Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders.These people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecu...Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders.These people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain elusive.Rab18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and maturation.In the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice.Rab18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype mice.When subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in SAT.In contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress stimulation.Rab18 AKO mice developed insulin resistance and systematic inflammation.Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart mice.Furthermore,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid toxicity.Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT.In conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.展开更多
The increasing prevalence of diabetes has become a global public health concern in the 21st century.In 2021,it was estimated that 537 million people had diabetes,and this number is projected to reach 643 million by 20...The increasing prevalence of diabetes has become a global public health concern in the 21st century.In 2021,it was estimated that 537 million people had diabetes,and this number is projected to reach 643 million by 2030,and 783 million by 2045[1].Such a huge burden of diabetes brings great challenges in its prevention and management,including early diagnosis,timely interventions,and regular monitoring of risk factor control and complications screening.Continuous self-care support and patient empowerment can enhance clinical and psychobehavioural outcomes[2],although these require additional resources including manpower,infrastructure(hard and technology),and finances.The emergence of digital health technologies(DHTs),especially artificial intelligence(AI),may help address these obstacles and alleviate the burden of diabetes[3].Large language models(LLMs),a generative AI that can accept image and text inputs and produce text outputs,have shown promise in various aspects of medical care.展开更多
Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk.As a new parame...Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk.As a new parameter for continuously evaluating personal clinical statuses,the newly developed technique“continuous glucose monitoring”(CGM)can characterize glucose dynamics.By calculating the complexity of glucose time series index(CGI)with refined composite multi-scale entropy analysis of the CGM data,the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes(P for trend<0.01).Furthermore,CGI was significantly associated with various parameters such as insulin sensitivity/secretion(all P<0.01),and multiple linear stepwise regression showed that the disposition index,which reflectsβ-cell function after adjusting for insulin sensitivity,was the only independent factor correlated with CGI(P<0.01).Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.展开更多
A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause.Here,we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesit...A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause.Here,we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes.We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing(WES)data available for 146 of these patients.The coverage of targeted gene panel sequencing was significantly higher than that of WES.The diagnostic yield in patients sequenced by the panel was 32.9%with subsequent WES leading to three additional diagnoses with two novel genes.In total,178 variants in 83 genes were detected in 146 patients by targeted sequencing.Three of the 178 variants were missed by WES,although the WES-only approach had a similar diagnostic yield.For the 335 samples only receiving targeted sequencing,the diagnostic yield was 32.2%.In conclusion,taking into account the lower costs,shorter turnaround time,and higher quality of data,targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES.Therefore,this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.展开更多
Obesity is closely related to non-alcoholic fatty liver disease(NAFLD).Although sex differences in body fat distribution have been well demonstrated,little is known about the sex-specific associations between adipose ...Obesity is closely related to non-alcoholic fatty liver disease(NAFLD).Although sex differences in body fat distribution have been well demonstrated,little is known about the sex-specific associations between adipose tissue and the development of NAFLD.Using community-based cohort data,we evaluated the associations between magnetic resonance imaging quantified areas of abdominal adipose tissue,including visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT),and incident NAFLD in 2830 participants(1205 males and 1625 females)aged 55–70 years.During a 4.6-year median follow-up,the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and in females.Further analyses showed that the abovementioned positive associations were stronger in males than in females,especially in participants under 60 years old.In contrast,these sex differences disappeared in those over 60 years old.Furthermore,the risk of developing NAFLD increased non-linearly with increasing fat area in a sex-specific pattern.Additionally,sex-specific potential mediators,such as insulin resistance,lipid metabolism,inflammation,and adipokines,may exist in the associations between adipose tissue and NAFLD.This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age,highlighting the potential need for sex-and age-specific management of NAFLD.展开更多
Dear Editor,Obesity is a major health issue with global prevalence and increases the risk of many metabolic diseases.Of particular con-cern is the increasing incidence of type 2 diabetes,the primary causes of which ar...Dear Editor,Obesity is a major health issue with global prevalence and increases the risk of many metabolic diseases.Of particular con-cern is the increasing incidence of type 2 diabetes,the primary causes of which are obesity-driven insulin resistance in white adipose tissue(WAT),skeletal muscle,and liver,and decreased insulin secretion by pancreaticβ-cells[1].展开更多
Background: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which...Background: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM).Methods: In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm2.Results: Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P< 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595–0.866,P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (allP for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients.Conclusions: There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.展开更多
