Reportedly, the stress–hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population.
Methods
A total of 18 480 participants were included out of 82 091 from the NHANES 1999–2014 survey. The Kaplan–Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted.
Results
A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28–1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16–1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis.
Conclusions
The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.
{"title":"Association between the stress–hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999–2014","authors":"Shifeng Qiu, Xiaocong Liu, Li Lei, Hongbin Liang, Xue Li, Yutian Wang, Chen Yu, Xiaobo Li, Yongzhen Tang, Juefei Wu, Yuegang Wang, Daogang Zha, Xuewei Liu, Min Xiao, Jiancheng Xiu","doi":"10.1111/1753-0407.13567","DOIUrl":"10.1111/1753-0407.13567","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Reportedly, the stress–hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 18 480 participants were included out of 82 091 from the NHANES 1999–2014 survey. The Kaplan–Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank <i>p</i> < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28–1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16–1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bochra Zareini, Katrine Kold Sørensen, Ulrik Pedersen-Bjergaard, Emil Loldrup Fosbøl, Lars Køber, Christian Torp-Pedersen
<div> <section> <h3> Aim</h3> <p>To compare the cardiovascular preventive effect associated with glucagon-like-peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) according to the achieved target level of glycated hemoglobin (HbA1c).</p> </section> <section> <h3> Methods</h3> <p>We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP-1 RA or DPP-4i between 2007 and 2021. Patients were included 6 months after GLP-1 RA or DPP-4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP-1 RA users compared to DPP-4i users.</p> </section> <section> <h3> Results</h3> <p>The study included 13 634 GLP-1 RA users (median age 56.9, interquartile range [IQR]: 48.5–65.5; 53% males) and 39 839 DPP-4i users (median age 63.4, IQR: 54.6–71.8; 61% males). The number of GLP-1 RA and DPP-4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow-up of 5 years (IQR: 2.6–5.0), 954 GLP-1 RA users experienced the primary outcome compared to 7093 DPP-4i users. The 5-year risk (95% confidence interval [CI]) of the outcome associated with GLP1-RA versus DPP-4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2–12.3) versus 24.3% (22.7–25.8); HbA1c > 53 mmol/mol: 16.0% (14.3–17.6) versus 21.1% (20.3–21.9); missing HbA1c: 17.1% (15.7–18.5) versus 25.6% (24.9–26.3). The preventive effect associated with GLP-1 RA versus DPP-4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52–0.80); HbA1c > 53 mmol/mol: 0.92 (0.83–1.03); missing HbA1c: 0.92 (0.84–1.02) (<i>p</i> value for interaction <.001).</p> </section> <section> <h3> Conclusion</h3> <p>GLP-1 RA use was associated with a lower rate of major adverse cardiovascular outcomes. The association was stronger in patients achieving the target glycemic level and weaker in patients not achieving the target glycemic level, suggestive of an interaction between achieved HbA1c level and GLP-1 RA.</p>
{"title":"Glucagon-like-peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes in diabetes in relation to achieved glycemic control. A Danish nationwide study","authors":"Bochra Zareini, Katrine Kold Sørensen, Ulrik Pedersen-Bjergaard, Emil Loldrup Fosbøl, Lars Køber, Christian Torp-Pedersen","doi":"10.1111/1753-0407.13560","DOIUrl":"10.1111/1753-0407.13560","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To compare the cardiovascular preventive effect associated with glucagon-like-peptide-1 receptor agonists (GLP-1 RA) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) according to the achieved target level of glycated hemoglobin (HbA1c).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used retrospective Danish registries to include type 2 diabetes patients already in metformin treatment initiating GLP-1 RA or DPP-4i between 2007 and 2021. Patients were included 6 months after GLP-1 RA or DPP-4i initiation. The last available HbA1c measurement before inclusion was collected. The achieved HbA1c level was categorized according to a target level below or above 53 mmol/mol (7%). The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. We used a multivariable Cox proportional hazard model to estimate the effect of HbA1c levels on the outcome among GLP-1 RA users compared to DPP-4i users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 13 634 GLP-1 RA users (median age 56.9, interquartile range [IQR]: 48.5–65.5; 53% males) and 39 839 