Adam Russell-Hallinan, Narainrit Karuna, Frank Lezoualc'h, Giuseppe Matullo, Hana Baker, Monique Bernard, Yvan Devaux, Lina Badimon, Gemma Vilahur, Jennifer Rieusset, Geneviève A. Derumeaux, Chris J. Watson
An increasing number of individuals are at high risk of type 2 diabetes (T2DM) and its cardiovascular (CV) complications, which challenges healthcare systems with an increased risk of developing CV diseases. Patients with T2DM exhibit a unique cardiac phenotype termed diabetic cardiomyopathy (DCM). DCM usually involves complex and multifactorial pathogenic drivers, including myocardial inflammation, fibrosis, hypertrophy, and early diastolic dysfunction, which potentially evolve into systolic dysfunction and heart failure. There is a lack of effective treatments for DCM on the basis of the complexity of the disease per se and poor understanding of the mechanisms behind disease development and progression. Despite the considerable research attention on the onset of DCM development and progression, understanding of the full spectrum of pathogenic mechanisms has not yet been fully deciphered. Epigenetic alterations, including DNA methylation, histone modifications, bromodomain extra-terminal (BET)-containing reader proteins, and RNA-based mechanisms (e.g., miRs, lncRNAs, circRNA), are significantly associated with the initiation and evolution of DCM, particularly in the early stage. In this review, we provide insights into the evidence of epigenetic alterations related to DCM development and progression characteristics. Furthermore, the uniqueness of epigenetic changes in DCM in specific cell types within diabetic hearts is discussed. We also review epigenetic cooperation in the context of DCM development and epigenetic biomarkers related to DCM progression. With recent advancements in technology, epitranscriptomics-related to DCM has been uniquely discussed. Finally, this review may provide new avenues for potential implications for future research and the discovery of novel treatment targets for preventing the onset and progression of DCM.
{"title":"Established and Emerging Roles of Epigenetic Regulation in Diabetic Cardiomyopathy","authors":"Adam Russell-Hallinan, Narainrit Karuna, Frank Lezoualc'h, Giuseppe Matullo, Hana Baker, Monique Bernard, Yvan Devaux, Lina Badimon, Gemma Vilahur, Jennifer Rieusset, Geneviève A. Derumeaux, Chris J. Watson","doi":"10.1002/dmrr.70081","DOIUrl":"https://doi.org/10.1002/dmrr.70081","url":null,"abstract":"<p>An increasing number of individuals are at high risk of type 2 diabetes (T2DM) and its cardiovascular (CV) complications, which challenges healthcare systems with an increased risk of developing CV diseases. Patients with T2DM exhibit a unique cardiac phenotype termed diabetic cardiomyopathy (DCM). DCM usually involves complex and multifactorial pathogenic drivers, including myocardial inflammation, fibrosis, hypertrophy, and early diastolic dysfunction, which potentially evolve into systolic dysfunction and heart failure. There is a lack of effective treatments for DCM on the basis of the complexity of the disease per se and poor understanding of the mechanisms behind disease development and progression. Despite the considerable research attention on the onset of DCM development and progression, understanding of the full spectrum of pathogenic mechanisms has not yet been fully deciphered. Epigenetic alterations, including DNA methylation, histone modifications, bromodomain extra-terminal (BET)-containing reader proteins, and RNA-based mechanisms (e.g., miRs, lncRNAs, circRNA), are significantly associated with the initiation and evolution of DCM, particularly in the early stage. In this review, we provide insights into the evidence of epigenetic alterations related to DCM development and progression characteristics. Furthermore, the uniqueness of epigenetic changes in DCM in specific cell types within diabetic hearts is discussed. We also review epigenetic cooperation in the context of DCM development and epigenetic biomarkers related to DCM progression. With recent advancements in technology, epitranscriptomics-related to DCM has been uniquely discussed. Finally, this review may provide new avenues for potential implications for future research and the discovery of novel treatment targets for preventing the onset and progression of DCM.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869164","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}
The restricted availability of cadaveric isolated human donor islets sharply limits progress in clinical trials of islet cell transplantation. Furthermore, the host's general pharmacologic immunosuppression is invariably needed to grant survival and function of the human islet grafts. The former mandates validation of new sources of insulin producing cells. The latter requires new strategies to circumvent use of general immunosuppressive agents. A possible solution to these problems could consist using of human stem cells, whose availability is indefinite, that are suitable for both, differentiation into endocrine cell phenotypes, and genetic manipulations to alter immunogenicity. Pluripotent human stem cells, either embryonic (ESCs), derived from the blastocyst, or those originating from adult somatic cells, artificially induced to pluripotency (iPSCs), or finally, multipotent human adult mesenchymal stem cells (MSCs) may be considered. MSCs are more difficult to trans-differentiate into Beta-like cells, but they hold powerful immunoregulatory properties, and do not pose ethical problems. Both ESCs and iPSCs show pro's and con's, in terms of ethical acceptance (ESCs), and technical feasibility (iPSCs), with the pending immune problems, that might be attenuated by gene editing manoeuvres to render the cells ‘immune evasive’. Early pilot clinical trials with either ESCs or iPSCs in immunosuppressed T1D patients showed that hyperglycemia can be reversed, although challenges remain.