This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the analysis.Profiles of risk factors and inte...This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the analysis.Profiles of risk factors and intermediate outcomes were determined.The patients had a mean age of 66.43±8.12(standard deviation(SD))years and a mean diabetes duration of 7.95±5.53(SD)years.The percentage of patients who achieved the target level for HbA_(1c)(<7.0%)was 48.6%.Patients who achieved the target levels for blood pressure(BP)<130/80 mmHg and low-density lipoprotein-cholesterol(LDL-c)<2.6 mmol/L reached 17.5%and 34.0%,respectively.A total of 3.8%achieved all three target levels,and the value increased to 6.8%with an adaptation of the BP target level(<140/90 mmHg)for those over 65 years.Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels:male,young age,short diabetes duration,low body mass index,macrovascular complications,no microvascular complications,prescribed with lipid-lowering medication,and no prescription of antihypertensive medication.In conclusion,nearly 50%and one-third of the patients with diabetes met the target levels for HbA_(1c)and LDL-c,respectively,with a low percentage achieving the BP target level.The percentage of patients who achieved all three target levels needs significant improvement.展开更多
Background: The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association b...Background: The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between β cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes.Methods: This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on β cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of β cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models.Results: Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively (P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16-1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for β cell function (HOMA-β) were 1.00, 0.51, 0.60, and 0.53, respectively (P for trend = 0.068). When HOMA-β was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24-0.90) for each 1-unit increase in HOMA-β. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes.Conclusions: We demonstrated a significant association of β cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values.展开更多
Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a mu...Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a multinational,multicenter,randomized,double-blind,treat-to-target,26-week,phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes(T2D).After an 8-week lead-in period during which basal insulin glargine or degludec was optimized,adults with T2D were randomized(2:1)to prandial URLi(n=395)or lispro(n=200).The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c(HbA_(1c))change from baseline to week 26.Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1-and 2-h PPG excursions during a mixed-meal tolerance test(MMTT)and HbA_(1c) change at week 26.URLi showed non-inferiority for Hb Achange at week 26 versus lispro(least-squares mean[LSM]difference,0.07%;95%confidence interval:-0.07,0.21).HbA_(1c) was reduced by 0.56%and 0.63%with URLi and lispro,respectively,with no significant treatment difference(P=0.321).URLi provided superior PPG excursion control versus lispro at1 h(LSM difference:-14.6 mg/d L,P<0.001)and 2 h(LSM difference:-21.8 mg/d L,P<0.001)as well as other time points(30–240 min)during the MMTT.Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro.The safety profiles were generally similar between treatment groups.In conclusion,URLi was superior to lispro for PPG control,with noninferiority in HbA_(1c) improvement,in adults with T2D.展开更多
Lifestyle interventions,including dietary adjustments and exercise,are important for obesity management.This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exer...Lifestyle interventions,including dietary adjustments and exercise,are important for obesity management.This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exercise is more effective in metabolism improvement.Forty-five eligible subjects were randomly divided into an LCD group(n=22)and an exercise group(EX,n=23).The subjects either adopted LCD(carbohydrate intake<50 g/day)or performed moderate-to-vigorous exercise(≥30 min/day)for 3 weeks.After the interventions,LCD led to a larger weight loss than EX(−3.56±0.37 kg vs.−1.24±0.39 kg,P<0.001),as well as a larger reduction in fat mass(−2.10±0.18 kg vs.−1.25±0.24 kg,P=0.007)and waist circumference(−5.25±0.52 cm vs.−3.45±0.38 cm,P=0.008).Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance.Triglycerides decreased in both two groups,whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group.Various glycemic parameters,including serum glycated albumin,mean sensor glucose,coefficient of variability(CV),and largest amplitude of glycemic excursions,substantially declined in the LCD group.Only CV slightly decreased after exercise.This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance.Compared with exercise,LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.展开更多
Obesity and its related complications comprise a serious public health problem worldwide,and obesity is increasing in China.Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesit...Obesity and its related complications comprise a serious public health problem worldwide,and obesity is increasing in China.Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications.The pathogenesis of obesity is complex and not yet fully understood.Here,we review the current efficacy and safety of metabolic surgery,as well as recent progress in mechanistic studies and surgical procedures in China.The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.展开更多
基金supported by the National Key Research and Development Program of China(2018YFA0506901,2019YFA0801701,2022YFA0806502)the National Natural Science Foundation of China(92254308,92157107)the Lingang Laboratory(LG-QS-202204-06)。
文摘Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders.These people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain elusive.Rab18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and maturation.In the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice.Rab18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype mice.When subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in SAT.In contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress stimulation.Rab18 AKO mice developed insulin resistance and systematic inflammation.Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart mice.Furthermore,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid toxicity.Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT.In conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.