DPP-4i users (median age 63.4, IQR: 54.6–71.8; 61% males). The number of GLP-1 RA and DPP-4i users according to achieved HbA1c levels were as follows: HbA1c ≤ 53 mmol/mol (≤7.0%): 3026 (22%) versus 4824 (12%); HbA1c > 53 mmol/mol (>7.0%): 6577 (48%) versus 17 508 (44%); missing HbA1c: 4031 (30%) versus 17 507 (44%). During a median follow-up of 5 years (IQR: 2.6–5.0), 954 GLP-1 RA users experienced the primary outcome compared to 7093 DPP-4i users. The 5-year risk (95% confidence interval [CI]) of the outcome associated with GLP1-RA versus DPP-4i according to HbA1c categories was as follows: HbA1c ≤ 53 mmol/mol: 10.3% (8.2–12.3) versus 24.3% (22.7–25.8); HbA1c > 53 mmol/mol: 16.0% (14.3–17.6) versus 21.1% (20.3–21.9); missing HbA1c: 17.1% (15.7–18.5) versus 25.6% (24.9–26.3). The preventive effect associated with GLP-1 RA versus DPP-4i was significantly enhanced when achieving lower HbA1c levels: HbA1c ≤ 53 mmol/mol: 0.65 (0.52–0.80); HbA1c > 53 mmol/mol: 0.92 (0.83–1.03); missing HbA1c: 0.92 (0.84–1.02) (<i>p</i> value for interaction <.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GLP-1 RA use was associated with a lower rate of major adverse cardiovascular outcomes. The association was stronger in patients achieving the target glycemic level and weaker in patients not achieving the target glycemic level, suggestive of an interaction between achieved HbA1c level and GLP-1 RA.</p>\u0000 \u0000 ","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetes mellitus (DM) is a common chronic disease affecting humans globally. It is characterized by abnormally elevated blood glucose levels due to the failure of insulin production or reduction of insulin sensitivity and functionality. Insulin and glucagon-like peptide (GLP)-1 replenishment or improvement of insulin resistance are the two major strategies to treat diabetes. Recently, optogenetics that uses genetically encoded light-sensitive proteins to precisely control cell functions has been regarded as a novel therapeutic strategy for diabetes. Here, we summarize the latest development of optogenetics and its integration with synthetic biology approaches to produce light-responsive cells for insulin/GLP-1 production, amelioration of insulin resistance and neuromodulation of insulin secretion. In addition, we introduce the development of cell encapsulation and delivery methods and smart bioelectronic devices for the in vivo application of optogenetics-based cell therapy in diabetes. The remaining challenges for optogenetics-based cell therapy in the clinical translational study are also discussed.
{"title":"Optogenetic therapeutic strategies for diabetes mellitus","authors":"Xin Deng, Dandan Peng, Yuanfa Yao, Ke Huang, Jinling Wang, Zhihao Ma, Junfen Fu, Yingke Xu","doi":"10.1111/1753-0407.13557","DOIUrl":"10.1111/1753-0407.13557","url":null,"abstract":"<p>Diabetes mellitus (DM) is a common chronic disease affecting humans globally. It is characterized by abnormally elevated blood glucose levels due to the failure of insulin production or reduction of insulin sensitivity and functionality. Insulin and glucagon-like peptide (GLP)-1 replenishment or improvement of insulin resistance are the two major strategies to treat diabetes. Recently, optogenetics that uses genetically encoded light-sensitive proteins to precisely control cell functions has been regarded as a novel therapeutic strategy for diabetes. Here, we summarize the latest development of optogenetics and its integration with synthetic biology approaches to produce light-responsive cells for insulin/GLP-1 production, amelioration of insulin resistance and neuromodulation of insulin secretion. In addition, we introduce the development of cell encapsulation and delivery methods and smart bioelectronic devices for the in vivo application of optogenetics-based cell therapy in diabetes. The remaining challenges for optogenetics-based cell therapy in the clinical translational study are also discussed.</p><p>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
YunXia Wang, JiaJia Yang, Chun Wu, Yuqin Guo, Yuan Ding, Xiujuan Zou
Background
Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene14 (SNHG14) in DN were explored.
Methods
Streptozotocin (STZ)-induced DN mouse models and high glucose (HG)-treated human mesangial cells (MCs) were used to detect SNHG14 expression. SNHG14 silencing plasmids were applied to examine the function of SNHG14 on proliferation and fibrosis in HG-treated MCs. Potential targets of SNHG14 were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of SNHG14 in DN in vivo was detected by injection with adenoviral vector carrying sh-SNHG14 into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24-h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice.