{"title":"Developing Stem Cell Therapy for Type 1 Diabetes Mellitus","authors":"Riccardo Calafiore","doi":"10.1002/dmrr.70079","DOIUrl":"https://doi.org/10.1002/dmrr.70079","url":null,"abstract":"<p>The restricted availability of cadaveric isolated human donor islets sharply limits progress in clinical trials of islet cell transplantation. Furthermore, the host's general pharmacologic immunosuppression is invariably needed to grant survival and function of the human islet grafts. The former mandates validation of new sources of insulin producing cells. The latter requires new strategies to circumvent use of general immunosuppressive agents. A possible solution to these problems could consist using of human stem cells, whose availability is indefinite, that are suitable for both, differentiation into endocrine cell phenotypes, and genetic manipulations to alter immunogenicity. Pluripotent human stem cells, either embryonic (ESCs), derived from the blastocyst, or those originating from adult somatic cells, artificially induced to pluripotency (iPSCs), or finally, multipotent human adult mesenchymal stem cells (MSCs) may be considered. MSCs are more difficult to trans-differentiate into Beta-like cells, but they hold powerful immunoregulatory properties, and do not pose ethical problems. Both ESCs and iPSCs show pro's and con's, in terms of ethical acceptance (ESCs), and technical feasibility (iPSCs), with the pending immune problems, that might be attenuated by gene editing manoeuvres to render the cells ‘immune evasive’. Early pilot clinical trials with either ESCs or iPSCs in immunosuppressed T1D patients showed that hyperglycemia can be reversed, although challenges remain.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853812","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}
People with type 1 diabetes are at risk of complications, including impaired bone health. Hyperglycaemia and accumulation of advanced glycation end products (AGEs) are involved in the development of those. Bone measurements such as trabecular bone score (TBS), high-resolution periphery quantitative computed tomography (HR-pQCT), and impact microindentation may detect impaired bone health better than bone mineral density (BMD). Clinical measures reflecting risk factors such as AGE accumulation or prevalence of cardiovascular autonomic neuropathy may also predict low bone quality.
Methods
This cross-sectional study included 111 adults with type 1 diabetes and 37 healthy sex- and age-matched. Bone health was assessed through DXA with TBS, HR-pQCT and impact microindentation. Accumulation of AGEs was evaluated by skin autofluorescence, and screening for cardiovascular autonomic neuropathy was performed.
Results
The mean (SD) age of the participants was 42.3 (13.8) years and the median (IQR) BMI was 26.9 [24.5; 30.1] kg/m2. Median SkinAGE value was higher in the type 1 diabetes group (2.1 [1.9; 2.7]) than in the control group (1.8 [1.6; 2.3]), p = 0.004. In the diabetes group, SkinAGE correlated with femoral neck, total hip BMD, and TBS. SkinAGE showed predictive value for low TBS upon adjustment for age, sex, and BMI.
Conclusion
In persons with type 1 diabetes, higher levels of AGE accumulation measured by skin autofluorescence are related to a lower BMD as well as a lower TBS. Along with consideration of age, sex, BMI and other risk factors of osteoporosis, a high skin autofluorescence should increase the suspicion of impaired bone health.
