Constipation is a common complication in type 2 diabetes mellitus (T2DM), yet its impact on mortality remains unclear. This study aimed to investigate the association between constipation and all-cause mortality in patients with T2DM.
Methods
We conducted a retrospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2010. Mortality outcomes were ascertained through linkage to National Death Index records until December 31, 2019. The association between constipation and all-cause mortality was assessed using weighted Cox proportional hazards regression models. Kaplan–Meier curves were then employed to visualize survival probabilities. Effect modification was explored through stratified analyses and interaction tests.
Results
Of 1,339 participants with T2DM, 146 (10.90%) reported constipation. During a median follow-up of 10.75 years, 411 deaths occurred (57 in the constipation group, 354 in the non-constipation group). Fully adjusted weighted Cox regression analysis revealed that constipation was associated with increased all-cause mortality (HR 1.50, 95% CI 1.01–2.22, P = 0.04). Kaplan–Meier analysis demonstrated a significantly lower survival probability in patients with constipation (log-rank P < 0.05). Stratified analyses and interaction tests corroborated these findings across various subgroups.
Conclusions
Constipation is associated with elevated all-cause mortality risk in T2DM patients. These findings suggest that constipation management may be an important consideration in improving long-term outcomes for individuals with T2DM.
背景：便秘是2型糖尿病（T2DM）的常见并发症，但其对死亡率的影响尚不清楚。本研究旨在探讨T2DM患者便秘与全因死亡率之间的关系。方法：采用2005-2010年国家健康与营养检查调查（NHANES）的数据进行回顾性队列研究。通过与截至2019年12月31日的国家死亡指数记录的联系来确定死亡率结果。使用加权Cox比例风险回归模型评估便秘与全因死亡率之间的关系。然后使用Kaplan-Meier曲线来可视化生存概率。通过分层分析和交互作用试验，探讨效应修正。结果：1339名T2DM患者中，146名（10.90%）报告便秘。在中位10.75年的随访期间，411人死亡（便秘组57人，非便秘组354人）。全校正加权Cox回归分析显示，便秘与全因死亡率增加相关（HR 1.50, 95% CI 1.01-2.22, P = 0.04）。Kaplan-Meier分析显示便秘患者的生存率显著降低（log-rank P）。结论：便秘与T2DM患者全因死亡风险升高相关。这些发现表明，便秘管理可能是改善T2DM患者长期预后的重要考虑因素。
{"title":"Association of constipation with all-cause mortality among individuals with type 2 diabetes: A retrospective cohort study","authors":"Xianhua Li, Haibin Wen, Jing Ke, Dong Zhao","doi":"10.1111/jdi.14375","DOIUrl":"10.1111/jdi.14375","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Constipation is a common complication in type 2 diabetes mellitus (T2DM), yet its impact on mortality remains unclear. This study aimed to investigate the association between constipation and all-cause mortality in patients with T2DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2010. Mortality outcomes were ascertained through linkage to National Death Index records until December 31, 2019. The association between constipation and all-cause mortality was assessed using weighted Cox proportional hazards regression models. Kaplan–Meier curves were then employed to visualize survival probabilities. Effect modification was explored through stratified analyses and interaction tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 1,339 participants with T2DM, 146 (10.90%) reported constipation. During a median follow-up of 10.75 years, 411 deaths occurred (57 in the constipation group, 354 in the non-constipation group). Fully adjusted weighted Cox regression analysis revealed that constipation was associated with increased all-cause mortality (HR 1.50, 95% CI 1.01–2.22, <i>P</i> = 0.04). Kaplan–Meier analysis demonstrated a significantly lower survival probability in patients with constipation (log-rank <i>P</i> < 0.05). Stratified analyses and interaction tests corroborated these findings across various subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Constipation is associated with elevated all-cause mortality risk in T2DM patients. These findings suggest that constipation management may be an important consideration in improving long-term outcomes for individuals with T2DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"501-509"},"PeriodicalIF":3.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiaoli Cui, Zhenming Zhang, Lang Qin, Zhaolin Teng, Zhihong Wang, Wei Wu, Linling Fan, Jing Su, Yexuan Hao, Ji Qin, Li Zhang, Qi Wang, Yuan Zhuang, Hangping Zheng, Shuo Zhang, Xiang Geng, Lei Zhu, Yijian Chen, Bin Lu, Yiming Li, Xiaoming Zhu
Aims/Introduction
Diabetic foot ulcer (DFU) is a prevalent complication of diabetes characterized by heightened inflammation and impaired wound-healing processes. Interleukin-37 (IL-37) is a natural suppressor of innate inflammation. Here, we aim to investigate the potential of IL-37 in enhancing the healing process of diabetic wounds.