Results
SNHG14 expression was elevated in the kidneys of DN mice and HG-treated MCs. SNHG14 silencing inhibited proliferation and fibrosis of HG-stimulated MCs. SNHG14 bound to miR-30e-5p to upregulate SOX4 expression. In rescue assays, SOX4 elevation diminished the effects of SNHG14 silencing in HG-treated MCs, and SOX4 silencing reversed the effects of SNHG14 overexpression. In in vivo studies, SNHG14 downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice.
Conclusions
SNHG14 silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG-stimulated MCs via the miR-30e-5p/SOX4 axis.
{"title":"LncRNA SNHG14 silencing attenuates the progression of diabetic nephropathy via the miR-30e-5p/SOX4 axis","authors":"YunXia Wang, JiaJia Yang, Chun Wu, Yuqin Guo, Yuan Ding, Xiujuan Zou","doi":"10.1111/1753-0407.13565","DOIUrl":"10.1111/1753-0407.13565","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA <i>small nucleolar RNA host gene</i> <i>14</i> (<i>SNHG14</i>) in DN were explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Streptozotocin (STZ)-induced DN mouse models and high glucose (HG)-treated human mesangial cells (MCs) were used to detect <i>SNHG14</i> expression. <i>SNHG14</i> silencing plasmids were applied to examine the function of <i>SNHG14</i> on proliferation and fibrosis in HG-treated MCs. Potential targets of <i>SNHG14</i> were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of <i>SNHG14</i> in DN in vivo was detected by injection with adenoviral vector carrying sh-<i>SNHG14</i> into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24-h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>SNHG14</i> expression was elevated in the kidneys of DN mice and HG-treated MCs. <i>SNHG14</i> silencing inhibited proliferation and fibrosis of HG-stimulated MCs. <i>SNHG14</i> bound to <i>miR-30e-5p</i> to upregulate <i>SOX4</i> expression. In rescue assays, <i>SOX4</i> elevation diminished the effects of <i>SNHG14</i> silencing in HG-treated MCs, and <i>SOX4</i> silencing reversed the effects of <i>SNHG14</i> overexpression. In in vivo studies, <i>SNHG14</i> downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>SNHG14</i> silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG-stimulated MCs via the <i>miR-30e-5p</i>/<i>SOX4</i> axis.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13565","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adesh Ranganna, Wenya Chen, Sean DeLacey, Juan Lado, Laura Levin, Anita Swamy, Monica E. Bianco
Background
Early identification and management of pediatric type 2 diabetes mellitus (T2DM) is crucial for improving long-term outcomes. This study aimed to assess if the severity of T2DM at presentation, inferred by the location of treatment initiation (inpatient or outpatient), influences long-term clinical outcomes.
Methods
A retrospective chart review was conducted on 116 pediatric T2DM patients. Data on treatment initiation location, initial and subsequent glycated hemoglobin (HbA1c) levels, prescribed insulin, and body mass index were collected from electronic medical records.
Results
Of the 116 patients, 69 were initially treated in an inpatient setting, and 47 received outpatient treatment. At treatment initiation, the inpatient group had significantly higher HbA1c levels compared to the outpatient group (p < .001), but 3 years after treatment initiation, no significant difference in HbA1c was observed between the two groups (p = .057). Prescribed insulin dosages were higher in the inpatient group at treatment initiation (p < .001) and remained higher after 3 years (p < 0.003) compared to the outpatient group.
Conclusions
Pediatric patients initially treated in an inpatient setting had poorer glycemic control and higher prescribed insulin dosing at baseline. After 3 years, there was no significant difference in HbA1c levels, but patients treated as inpatients continued to have higher prescribed insulin. These findings suggest that the severity of diabetes at initial presentation may affect long-term clinical outcomes in children with T2DM.