基金supported by the National Key R&D Program of China(2022YFC2502800 and 2022YFC2407000)the National Natural Science Foundation of China(8238810007,82022012,81870598 and 62272298)+3 种基金the Shanghai Municipal Key Clinical SpecialtyShanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)the Chinese Academy of Engineering(2022-XY-08)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20212700)。
文摘The increasing prevalence of diabetes has become a global public health concern in the 21st century.In 2021,it was estimated that 537 million people had diabetes,and this number is projected to reach 643 million by 2030,and 783 million by 2045[1].Such a huge burden of diabetes brings great challenges in its prevention and management,including early diagnosis,timely interventions,and regular monitoring of risk factor control and complications screening.Continuous self-care support and patient empowerment can enhance clinical and psychobehavioural outcomes[2],although these require additional resources including manpower,infrastructure(hard and technology),and finances.The emergence of digital health technologies(DHTs),especially artificial intelligence(AI),may help address these obstacles and alleviate the burden of diabetes[3].Large language models(LLMs),a generative AI that can accept image and text inputs and produce text outputs,have shown promise in various aspects of medical care.
基金the National Natural Science Foundation of China(Nos.81873646 and 61903071)the Shanghai United Developing Technology Project of Municipal Hospitals(Nos.SHDC12006101 and SHDC12010115)the Shanghai Municipal Education Commission Gaofeng Clinical Medicine grant support(Nos.20161430).
文摘Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk.As a new parameter for continuously evaluating personal clinical statuses,the newly developed technique“continuous glucose monitoring”(CGM)can characterize glucose dynamics.By calculating the complexity of glucose time series index(CGI)with refined composite multi-scale entropy analysis of the CGM data,the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes(P for trend<0.01).Furthermore,CGI was significantly associated with various parameters such as insulin sensitivity/secretion(all P<0.01),and multiple linear stepwise regression showed that the disposition index,which reflectsβ-cell function after adjusting for insulin sensitivity,was the only independent factor correlated with CGI(P<0.01).Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.
基金supported by grants from Shanghai Outstanding Academic Leaders(20XD1433300)Medical-Engineering Cross Foundation of Shanghai Jiao Tong University(YG2021ZD20)+3 种基金Shuguang Project(21SG11),Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20212700)Shanghai Research Center for Endocrine,Metabolic Diseases(2022ZZ01002)Shanghai Sixth People’s Hospital Grant(ynhg202204)Shanghai Municipal Key Clinical Specialty.
文摘A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause.Here,we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes.We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing(WES)data available for 146 of these patients.The coverage of targeted gene panel sequencing was significantly higher than that of WES.The diagnostic yield in patients sequenced by the panel was 32.9%with subsequent WES leading to three additional diagnoses with two novel genes.In total,178 variants in 83 genes were detected in 146 patients by targeted sequencing.Three of the 178 variants were missed by WES,although the WES-only approach had a similar diagnostic yield.For the 335 samples only receiving targeted sequencing,the diagnostic yield was 32.2%.In conclusion,taking into account the lower costs,shorter turnaround time,and higher quality of data,targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES.Therefore,this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.