Materials and Methods
The skin samples of DFU and non-diabetic patients during foot and ankle orthopedic surgery were collected. The IL-37 transgenic mice (IL-37Tg) were created using CRISPR/Cas-mediated genome engineering. Mice were administered streptozotocin (STZ, 150 mg/kg) to induce a diabetic model. After 4 weeks, an equidistant full-thickness excisional wound measuring 8 mm was created on the central back of each mouse and allowed to heal naturally. Body weight and blood glucose levels were measured weekly. The wound area was measured, and skin samples were collected on Day 10 for further Quantitative polymerase chain reaction (qPCR) and WB detection and RNA sequencing analysis.
Results
The proinflammation cytokines such as TNF-α and IL-1β and the MAPK signaling pathway were significantly increased in the wound margin of DFU patients. Compared with diabetic mice, diabetic IL-37Tg mice showed a significantly accelerated healing process. The enriched signaling pathways in RNA sequencing included cytokine–cytokine receptor interaction, TNF signaling pathway, and NOD-like receptor signaling pathway. Through QPCR and WB detection, we found that IL-37 could inhibit the activated MAPK and NOD-like signaling pathway, reducing TNF-α, IL-1β, and NLRP3 expression in the diabetic wound.
Conclusions
IL-37 promotes skin wound healing in diabetic mice, providing a new possible target for treating diabetic wounds.
{"title":"Interleukin-37 promotes wound healing in diabetic mice by inhibiting the MAPK/NLRP3 pathway","authors":"Qiaoli Cui, Zhenming Zhang, Lang Qin, Zhaolin Teng, Zhihong Wang, Wei Wu, Linling Fan, Jing Su, Yexuan Hao, Ji Qin, Li Zhang, Qi Wang, Yuan Zhuang, Hangping Zheng, Shuo Zhang, Xiang Geng, Lei Zhu, Yijian Chen, Bin Lu, Yiming Li, Xiaoming Zhu","doi":"10.1111/jdi.14389","DOIUrl":"10.1111/jdi.14389","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Diabetic foot ulcer (DFU) is a prevalent complication of diabetes characterized by heightened inflammation and impaired wound-healing processes. Interleukin-37 (IL-37) is a natural suppressor of innate inflammation. Here, we aim to investigate the potential of IL-37 in enhancing the healing process of diabetic wounds.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>The skin samples of DFU and non-diabetic patients during foot and ankle orthopedic surgery were collected. The IL-37 transgenic mice (IL-37Tg) were created using CRISPR/Cas-mediated genome engineering. Mice were administered streptozotocin (STZ, 150 mg/kg) to induce a diabetic model. After 4 weeks, an equidistant full-thickness excisional wound measuring 8 mm was created on the central back of each mouse and allowed to heal naturally. Body weight and blood glucose levels were measured weekly. The wound area was measured, and skin samples were collected on Day 10 for further Quantitative polymerase chain reaction (qPCR) and WB detection and RNA sequencing analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proinflammation cytokines such as TNF-α and IL-1β and the MAPK signaling pathway were significantly increased in the wound margin of DFU patients. Compared with diabetic mice, diabetic IL-37Tg mice showed a significantly accelerated healing process. The enriched signaling pathways in RNA sequencing included cytokine–cytokine receptor interaction, TNF signaling pathway, and NOD-like receptor signaling pathway. Through QPCR and WB detection, we found that IL-37 could inhibit the activated MAPK and NOD-like signaling pathway, reducing TNF-α, IL-1β, and NLRP3 expression in the diabetic wound.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IL-37 promotes skin wound healing in diabetic mice, providing a new possible target for treating diabetic wounds.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"405-413"},"PeriodicalIF":3.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Obstructive sleep apnea (OSA) is characterized by a complete or partial obstruction of the upper airway, along with hypoxemia, microarousals, and sleep fragmentation. Compelling evidence has clarified a bidirectional correlation between OSA and diabetes mellitus (DM). This paper was to assess the link between OSA and DM via meta-analysis, consisting of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).