{"title":"Comparing long-term outcomes of children treated with new-onset type 2 diabetes in an outpatient versus inpatient setting: A retrospective chart review","authors":"Adesh Ranganna, Wenya Chen, Sean DeLacey, Juan Lado, Laura Levin, Anita Swamy, Monica E. Bianco","doi":"10.1111/1753-0407.13571","DOIUrl":"10.1111/1753-0407.13571","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early identification and management of pediatric type 2 diabetes mellitus (T2DM) is crucial for improving long-term outcomes. This study aimed to assess if the severity of T2DM at presentation, inferred by the location of treatment initiation (inpatient or outpatient), influences long-term clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective chart review was conducted on 116 pediatric T2DM patients. Data on treatment initiation location, initial and subsequent glycated hemoglobin (HbA1c) levels, prescribed insulin, and body mass index were collected from electronic medical records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 116 patients, 69 were initially treated in an inpatient setting, and 47 received outpatient treatment. At treatment initiation, the inpatient group had significantly higher HbA1c levels compared to the outpatient group (<i>p</i> < .001), but 3 years after treatment initiation, no significant difference in HbA1c was observed between the two groups (<i>p</i> = .057). Prescribed insulin dosages were higher in the inpatient group at treatment initiation (<i>p</i> < .001) and remained higher after 3 years (<i>p</i> < 0.003) compared to the outpatient group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pediatric patients initially treated in an inpatient setting had poorer glycemic control and higher prescribed insulin dosing at baseline. After 3 years, there was no significant difference in HbA1c levels, but patients treated as inpatients continued to have higher prescribed insulin. These findings suggest that the severity of diabetes at initial presentation may affect long-term clinical outcomes in children with T2DM.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non-Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown.
Methods
The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP-5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes.
Results
Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non-Asians: (weighted mean difference [WMD], −0.59, 95% CI, −0.73 to −0.45, p < .01) vs (WMD, −0.29, 95% CI, −0.32 to −0.27, p < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non-Asians (p > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, −5.12, 95% CI, −5.84 to −4.41, p < .01) compared to non-Asians (WMD, −3.64, 95% CI, −4.38 to −2.89, p < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non-Asians (p < .01).
Conclusions
Nonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non-Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%.
{"title":"Renal effects and safety between Asian and non-Asian chronic kidney disease and type 2 diabetes treated with nonsteroidal mineralocorticoid antagonists","authors":"Xiaoming Xu, Jing Feng, Yuying Cui, Pingjiang Li, Jianjun Dong, Lin Liao","doi":"10.1111/1753-0407.13566","DOIUrl":"https://doi.org/10.1111/1753-0407.13566","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non-Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP-5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non-Asians: (weighted mean difference [WMD], −0.59, 95% CI, −0.73 to −0.45, <i>p</i> < .01) vs (WMD, −0.29, 95% CI, −0.32 to −0.27, <i>p</i> < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non-Asians (<i>p</i> > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, −5.12, 95% CI, −5.84 to −4.41, <i>p</i> < .01) compared to non-Asians (WMD, −3.64, 95% CI, −4.38 to −2.89, <i>p</i> < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non-Asians (<i>p</i> < .01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Nonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non-Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140952971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous studies have shown that sarcopenic obesity (SO) was associated with nonalcoholic fatty liver disease (NAFLD). However, research is limited in the context of the NAFLD renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) defined by updated diagnostic criteria. The aim of this study was to use the index skeletal muscle mass to visceral fat area ratio (SVR) to describe SO in a large and representative US population (National Health and Nutrition Examination Survey 2017–2018) of adults and investigate their association with MASLD.
Methods
A total of 2087 individuals were included in the analysis. SVR was calculated according to the measurement of dual-energy x-ray absorptiometry and MASLD was diagnosed with controlled attenuation parameter scores and cardiometabolic risk factors. SVR was divided into tertiles. Logistic regression adjusted for confounders was used to evaluate the association between SVR and MASLD. Several sensitivity analyses were performed to test the robustness of our findings.
Results
In a multivariate logistic regression analysis, a significant association between SVR and MASLD was shown (odds ratio [OR]: 3.11, 95% confidence interval [CI]: 1.31–7.39, p = .010 for middle levels of SVR; OR: 3.82, 95% CI: 1.45–10.08, p = .007 for lowest levels of SVR). The sensitivity analyses confirmed that the association was robust.
Conclusion
Our findings imply that decreased SVR is linked to MASLD.
