In women,mean 25(OH)D concentrations were inversely associated with BCL(0.401,95%confidence interval:-0.697 to-0.105 nmol/L lower with each doubling of the BCL)after adjustment for age,educational status,current smoking,body mass index,diabetes,and season.However,there was no significant difference in 25(OH)D across the BCL tertiles for men.Conclusions:BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries.An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment.Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships,and to elucidate the exact mechanisms involved.展开更多
基金supported by the National Natural Science Foundation of China(No.82120108008,No.91857117)the Project of Biobank(No.YBKA201909)from Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicinea grant from Shanghai Jiaotong University School of Medicine(No.19XJ11007).
文摘Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.
基金Acknowledgment This study was support by Natural Science Foundation of Shanghai, China (No. 06ZR14137).
文摘Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.
基金grants from the National Natural Science Foundation of China(No.81270885,No.81570726 and No.81600609)Shanghai Jiao Tong University School of Medicine(2014)+4 种基金the Ministry of Science and Technology in China(No.2012CB524906)the Science and Technology Commission of Shanghai Municipality(No.14495810700 and No.16410723200)Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning(2015-2017)Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine(2014),Shanghai Municipal Health Bureau of China(No.20124262)Seed Founding of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(No.JYZZ032).
文摘Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.
基金Project supported by the Science Foundation for the Youth of China Institute of Sport Science (CISS) (No. 13-19)
文摘To investigate the effects of hypoxic exercise training on microRNA (miRNA) expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group (N, n=10) and a hypoxic exercise training group (H, n=10). After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of perexisome proliferator activated receptor a (PPARα), fatty acid synthetase (FAS), and carnitine palmitoyl transferase 1A (CPTIA) in rat liver. Body weight, Lee's index, fat mass, fat/weight ratio, and serum levels of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were all significantly lower in the H group than in the N group (P〈0.01). Six miRNAs expressed significantly differently in the liver (P〈0.05). Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group (P〈0.05). Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPTIA mRNA (P〈0.05), as well as lower CPT1A protein levels (P〈0.01), while a higher ratio of FAS to CPT1A protein levels (P〈0.01) was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPTIA and increasing the protein expression ratio of FAS/CPTIA.
基金supported by the National Natural Science Foundation of China(No.91857117)the Science and Technology Commission of Shanghai Municipality(Nos.19140902400,18410722300).
文摘Background:Non-communicable chronic diseases have become the leading causes of disease burden worldwide.The trends and burden of“metabolic associated fatty liver disease”(MAFLD)are unknown.We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease(NAFLD).Methods:Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged≥20years from the cross-sectional US National Health and Nutrition Examination Survey periods,1999 to 2002,2003 to 2006,2007 to 2010,and 2011 to 2016.MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity,type 2 diabetes mellitus,or evidence of metabolic dysregulation.Results:The prevalence of MAFLD increased from 28.4%(95% confidence interval 26.3–30.6)in 1999 to 2002 to 35.8%(33.8–37.9)in 2011 to 2016.In 2011 to 2016,among adults with MAFLD,49.0%(45.8–52.2)had hypertension,57.8%(55.2–60.4)had dyslipidemia,26.4%(23.9–28.9)had diabetes mellitus,88.7%(87.0–80.1)had central obesity,and 18.5%(16.3–20.8)were current smokers.The 10-year cardiovascular risk ranged from 10.5%to 13.1%;19.7%(17.6–21.9)had chronic kidney diseases(CKDs).Throughthe fourperiods,adults withMAFLD showedanincrease in obesity;increase intreatment to lower bloodpressure(BP),lipids,and hemoglobin A1c;and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus.Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs,myocardial infarction,or stroke.Generally,although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD,the prevalence of MAFLD was significantly higher than that of NAFLD.Conclusions:From 1999 to 2016,cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD.The absolute cardiorenal burden may be greater for MAFLD than for NAFLD.These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.
基金supported by grants from the National Natural Science Foundation of China(No.81600609)Science and Technology Commission of Shanghai Municipality(No.18410722300)+2 种基金Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai(No.2017YQ053)Fundamental Research Program Funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(No.JYZZ099)Shanghai Sailing Program(No.20YF1423500)。
文摘Background:China has experienced rapid urbanization in the past 30 years.We aimed to report blood cadmium level(BCL)in the rapidly urbanized Yangtze Plain of China,and explore the association between BCL and 25-hydroxyvitamin D(25(OH)D).Methods:Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors(SPECT-China)cross-sectional study(ChiCTR-ECS-14005052,www.chictr.org).We enrolled 3234 subjects from 12 villages in the Yangtze Plain.BCLs were measured by atomic absorption spectrometry.25(OH)D was measured with a chemiluminescence assay.Results:A total of 2560(79.2%)subjects were diagnosed with vitamin D deficiency.The median(interquartile range)BCL was 1.80μg/L(0.60-3.42)for men and 1.40μg/L(0.52-3.10)for women.In women,mean 25(OH)D concentrations were inversely associated with BCL(0.401,95%confidence interval:-0.697 to-0.105 nmol/L lower with each doubling of the BCL)after adjustment for age,educational status,current smoking,body mass index,diabetes,and season.However,there was no significant difference in 25(OH)D across the BCL tertiles for men.Conclusions:BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries.An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment.Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships,and to elucidate the exact mechanisms involved.