Materials and Methods
Four databases (PubMed, Cochrane Library, Embase, and CNKI) were screened from inception to March 2024 for observational studies of OSA and DM, including case–control studies and cohort studies. Bidirectional associations between OSA and DM were analyzed, consisting of T1DM and T2DM. Random-effect models were employed to determine the pooled odds ratio (OR) and 95% confidence intervals (CIs) to compare prevalence. Traditional subgroup analyses were implemented. Review Manager 5.3 and Stata 16.0 were utilized for data analyses.
Results
Thirty-five studies were enrolled, including 12 prospective cohort studies, 4 retrospective cohort studies, and 19 case–control studies. DM prevalence was notably higher in OSA patients than in non-OSA patients (OR: 2.29, 95% CI: 1.93–2.72), and OSA prevalence was notably higher in DM patients than in non-DM patients (OR: 2.12, 95% CI: 1.73–2.60). Subgroup analysis uncovered that DM prevalence in the OSA population was more significant in the group <50 years (OR: 3.28, 95% CI: 2.20–4.89) and slightly decreased in the group >50 years (OR: 1.82, 95% CI: 1.38–2.40).
Conclusions
The meta-analysis reveals a bidirectional link between OSA and DM.
{"title":"Association between obstructive sleep apnea syndrome and type1/type2 diabetes mellitus: A systematic review and meta-analysis","authors":"Huiling Huang, Zhang Chen","doi":"10.1111/jdi.14354","DOIUrl":"10.1111/jdi.14354","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Obstructive sleep apnea (OSA) is characterized by a complete or partial obstruction of the upper airway, along with hypoxemia, microarousals, and sleep fragmentation. Compelling evidence has clarified a bidirectional correlation between OSA and diabetes mellitus (DM). This paper was to assess the link between OSA and DM via meta-analysis, consisting of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Four databases (PubMed, Cochrane Library, Embase, and CNKI) were screened from inception to March 2024 for observational studies of OSA and DM, including case–control studies and cohort studies. Bidirectional associations between OSA and DM were analyzed, consisting of T1DM and T2DM. Random-effect models were employed to determine the pooled odds ratio (OR) and 95% confidence intervals (CIs) to compare prevalence. Traditional subgroup analyses were implemented. Review Manager 5.3 and Stata 16.0 were utilized for data analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-five studies were enrolled, including 12 prospective cohort studies, 4 retrospective cohort studies, and 19 case–control studies. DM prevalence was notably higher in OSA patients than in non-OSA patients (OR: 2.29, 95% CI: 1.93–2.72), and OSA prevalence was notably higher in DM patients than in non-DM patients (OR: 2.12, 95% CI: 1.73–2.60). Subgroup analysis uncovered that DM prevalence in the OSA population was more significant in the group <50 years (OR: 3.28, 95% CI: 2.20–4.89) and slightly decreased in the group >50 years (OR: 1.82, 95% CI: 1.38–2.40).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The meta-analysis reveals a bidirectional link between OSA and DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"521-534"},"PeriodicalIF":3.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ye Feng, Xi Jin, Jing Zhu, Meng Yuan, Liang Zhu, Dan Ye, Yuqing Shen
Aim and Introduction
Diabetes and prediabetes pose significant global public health challenges. Sex steroids, particularly testosterone and estradiol, play crucial roles in various metabolic processes. This study investigates the relationship between sex hormone levels and long-term mortality in adults with prediabetes and diabetes, as well as those without glucose intolerance.
Material and Methods
This retrospective cohort study utilized data from the NHANES 2013–2016, including adults aged 50–79 across prediabetic, diabetic, and non-diabetic groups. Serum testosterone, estradiol, and their ratios (T/E) were analyzed. The primary outcomes were all-cause mortality and CVD mortality tracked until December 2019. Cox regression models estimated the associations between hormone levels and mortality risks.
Results
The study included 3,665 participants (male: 2,140; female: 1,775). In males with prediabetes, higher estradiol (adjusted hazard ratio [aHR] = 0.17, 95% confidence interval [CI]: 0.07–0.43) or testosterone (aHR = 0.39, 95% CI: 0.31–0.50) was significantly associated with lower risk of all-cause mortality. Higher estradiol (aHR = 0.12, 95% CI: 0.04–0.32) or testosterone (aHR = 0.36, 95% CI: 0.27–0.48) was significantly associated with lower CVD mortality risk. In females with diabetes, there was a significant association between higher estradiol levels (aHR = 0.22, 95% CI: 0.06–0.83) or T/E ratio (aHR = 0.18, 95% CI: 0.04–0.73) with a reduced all-cause mortality risk.