背景和目的：以往的研究表明，肌肉疏松性肥胖（SO）与非酒精性脂肪肝（NAFLD）有关。然而，根据最新诊断标准定义的非酒精性脂肪肝更名为代谢功能障碍相关性脂肪肝（MASLD），在此背景下的研究却很有限。本研究旨在使用骨骼肌质量与内脏脂肪面积比（SVR）指数来描述具有代表性的大规模美国成年人群（2017-2018 年全国健康与营养调查）中的 SO，并调查其与 MASLD 的关联：共有2087人被纳入分析。SVR 根据双能 X 射线吸收测量法的测量结果进行计算，MASLD 根据受控衰减参数评分和心脏代谢风险因素进行诊断。SVR 被分为三等分。采用调整混杂因素后的逻辑回归评估 SVR 与 MASLD 之间的关系。我们还进行了多项敏感性分析，以检验研究结果的稳健性：结果：在多变量逻辑回归分析中，SVR 与 MASLD 之间存在显著关联（几率比 [OR]：3.11，95% 置信区间 [CI]：1.31-7.39, p = .010 for middle levels of SVR; OR：3.82，95% 置信区间：1.45-10.08，P = .007）。敏感性分析证实这种关联是稳健的：我们的研究结果表明，SVR 的下降与 MASLD 有关。
{"title":"Association between the skeletal muscle mass to visceral fat area ratio and metabolic dysfunction-associated fatty liver disease: A cross-sectional study of NHANES 2017–2018","authors":"Zhiliang Mai, Yinfei Chen, Hua Mao, Lisheng Wang","doi":"10.1111/1753-0407.13569","DOIUrl":"10.1111/1753-0407.13569","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Previous studies have shown that sarcopenic obesity (SO) was associated with nonalcoholic fatty liver disease (NAFLD). However, research is limited in the context of the NAFLD renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) defined by updated diagnostic criteria. The aim of this study was to use the index skeletal muscle mass to visceral fat area ratio (SVR) to describe SO in a large and representative US population (National Health and Nutrition Examination Survey 2017–2018) of adults and investigate their association with MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 2087 individuals were included in the analysis. SVR was calculated according to the measurement of dual-energy x-ray absorptiometry and MASLD was diagnosed with controlled attenuation parameter scores and cardiometabolic risk factors. SVR was divided into tertiles. Logistic regression adjusted for confounders was used to evaluate the association between SVR and MASLD. Several sensitivity analyses were performed to test the robustness of our findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In a multivariate logistic regression analysis, a significant association between SVR and MASLD was shown (odds ratio [OR]: 3.11, 95% confidence interval [CI]: 1.31–7.39, <i>p</i> = .010 for middle levels of SVR; OR: 3.82, 95% CI: 1.45–10.08, <i>p</i> = .007 for lowest levels of SVR). The sensitivity analyses confirmed that the association was robust.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings imply that decreased SVR is linked to MASLD.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherine De la Torre, Minkyo Song, Sarah Krull Abe, Md. Shafiur Rahman, Md. Rashedul Islam, Eiko Saito, Sukhong Min, Dan Huang, Yu Chen, Prakash C. Gupta, Norie Sawada, Akiko Tamakoshi, Xiao-Ou Shu, Wanqing Wen, Ritsu Sakata, Jeongseon Kim, Chisato Nagata, Hidemi Ito, Sue K. Park, Myung-Hee Shin, Mangesh S. Pednekar, Shoichiro Tsugane, Takashi Kimura, Yu-Tang Gao, Hui Cai, Keiko Wada, Isao Oze, Aesun Shin, Yoon-Ok Ahn, Habibul Ahsan, Paolo Boffetta, Kee Seng Chia, Keitaro Matsuo, You-Lin Qiao, Nathaniel Rothman, Wei Zheng, Manami Inoue, Daehee Kang
Background
Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes.
Methods
A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses.
Results
Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03–1.28) but attenuated after a 2-year time lag.
Conclusion
Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.