基金supported by Shanghai Key Clinical Center for Metabolic Disease(2017ZZ01013)Shanghai Municipal Key Clinical Specialty,the National Natural Science Foundation of China-National Health and Medical Research Council joint research grant(81561128016)+4 种基金the Natural Science Foundation of Shanghai(18ZR1429000)Shanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)Shanghai Key Discipline of Public Health(GWVI-11.1-20)Shanghai Health Commission(JKKPYC-2022-12)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38020000 and XDB38000000).
文摘Obesity is closely related to non-alcoholic fatty liver disease(NAFLD).Although sex differences in body fat distribution have been well demonstrated,little is known about the sex-specific associations between adipose tissue and the development of NAFLD.Using community-based cohort data,we evaluated the associations between magnetic resonance imaging quantified areas of abdominal adipose tissue,including visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT),and incident NAFLD in 2830 participants(1205 males and 1625 females)aged 55–70 years.During a 4.6-year median follow-up,the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and in females.Further analyses showed that the abovementioned positive associations were stronger in males than in females,especially in participants under 60 years old.In contrast,these sex differences disappeared in those over 60 years old.Furthermore,the risk of developing NAFLD increased non-linearly with increasing fat area in a sex-specific pattern.Additionally,sex-specific potential mediators,such as insulin resistance,lipid metabolism,inflammation,and adipokines,may exist in the associations between adipose tissue and NAFLD.This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age,highlighting the potential need for sex-and age-specific management of NAFLD.
基金This study was supported by grants from the National Key Research and Development Program of China(2019YFA0904501)the National Natural Science Foundation of China(Nos.81974122,81974116,82270906,82300980)China Postdoctoral Science Foundation(2023M732370).
文摘Dear Editor,Obesity is a major health issue with global prevalence and increases the risk of many metabolic diseases.Of particular con-cern is the increasing incidence of type 2 diabetes,the primary causes of which are obesity-driven insulin resistance in white adipose tissue(WAT),skeletal muscle,and liver,and decreased insulin secretion by pancreaticβ-cells[1].
基金supported by grants from the Shanghai Municipal Key Clinical Specialty, the National Natural Science Foundation of China(No. 8210087)the Interdisciplinary Program of Shanghai Jiao Tong University(No. YG2021QN105)
文摘Background: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM).Methods: In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm2.Results: Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P< 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595–0.866,P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (allP for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients.Conclusions: There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.
基金supported by the Shanghai Municipal Government Grants Award(No.GWIV-3)the Shanghai Health Policy Grant(No.2019HP49)+3 种基金the Shanghai Health Commission Grant(No.20194Y0141)the Shanghai Jiao Tong University Grant(No.CHDI-2018-A-05)the Shanghai Public Health Youth Award(No.GWV-10.2-YQ24)the Three-Year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System(No.GWV-10.1-XK05).
文摘This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the analysis.Profiles of risk factors and intermediate outcomes were determined.The patients had a mean age of 66.43±8.12(standard deviation(SD))years and a mean diabetes duration of 7.95±5.53(SD)years.The percentage of patients who achieved the target level for HbA_(1c)(<7.0%)was 48.6%.Patients who achieved the target levels for blood pressure(BP)<130/80 mmHg and low-density lipoprotein-cholesterol(LDL-c)<2.6 mmol/L reached 17.5%and 34.0%,respectively.A total of 3.8%achieved all three target levels,and the value increased to 6.8%with an adaptation of the BP target level(<140/90 mmHg)for those over 65 years.Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels:male,young age,short diabetes duration,low body mass index,macrovascular complications,no microvascular complications,prescribed with lipid-lowering medication,and no prescription of antihypertensive medication.In conclusion,nearly 50%and one-third of the patients with diabetes met the target levels for HbA_(1c)and LDL-c,respectively,with a low percentage achieving the BP target level.The percentage of patients who achieved all three target levels needs significant improvement.