Conclusions
This study identifies some novel associations between estradiol, testosterone, and their ratios with long-term mortality in men and women across different glycemic statuses. These findings suggest a potential protective role of sex hormones in individuals with altered glucose metabolism, with gender difference, warranting further investigation.
{"title":"Association between endogenous estradiol, testosterone, and long-term mortality in adults with prediabetes and diabetes: Evidence from NHANES database","authors":"Ye Feng, Xi Jin, Jing Zhu, Meng Yuan, Liang Zhu, Dan Ye, Yuqing Shen","doi":"10.1111/jdi.14367","DOIUrl":"10.1111/jdi.14367","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim and Introduction</h3>\u0000 \u0000 <p>Diabetes and prediabetes pose significant global public health challenges. Sex steroids, particularly testosterone and estradiol, play crucial roles in various metabolic processes. This study investigates the relationship between sex hormone levels and long-term mortality in adults with prediabetes and diabetes, as well as those without glucose intolerance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>This retrospective cohort study utilized data from the NHANES 2013–2016, including adults aged 50–79 across prediabetic, diabetic, and non-diabetic groups. Serum testosterone, estradiol, and their ratios (T/E) were analyzed. The primary outcomes were all-cause mortality and CVD mortality tracked until December 2019. Cox regression models estimated the associations between hormone levels and mortality risks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 3,665 participants (male: 2,140; female: 1,775). In males with prediabetes, higher estradiol (adjusted hazard ratio [aHR] = 0.17, 95% confidence interval [CI]: 0.07–0.43) or testosterone (aHR = 0.39, 95% CI: 0.31–0.50) was significantly associated with lower risk of all-cause mortality. Higher estradiol (aHR = 0.12, 95% CI: 0.04–0.32) or testosterone (aHR = 0.36, 95% CI: 0.27–0.48) was significantly associated with lower CVD mortality risk. In females with diabetes, there was a significant association between higher estradiol levels (aHR = 0.22, 95% CI: 0.06–0.83) or T/E ratio (aHR = 0.18, 95% CI: 0.04–0.73) with a reduced all-cause mortality risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identifies some novel associations between estradiol, testosterone, and their ratios with long-term mortality in men and women across different glycemic statuses. These findings suggest a potential protective role of sex hormones in individuals with altered glucose metabolism, with gender difference, warranting further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"481-491"},"PeriodicalIF":3.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A. Mamas, Marat Fudim, Gregg C. Fonarow
Background
The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.
Methods
We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.
Results
From 1999 to 2022, a total of 88,597 T2DM and obesity-related deaths were recorded in the United States. The AAMR consistently increased from 1999 to 2017 (APC: 7.64; 95% CI: 1.91–9.96), followed by a marked rise from 2017 to 2022 (APC: 20.13; 95% CI: 12.88–38.57). The AAMR was approximately 3.58 times higher during the COVID-19 pandemic compared to the period from 1999 to 2019. The AAMR for males was consistently greater than that for females. The highest AAMR was observed in non-Hispanic (NH) Blacks or African Americans, followed by NH White, Hispanic or Latino, and other NH populations. Rural areas (AAMR: 1.86, 95% CI: 1.83–1.89) exhibited a greater AAMR than urban regions 1.26 (95% CI: 1.25–1.27).
Conclusions
Our results indicate a substantial increasing trend of T2D and obesity-related deaths in the United States especially during the COVID-19 pandemic.