背景：有证据表明，糖尿病与胃癌风险之间可能存在联系，但研究结果仍不确定，对亚洲人群的研究也很有限。我们旨在按解剖学和组织学亚型评估糖尿病和糖尿病持续时间对胃癌发病的总体影响：我们利用亚洲队列联合会（Asia Cohort Consortium）的 12 项前瞻性研究进行了汇总分析。在558 981名参与者（中位年龄为52岁）中，经过中位14.9年和10.5年的随访，分别有8556人发生原发性胃癌，8058人死于胃癌。研究人员使用考克斯比例危险回归模型估算了特定研究的危险比（HRs）和95%置信区间（CIs），并使用随机效应荟萃分析进行了汇总：糖尿病与总体胃癌发病率增加有关（HR 1.15，95% CI 1.06-1.25）。不同性别（女性 vs 男性：HR 1.31，95% CI 1.07-1.60 vs 1.12，1.01-1.23）、解剖亚部位（非贲门 vs 贲门：1.14，1.02-1.28 vs 1.17，0.77-1.78）和组织学亚型（肠型 vs 弥漫型：1.22，1.02-1.46 vs 1.00，0.62-1.61）的风险相关性差异不大。在糖尿病确诊后的头十年，胃癌风险明显增加（HR 4.70，95% CI 3.77-5.86），并随着时间的推移而降低（非线性 p 结论：糖尿病与胃癌风险增加有关：无论性别、解剖部位或胃癌亚型如何，糖尿病都与胃癌发病率增加有关。在糖尿病确诊后的头十年，患胃癌的风险尤其高。
{"title":"Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants","authors":"Katherine De la Torre, Minkyo Song, Sarah Krull Abe, Md. Shafiur Rahman, Md. Rashedul Islam, Eiko Saito, Sukhong Min, Dan Huang, Yu Chen, Prakash C. Gupta, Norie Sawada, Akiko Tamakoshi, Xiao-Ou Shu, Wanqing Wen, Ritsu Sakata, Jeongseon Kim, Chisato Nagata, Hidemi Ito, Sue K. Park, Myung-Hee Shin, Mangesh S. Pednekar, Shoichiro Tsugane, Takashi Kimura, Yu-Tang Gao, Hui Cai, Keiko Wada, Isao Oze, Aesun Shin, Yoon-Ok Ahn, Habibul Ahsan, Paolo Boffetta, Kee Seng Chia, Keitaro Matsuo, You-Lin Qiao, Nathaniel Rothman, Wei Zheng, Manami Inoue, Daehee Kang","doi":"10.1111/1753-0407.13561","DOIUrl":"10.1111/1753-0407.13561","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear <i>p</i> < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03–1.28) but attenuated after a 2-year time lag.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13561","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>The worldwide annual incidence of type 1 diabetes (T1D) among children and adolescents is approximately 200 000 persons, half age ≤15,<span><sup>1</sup></span> with an additional 330 000 over age 20 developing T1D annually. The worldwide prevalence of T1D 8 760 000, more than 7 000 000 of whom are over age 20.<span><sup>2</sup></span> We now recognize that there are a substantial number of persons without overt diabetes who may nevertheless be considered to have T1D: those with normal blood glucose but evidence of an autoimmune response to islet autoantigens, considered to have stage 1 T1D; those with abnormal blood glucose in the pre-diabetes range as well as islet autoantibodies, considered to have stage 2; those with clinical diabetes but still evidence of β-cell reserve, Stage 3; and those with established T1D and progressively declining β-cell reserve, stage 4.<span><sup>3</sup></span> Although we know of the existence of stages 1 and 2, it has not been easy to determine their prevalence. In a study of 153 854 youths age 2–10 in Bavaria, Germany, 153 313 screened negative for islet antibodies, of whom 18 developed T1D, 541 screened positive, of whom 447 had multiple autoantibodies; 293 were in stage 1, 61 of whom progressed to Stage 3, 30 were in stage 2, of whom 16 progressed to Stage 3, 14 were Stage 3, 83 declined staging, of whom 10 progressed to Stage 3. Thus, 0.35% of the screened children were antibody-positive, of whom 101 (less than 20%) developed T1D during the 2-3 year period of observation.<span><sup>4</sup></span> As the short-term disease progression risk is low, prolonged observation of a relatively large number of persons from a relatively rare population will be required to fully characterize stages 1 and 2 of T1D; further, the approaches used in assessing potential treatment approaches are hampered by the poor reproducibility of the oral glucose tolerance test, by the effect of variable degrees of insulin sensitivity on insulin secretion and hence on C-peptide levels, and by the benefit of continuous glucose monitoring-guided closed-loop insulin pump systems in controlling glycosylated hemoglobin (HbA1c) and in minimizing hypoglycemia.<span><sup>5</sup></span></p><p>Most studies of the pathogenesis of T1D suggest that β-cell destruction is mediated by T lymphocytes, with the role of islet cell antibodies in the process uncertain. For those not having diabetes, the effects of autoreactive effector T cells are counterbalanced by regulatory T cells, only with those having an expanded or resistant population of effector T cells or impaired regulatory T cells going on to develop T1D.<span><sup>6</sup></span></p><p>A number of randomized controlled trials have been carried out to assess potential approaches to T1D prevention in stages 1 and 2; one of two diet-based interventions with avoidance of cow's milk suggested benefit, one trial was negative with avoidance of gluten exposure, two were negative with administration of nic