基金supported by grants from the Shanghai Health and Family Planning Commission(Nos.20184Y0362,20204Y0431)the Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant Support(No.20161430)supported by the funding of retrospective studies from Shanghai Sixth People’s Hospital.
文摘Background: The potential impact of β cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between β cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes.Methods: This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on β cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of β cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models.Results: Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively (P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16-1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for β cell function (HOMA-β) were 1.00, 0.51, 0.60, and 0.53, respectively (P for trend = 0.068). When HOMA-β was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24-0.90) for each 1-unit increase in HOMA-β. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes.Conclusions: We demonstrated a significant association of β cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values.
文摘Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a multinational,multicenter,randomized,double-blind,treat-to-target,26-week,phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes(T2D).After an 8-week lead-in period during which basal insulin glargine or degludec was optimized,adults with T2D were randomized(2:1)to prandial URLi(n=395)or lispro(n=200).The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c(HbA_(1c))change from baseline to week 26.Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1-and 2-h PPG excursions during a mixed-meal tolerance test(MMTT)and HbA_(1c) change at week 26.URLi showed non-inferiority for Hb Achange at week 26 versus lispro(least-squares mean[LSM]difference,0.07%;95%confidence interval:-0.07,0.21).HbA_(1c) was reduced by 0.56%and 0.63%with URLi and lispro,respectively,with no significant treatment difference(P=0.321).URLi provided superior PPG excursion control versus lispro at1 h(LSM difference:-14.6 mg/d L,P<0.001)and 2 h(LSM difference:-21.8 mg/d L,P<0.001)as well as other time points(30–240 min)during the MMTT.Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro.The safety profiles were generally similar between treatment groups.In conclusion,URLi was superior to lispro for PPG control,with noninferiority in HbA_(1c) improvement,in adults with T2D.
基金This work was funded by the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(Nos.20161430 and 20172025)National Natural Science Foundation of China(Nos.81873646 and 81670790)Shanghai Municipal Key Clinical Specialty。
文摘Lifestyle interventions,including dietary adjustments and exercise,are important for obesity management.This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exercise is more effective in metabolism improvement.Forty-five eligible subjects were randomly divided into an LCD group(n=22)and an exercise group(EX,n=23).The subjects either adopted LCD(carbohydrate intake<50 g/day)or performed moderate-to-vigorous exercise(≥30 min/day)for 3 weeks.After the interventions,LCD led to a larger weight loss than EX(−3.56±0.37 kg vs.−1.24±0.39 kg,P<0.001),as well as a larger reduction in fat mass(−2.10±0.18 kg vs.−1.25±0.24 kg,P=0.007)and waist circumference(−5.25±0.52 cm vs.−3.45±0.38 cm,P=0.008).Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance.Triglycerides decreased in both two groups,whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group.Various glycemic parameters,including serum glycated albumin,mean sensor glucose,coefficient of variability(CV),and largest amplitude of glycemic excursions,substantially declined in the LCD group.Only CV slightly decreased after exercise.This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance.Compared with exercise,LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.
基金This study was supported by the Clinical Research Plan of SHDC(SHDC2020CR1017B)Shanghai Municipal Key Clinical Specialty,the National Natural Science Foundation of China(81670791)+2 种基金Municipal Natural Science Foundation of Shanghai(17ZR1421200)Shanghai Key Clinical Center for Metabolic Disease(2017ZZ01013)Clinical Retrospective Study of Shanghai Jiao Tong University Affiliated Sixth Peopled Hospital(YNHG201912 and YNHG202006).
文摘Obesity and its related complications comprise a serious public health problem worldwide,and obesity is increasing in China.Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications.The pathogenesis of obesity is complex and not yet fully understood.Here,we review the current efficacy and safety of metabolic surgery,as well as recent progress in mechanistic studies and surgical procedures in China.The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.