{"title":"Rising mortality rates linked to type-2 diabetes and obesity in the United States: An observational analysis from 1999 to 2022","authors":"Mushood Ahmed, Abdullah Nofal, Aimen Shafiq, Hira Javaid, Areeba Ahsan, Zain Ali Nadeem, Raheel Ahmed, Mahboob Alam, Mamas A. Mamas, Marat Fudim, Gregg C. Fonarow","doi":"10.1111/jdi.14386","DOIUrl":"10.1111/jdi.14386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The prevalence of type 2 diabetes (T2D) and obesity are increasing in the United States. However, population-level data for mortality trends due to T2D and obesity are limited. This study aims to assess these death trends among adults in the United States categorized by sex, race, and geographical location.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We queried the CDC-WONDER database for multiple cause of death data of adults aged ≥25 years. The crude mortality rates (CMR), age-adjusted mortality rates (AAMRs), annual percent change (APC), and the average APC (AAPC) along with a 95% confidence interval (CI) were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 1999 to 2022, a total of 88,597 T2DM and obesity-related deaths were recorded in the United States. The AAMR consistently increased from 1999 to 2017 (APC: 7.64; 95% CI: 1.91–9.96), followed by a marked rise from 2017 to 2022 (APC: 20.13; 95% CI: 12.88–38.57). The AAMR was approximately 3.58 times higher during the COVID-19 pandemic compared to the period from 1999 to 2019. The AAMR for males was consistently greater than that for females. The highest AAMR was observed in non-Hispanic (NH) Blacks or African Americans, followed by NH White, Hispanic or Latino, and other NH populations. Rural areas (AAMR: 1.86, 95% CI: 1.83–1.89) exhibited a greater AAMR than urban regions 1.26 (95% CI: 1.25–1.27).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate a substantial increasing trend of T2D and obesity-related deaths in the United States especially during the COVID-19 pandemic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"492-500"},"PeriodicalIF":3.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dai Yamagami, Takahisa Deguchi, Aiko Arimura, Yoshihiko Nishio
Aims/Introduction
We evaluated the 24-h ambulatory blood pressure monitoring data of patients to investigate the relationship between the progression of diabetic polyneuropathy and impaired circadian blood pressure variability.
Materials and Methods
This study included 154 patients with diabetes who were hospitalized for hyperglycemic control. Routine biochemical and hematological tests, ambulatory blood pressure monitoring, screening for diabetic complications, nerve conduction studies, and Holter electrocardiography were carried out on all patients. They were classified according to the Baba classification and the clinical staging for diabetic polyneuropathy, and their ambulatory blood pressure monitoring data were compared.
Results
The patients were classified into stages 0 (n = 64), I (n = 42), II (n = 24), III (n = 11) and IV (n = 13) according to the Baba classification. As the severity of diabetic polyneuropathy progressed, the degree of nocturnal blood pressure reduction decreased and the percentage of patients with riser-type impaired circadian blood pressure variability increased. Similar results were observed in patients classified according to the clinical staging for diabetic polyneuropathy. In the multivariate logistic regression analysis, the severity of diabetic neuropathy and urinary albumin excretion were independently associated with the percentage of patients with riser-type. However, the adjusted odds ratio was the highest for Baba class I and decreased with increasing severity.
Conclusions
Patients with progressive diabetic polyneuropathy and renal impairment often show impaired circadian blood pressure variability. The progression of electrophysiological and clinical neuropathy is associated with riser-type circadian blood pressure variability independent of urinary albumin excretion, insulin therapy, renin–angiotensin–aldosterone system inhibitor medication and body mass index.
{"title":"Relationship between the progression of diabetic polyneuropathy and impaired circadian blood pressure variability","authors":"Dai Yamagami, Takahisa Deguchi, Aiko Arimura, Yoshihiko Nishio","doi":"10.1111/jdi.14282","DOIUrl":"10.1111/jdi.14282","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>We evaluated the 24-h ambulatory blood pressure monitoring data of patients to investigate the relationship between the progression of diabetic polyneuropathy and impaired circadian blood pressure variability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This study included 154 patients with diabetes who were hospitalized for hyperglycemic control. Routine biochemical and hematological tests, ambulatory blood pressure monitoring, screening for diabetic complications, nerve conduction studies, and Holter electrocardiography were carried out on all patients. They were classified according to the Baba classification and the clinical staging for diabetic polyneuropathy, and their ambulatory blood pressure monitoring data were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The patients were classified into stages 0 (<i>n</i> = 64), I (<i>n</i> = 42), II (<i>n</i> = 24), III (<i>n</i> = 11) and IV (<i>n</i> = 13) according to the Baba classification. As the severity of diabetic polyneuropathy progressed, the degree of nocturnal blood pressure reduction decreased and the percentage of patients with riser-type impaired circadian blood pressure variability increased. Similar results were observed in patients classified according to the clinical staging for diabetic polyneuropathy. In the multivariate logistic regression analysis, the severity of diabetic neuropathy and urinary albumin excretion were independently associated with the percentage of patients with riser-type. However, the adjusted odds ratio was the highest for Baba class I and decreased with increasing severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with progressive diabetic polyneuropathy and renal impairment often show impaired circadian blood pressure variability. The progression of electrophysiological and clinical neuropathy is associated with riser-type circadian blood pressure variability independent of urinary albumin excretion, insulin therapy, renin–angiotensin–aldosterone system inhibitor medication and body mass index.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"463-474"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Han Zhang, Hanqing Tang, Yunjuan Gu, Zhuqi Tang, Xiaoqin Zhao, Ranran Zhou, Ping Huang, Rongping Zhang, Xinlei Wang
Aims
To explore the relationships between the delayed monophasic glucose peak during oral glucose tolerance test (OGTT) and early-stage diabetic nephropathy (DN) in patients with type 2 diabetes mellitus(T2DM), and to speculate its potential as a risk factor for early-stage DN.