10 Janus 激酶（JAK）抑制剂作用于这些酶的三磷酸腺苷结合位点，抑制一系列信号传导途径，从而产生免疫调节效应，这些效应已在恶性肿瘤、类风湿性关节炎等炎症性疾病以及移植物抗宿主疾病中显示出疗效11；一项关于 JAK 抑制剂巴利昔尼的研究发现，60 名 T1D 患者在发病 100 天内，刺激 C 肽峰值≥0.2 发现，在接受安慰剂治疗的 30 位患者中，95% 的患者 C 肽得以保留，而 79% 的患者 C 肽得以保留，同时胰岛素需求量减少，HbA1c 下降（尽管基线较低）。12 同样，这也不是一种完全良性的治疗方法，产品信息中提到了潜在的不良反应，包括 "严重细菌、真菌、病毒和机会性感染导致住院或死亡的风险......在治疗期间监测所有患者是否有活动性结核病，即使是最初潜伏结核病检测阴性的患者......全因死亡率较高......恶性肿瘤......MACE......[和]血栓形成。"13 利妥昔单抗是一种针对 CD20（一种存在于 B 淋巴细胞上的蛋白质）的单克隆抗体，81 名 T1D 患者在 100 天内发病，抗胰岛抗体阳性，刺激 C 肽峰值≥0.2，30 个月内 HbA1c 和胰岛素剂量需求降低。同样，在产品信息的 "黑框 "中列举了一些潜在的副作用："致命的输液相关反应、严重的粘膜反应、乙型肝炎病毒再激活和进行性多灶性白质脑病 "15。"15 对多种潜在药物的比较表明，特普利珠单抗和抗胸腺细胞球蛋白能最大程度地保留 C 肽，而阿来非普特（一种干扰 CD2 介导的成本刺激并专门针对记忆 T 细胞的融合蛋白）、阿巴他赛普（一种干扰 T 淋巴细胞完全活化所需的协同刺激的融合蛋白）和利妥昔单抗的效果较差。目前正在考虑可能毒性较低的方法。基于抗原特异性表位的免疫疗法可能会恢复抗原特异性耐受17、18。免疫检查点调节剂19、基于嵌合抗原受体的细胞疗法20 和其他改变疾病免疫疗法的新方法21 都在研究之中，其中一些可能被证明是安全有效的。在我们早些时候关于使用促增殖剂治疗早期 T1D 的评论中，我们注意到一项初步研究，钙通道阻滞剂维拉帕米有可能抑制硫氧还蛋白相互作用蛋白，从而减少 β 细胞的葡萄糖毒性和细胞凋亡22。随后的一项对照试验将 88 名 7-17 岁新诊断为 T1D 的儿童和青少年随机分组，分别服用维拉帕米和安慰剂；52 周后，服用维拉帕米的患者的平均 C 肽比服用安慰剂的患者高 30%，95% 的治疗患者与 71% 的安慰剂患者相比，刺激 C 肽≥0.2 pmol/mL。值得注意的是，Tzield（特普利单抗）两个 12vial 疗程的费用为 332400 美元，而在美国，维拉帕米 30 天的用量为 5-40 美元，一年的费用在 60-480 美元之间。
{"title":"Can type 1 diabetes be prevented or reversed?","authors":"Zachary Bloomgarden","doi":"10.1111/1753-0407.13572","DOIUrl":"10.1111/1753-0407.13572","url":null,"abstract":"<p>The worldwide annual incidence of type 1 diabetes (T1D) among children and adolescents is approximately 200 000 persons, half age ≤15,<span><sup>1</sup></span> with an additional 330 000 over age 20 developing T1D annually. The worldwide prevalence of T1D 8 760 000, more than 7 000 000 of whom are over age 20.<span><sup>2</sup></span> We now recognize that there are a substantial number of persons without overt diabetes who may nevertheless be considered to have T1D: those with normal blood glucose but evidence of an autoimmune response to islet autoantigens, considered to have stage 1 T1D; those with abnormal blood glucose in the pre-diabetes range as well as islet autoantibodies, considered to have stage 2; those with clinical diabetes but still evidence of β-cell reserve, Stage 3; and those with established T1D and progressively declining β-cell reserve, stage 4.<span><sup>3</sup></span> Although we know of the existence of stages 1 and 2, it has not been easy to determine their prevalence. In a study of 153 854 youths age 2–10 in Bavaria, Germany, 153 313 screened negative for islet antibodies, of whom 18 developed T1D, 541 screened positive, of whom 447 had multiple autoantibodies; 293 were in stage 1, 61 of whom progressed to Stage 3, 30 were in stage 2, of whom 16 progressed to Stage 3, 14 were Stage 3, 83 declined staging, of whom 10 progressed to Stage 3. Thus, 0.35% of the screened children were antibody-positive, of whom 101 (less than 20%) developed T1D during the 2-3 year period of observation.<span><sup>4</sup></span> As the short-term disease progression risk is low, prolonged observation of a relatively large number of persons from a relatively rare population will be required to fully characterize stages 1 and 2 of T1D; further, the approaches used in assessing potential treatment approaches are hampered by the poor reproducibility of the oral glucose tolerance test, by the effect of variable degrees of insulin sensitivity on insulin secretion and hence on C-peptide levels, and by the benefit of continuous glucose monitoring-guided closed-loop insulin pump systems in controlling glycosylated hemoglobin (HbA1c) and in minimizing hypoglycemia.