Materials and Methods
This retrospective observational study included 448 participants, all of whom underwent a 3-h OGTT. Based on peak glucose time, they were categorized into the normal glucose tolerance (NGT) group (n = 76), the early delayed group (n = 98), and the late delayed group (n = 274) for comparison. Furthermore, T2DM patients were subdivided into the non-DN group (n = 293) and the early-stage DN group (n = 79) for comparative analysis.
Results
With the delay in glucose peak time, blood glucose levels increased, insulin secretion function and insulin sensitivity decreased. In logistic regression, ISSI-2 was independently associated with the delay in glucose peak time in patients with T2DM (OR 0.839; 95% CI 0.776–0.907; P < 0.001). Additionally, 2-h plasma glucose, OGIS, and AUCC-peptide0–180 min were independently associated with delayed peak glucose time (all P < 0.001). As glucose peak time was delayed, levels of β2-microglobulin and UACR increased, and the prevalence of early-stage DN also increased (all P < 0.050). The delayed monophasic glucose peak was positively associated with early-stage DN (OR 2.230; 95% CI 1.061–4.687; P = 0.034).
Conclusions
In patients with T2DM, the delayed monophasic glucose peak during OGTT may be an early predictor of early-stage diabetes nephropathy, providing early intervention signals for our clinical work.
{"title":"Association between early-stage diabetic nephropathy and the delayed monophasic glucose peak during oral glucose tolerance test in type 2 diabetes mellitus","authors":"Han Zhang, Hanqing Tang, Yunjuan Gu, Zhuqi Tang, Xiaoqin Zhao, Ranran Zhou, Ping Huang, Rongping Zhang, Xinlei Wang","doi":"10.1111/jdi.14382","DOIUrl":"10.1111/jdi.14382","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the relationships between the delayed monophasic glucose peak during oral glucose tolerance test (OGTT) and early-stage diabetic nephropathy (DN) in patients with type 2 diabetes mellitus(T2DM), and to speculate its potential as a risk factor for early-stage DN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective observational study included 448 participants, all of whom underwent a 3-h OGTT. Based on peak glucose time, they were categorized into the normal glucose tolerance (NGT) group (<i>n</i> = 76), the early delayed group (<i>n</i> = 98), and the late delayed group (<i>n</i> = 274) for comparison. Furthermore, T2DM patients were subdivided into the non-DN group (<i>n</i> = 293) and the early-stage DN group (<i>n</i> = 79) for comparative analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With the delay in glucose peak time, blood glucose levels increased, insulin secretion function and insulin sensitivity decreased. In logistic regression, ISSI-2 was independently associated with the delay in glucose peak time in patients with T2DM (OR 0.839; 95% CI 0.776–0.907; <i>P</i> < 0.001). Additionally, 2-h plasma glucose, OGIS, and AUC<sub>C-peptide0–180 min</sub> were independently associated with delayed peak glucose time (all <i>P</i> < 0.001). As glucose peak time was delayed, levels of β2-microglobulin and UACR increased, and the prevalence of early-stage DN also increased (all <i>P</i> < 0.050). The delayed monophasic glucose peak was positively associated with early-stage DN (OR 2.230; 95% CI 1.061–4.687; <i>P</i> = 0.034).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with T2DM, the delayed monophasic glucose peak during OGTT may be an early predictor of early-stage diabetes nephropathy, providing early intervention signals for our clinical work.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 2","pages":"236-245"},"PeriodicalIF":3.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoting Xi, Xuewei Wang, Jia Ma, Qianbo Chen, Yuxin Zhang, Yaxian Song, Yan Li
Aims/Introduction
Diabetic retinopathy (DR) is a common complication of diabetes that can lead to poor vision and blindness. This study aimed to explore the mechanism of action of miR-130a-3p in DR progression.
Materials and Methods
In this study, we administered a single intraperitoneal injection of 100 mg/kg streptozotocin (STZ) to construct a DR mouse model, and induced a human monocyte cell line (THP-1) to differentiate into M0 macrophages, after which the M0 macrophages were cultured with 30 mM high glucose (HG) as a model of inflammation. The relative gene and protein levels were validated by RT–qPCR and western blotting. Macrophage polarization and retinal damage in the mice were tested using ELISA, MDC staining, immunofluorescence staining, and HE staining.
Results
The results revealed that the expression of miR-130a-3p was low in M1 macrophages, whereas the expression of miR-130a-3p was high in M2 macrophages, and the level of miR-130a-3p was reduced after HG treatment of macrophages. The overexpression of miR-130a-3p attenuated HG- or STZ-induced inflammation, promoted macrophage autophagy, inhibited M1 polarization of macrophages, and attenuated the progression of DR. In addition, YY1 was the downstream target gene of miR-130a-3p, and overexpression of miR-130a-3p inhibited YY1 expression. However, overexpression of YY1 weakened the effect of miR-130a-3p mimic. After further treatment with the PI3K/Akt/mTOR pathway activator 740 Y-P, the effect of YY1 knockdown was weakened, macrophage autophagy was inhibited, and M1 polarization and inflammation were promoted.
Conclusion
miR-130a-3p inhibited the activation of the PI3K/Akt/mTOR pathway by downregulating YY1 expression, thus facilitating macrophage autophagy, inhibiting M1 polarization and the inflammatory response of macrophages, and finally attenuating the progression of DR. The results of this study provide theoretical support for the use of miR-130a-3p as a new target for the treatment of DR.
{"title":"miR-130a-3p enhances autophagy through the YY1/PI3K/AKT/mTOR signaling pathway to regulate macrophage polarization and alleviate diabetic retinopathy","authors":"Xiaoting Xi, Xuewei Wang, Jia Ma, Qianbo Chen, Yuxin Zhang, Yaxian Song, Yan Li","doi":"10.1111/jdi.14381","DOIUrl":"10.1111/jdi.14381","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Diabetic retinopathy (DR) is a common complication of diabetes that can lead to poor vision and blindness. This study aimed to explore the mechanism of action of miR-130a-3p in DR progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this study, we administered a single intraperitoneal injection of 100 mg/kg streptozotocin (STZ) to construct a DR mouse model, and induced a human monocyte cell line (THP-1) to differentiate into M0 macrophages, after which the M0 macrophages were cultured with 30 mM high glucose (HG) as a model of inflammation. The relative gene and protein levels were validated by RT–qPCR and western blotting. Macrophage polarization and retinal damage in the mice were tested using ELISA, MDC staining, immunofluorescence staining, and HE staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results revealed that the expression of miR-130a-3p was low in M1 macrophages, whereas the expression of miR-130a-3p was high in M2 macrophages, and the level of miR-130a-3p was reduced after HG treatment of macrophages. The overexpression of miR-130a-3p attenuated HG- or STZ-induced inflammation, promoted macrophage autophagy, inhibited M1 polarization of macrophages, and attenuated the progression of DR. In addition, YY1 was the downstream target gene of miR-130a-3p, and overexpression of miR-130a-3p inhibited YY1 expression. However, overexpression of YY1 weakened the effect of miR-130a-3p mimic. After further treatment with the PI3K/Akt/mTOR pathway activator 740 Y-P, the effect of YY1 knockdown was weakened, macrophage autophagy was inhibited, and M1 polarization and inflammation were promoted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>miR-130a-3p inhibited the activation of the PI3K/Akt/mTOR pathway by downregulating YY1 expression, thus facilitating macrophage autophagy, inhibiting M1 polarization and the inflammatory response of macrophages, and finally attenuating the progression of DR. The results of this study provide theoretical support for the use of miR-130a-3p as a new target for the treatment of DR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"392-404"},"PeriodicalIF":3.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Insulin icodec is a basal insulin designed for once-weekly administration. This study assessed the pharmacological properties of icodec in Japanese individuals with type 1 diabetes (T1D).