<span><sup>5</sup></span></p><p>Most studies of the pathogenesis of T1D suggest that β-cell destruction is mediated by T lymphocytes, with the role of islet cell antibodies in the process uncertain. For those not having diabetes, the effects of autoreactive effector T cells are counterbalanced by regulatory T cells, only with those having an expanded or resistant population of effector T cells or impaired regulatory T cells going on to develop T1D.<span><sup>6</sup></span></p><p>A number of randomized controlled trials have been carried out to assess potential approaches to T1D prevention in stages 1 and 2; one of two diet-based interventions with avoidance of cow's milk suggested benefit, one trial was negative with avoidance of gluten exposure, two were negative with administration of nic","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13572","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sizhe Wang, Guo Ruirui, Xiaotong Li, Fengdan Wang, Zibo Wu, Yan Liu, Yibo Dong, Bo Li
Background
The association between macronutrient intake and diabetes is unclear. We used data from the China Health and Nutrition Survey to explore the association between macronutrient intake trajectories and diabetes risk in this study.
Methods
We included 6755 participants who did not have diabetes at baseline and participated in at least three surveys. The energy supply ratio of carbohydrate, protein, and fat was further calculated from dietary data; different macronutrient trajectories were determined using multitrajectory models; and multiple Cox regression models were used to evaluate the association between these trajectories and diabetes.
Results
We found three multitrajectories: decreased low carbohydrate-increased moderate protein-increased high fat (DLC-IMP-IHF), decreased high carbohydrate-moderate protein-increased low fat (DHC-MP-ILF), and balanced-macronutrients (BM). Compared to the BM trajectory, DHC-MP-ILF trajectories were significantly associated with increased risk of diabetes (hazard ratio [HR]: 3.228, 95% confidence interval [CI]: 1.571–6.632), whereas no association between DLC-IMP-IHF trajectories and diabetes was found in our study (HR: 0.699, 95% CI: 0.351–1.392).
Conclusions
The downward trend of high carbohydrate and the increasing trend of low fat increased the risk of diabetes in Chinese adults.
{"title":"The association between multiple trajectories of macronutrient intake and the risk of new-onset diabetes in Chinese adults","authors":"Sizhe Wang, Guo Ruirui, Xiaotong Li, Fengdan Wang, Zibo Wu, Yan Liu, Yibo Dong, Bo Li","doi":"10.1111/1753-0407.13555","DOIUrl":"10.1111/1753-0407.13555","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The association between macronutrient intake and diabetes is unclear. We used data from the China Health and Nutrition Survey to explore the association between macronutrient intake trajectories and diabetes risk in this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 6755 participants who did not have diabetes at baseline and participated in at least three surveys. The energy supply ratio of carbohydrate, protein, and fat was further calculated from dietary data; different macronutrient trajectories were determined using multitrajectory models; and multiple Cox regression models were used to evaluate the association between these trajectories and diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found three multitrajectories: decreased low carbohydrate-increased moderate protein-increased high fat (DLC-IMP-IHF), decreased high carbohydrate-moderate protein-increased low fat (DHC-MP-ILF), and balanced-macronutrients (BM). Compared to the BM trajectory, DHC-MP-ILF trajectories were significantly associated with increased risk of diabetes (hazard ratio [HR]: 3.228, 95% confidence interval [CI]: 1.571–6.632), whereas no association between DLC-IMP-IHF trajectories and diabetes was found in our study (HR: 0.699, 95% CI: 0.351–1.392).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The downward trend of high carbohydrate and the increasing trend of low fat increased the risk of diabetes in Chinese adults.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13555","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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