Materials and Methods
In a randomized, open-label, crossover study, 24 Japanese individuals with T1D (20–64 years; glycated hemoglobin ≤9.0%) received once-weekly icodec for 8 weeks and once-daily insulin glargine U100 for 14 days at individual constant equimolar doses per week together with bolus insulin aspart. Individual doses were determined during run-in with glargine U100 titrated to prebreakfast self-measured plasma glucose (SMPG) of 4.4–7.2 mmol/L. Blood samples for icodec pharmacokinetics were taken from the first icodec dose until 35 days after last dose. The steady-state glucose-lowering effect was measured in glucose clamps (target 6.7 mmol/L) during 24–48 h and 150–168 h after last icodec dose and 0–24 h after last glargine U100 dose. One-week glucose-lowering effect of icodec was simulated using a pharmacokinetic/pharmacodynamic model. Hypoglycemia was identified from SMPG during the treatment periods.
Results
Icodec pharmacokinetic steady state was achieved on average after 2–3 weeks of treatment. Model-derived daily glucose-lowering effect during the weekly dosing interval averaged 14.6%, 18.0%, 16.6%, 14.9%, 13.3%, 11.9%, and 10.7%, respectively. Rates of level 2 hypoglycemia (PG <3.0 mmol/L) were 37.3 vs 30.6 episodes per patient-year of exposure for icodec vs glargine U100.
Discussion
Icodec pharmacological properties in Japanese individuals with T1D in this study support the potential of icodec to provide basal insulin coverage with once-weekly dosing in Japanese individuals with diabetes.
{"title":"Pharmacological characteristics of once-weekly insulin icodec in Japanese individuals with type 1 diabetes","authors":"Takashi Eto, Miwa Haranaka, Niels Rode Kristensen, Andrea Navarria, Tomoyuki Nishida, Rasmus Ribel-Madsen, Stinne Byrholdt Søgaard, Inge Birk Halberg","doi":"10.1111/jdi.14384","DOIUrl":"10.1111/jdi.14384","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Insulin icodec is a basal insulin designed for once-weekly administration. This study assessed the pharmacological properties of icodec in Japanese individuals with type 1 diabetes (T1D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In a randomized, open-label, crossover study, 24 Japanese individuals with T1D (20–64 years; glycated hemoglobin ≤9.0%) received once-weekly icodec for 8 weeks and once-daily insulin glargine U100 for 14 days at individual constant equimolar doses per week together with bolus insulin aspart. Individual doses were determined during run-in with glargine U100 titrated to prebreakfast self-measured plasma glucose (SMPG) of 4.4–7.2 mmol/L. Blood samples for icodec pharmacokinetics were taken from the first icodec dose until 35 days after last dose. The steady-state glucose-lowering effect was measured in glucose clamps (target 6.7 mmol/L) during 24–48 h and 150–168 h after last icodec dose and 0–24 h after last glargine U100 dose. One-week glucose-lowering effect of icodec was simulated using a pharmacokinetic/pharmacodynamic model. Hypoglycemia was identified from SMPG during the treatment periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Icodec pharmacokinetic steady state was achieved on average after 2–3 weeks of treatment. Model-derived daily glucose-lowering effect during the weekly dosing interval averaged 14.6%, 18.0%, 16.6%, 14.9%, 13.3%, 11.9%, and 10.7%, respectively. Rates of level 2 hypoglycemia (PG <3.0 mmol/L) were 37.3 vs 30.6 episodes per patient-year of exposure for icodec vs glargine U100.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Icodec pharmacological properties in Japanese individuals with T1D in this study support the potential of icodec to provide basal insulin coverage with once-weekly dosing in Japanese individuals with diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"434-441"},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We briefly summarizes the mechanism of GLP-1RA therapy in HO both in rodents and in humans. We also summarized the clinical trials and case reports of GLP-1RA therapy in HO, especially the more and more often used semaglutide. We are hoping the therapy of GLP-1RA in HO will arouse more attention from clinicians in the future.
{"title":"Glucagon-like pepetide-1 receptor agonist suggests novel therapeutic options for hypothalamic obesity","authors":"Wanlu Ma, Bo Zhang, Xiaoping Chen","doi":"10.1111/jdi.14372","DOIUrl":"10.1111/jdi.14372","url":null,"abstract":"<p>We briefly summarizes the mechanism of GLP-1RA therapy in HO both in rodents and in humans. We also summarized the clinical trials and case reports of GLP-1RA therapy in HO, especially the more and more often used semaglutide. We are hoping the therapy of GLP-1RA in HO will arouse more attention from clinicians in the future.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 3","pages":"357-359"},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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