1型糖尿病患者有并发症的风险，包括骨骼健康受损。高血糖和晚期糖基化终产物（AGEs）的积累参与了这些疾病的发展。骨测量，如骨小梁评分（TBS）、高分辨率外围定量计算机断层扫描（HR-pQCT）和撞击微压痕，可能比骨矿物质密度（BMD）更好地检测骨骼健康受损。反映诸如AGE积累或心血管自主神经病变患病率等危险因素的临床指标也可以预测低骨质量。方法本横断面研究纳入111例成人1型糖尿病患者和37例性别和年龄相匹配的健康人群。通过DXA、TBS、HR-pQCT和冲击微压痕评估骨健康状况。通过皮肤自身荧光评估AGEs的积累，并进行心血管自主神经病变筛查。结果参与者的平均（SD）年龄为42.3岁（13.8岁），中位（IQR） BMI为26.9 [24.5；30.1 kg / m2。1型糖尿病组中位SkinAGE值较高(2.1 [1.9；2.7])高于对照组(1.8 [1.6；2.3]), p = 0.004。在糖尿病组中，SkinAGE与股骨颈、全髋关节骨密度和TBS相关。在调整年龄、性别和BMI后，SkinAGE显示出低TBS的预测价值。结论在1型糖尿病患者中，皮肤自身荧光测定的较高水平的AGE积累与较低的BMD和较低的TBS有关。考虑到年龄、性别、BMI等骨质疏松的危险因素，高皮肤自身荧光应该增加对骨骼健康受损的怀疑。
{"title":"Skin Autofluorescence May Contribute to Prediction of Low Bone Quality in Type 1 Diabetes—A Clinical Cross-Sectional Study","authors":"Inge Agnete Gerlach Brandt, Peter Vestergaard, Morten Frost, Claus Bogh Juhl, Torben Harsløf","doi":"10.1002/dmrr.70080","DOIUrl":"https://doi.org/10.1002/dmrr.70080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>People with type 1 diabetes are at risk of complications, including impaired bone health. Hyperglycaemia and accumulation of advanced glycation end products (AGEs) are involved in the development of those. Bone measurements such as trabecular bone score (TBS), high-resolution periphery quantitative computed tomography (HR-pQCT), and impact microindentation may detect impaired bone health better than bone mineral density (BMD). Clinical measures reflecting risk factors such as AGE accumulation or prevalence of cardiovascular autonomic neuropathy may also predict low bone quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study included 111 adults with type 1 diabetes and 37 healthy sex- and age-matched. Bone health was assessed through DXA with TBS, HR-pQCT and impact microindentation. Accumulation of AGEs was evaluated by skin autofluorescence, and screening for cardiovascular autonomic neuropathy was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean (SD) age of the participants was 42.3 (13.8) years and the median (IQR) BMI was 26.9 [24.5; 30.1] kg/m<sup>2</sup>. Median SkinAGE value was higher in the type 1 diabetes group (2.1 [1.9; 2.7]) than in the control group (1.8 [1.6; 2.3]), <i>p</i> = 0.004. In the diabetes group, SkinAGE correlated with femoral neck, total hip BMD, and TBS. SkinAGE showed predictive value for low TBS upon adjustment for age, sex, and BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In persons with type 1 diabetes, higher levels of AGE accumulation measured by skin autofluorescence are related to a lower BMD as well as a lower TBS. Along with consideration of age, sex, BMI and other risk factors of osteoporosis, a high skin autofluorescence should increase the suspicion of impaired bone health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144853805","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}
Samuel T. Jerram, Jennie H. M. Yang, Evangelia Williams, Clara Domingo-Vila, Yuk-Fun Liu, Mark Peakman, R. David Leslie, Timothy Tree
Abatacept is a CTLA4-Ig fusion protein that blocks CD80/CD86-dependent T-cell co-stimulation. When administered, Abatacept limits, to a variable degree, loss of stimulated C-peptide secretion in patients with newly-diagnosed type 1 diabetes (T1D), while reducing both circulating memory CD4+ T-cells and T follicular helper (Tfh) cells; however, its precise mechanism of action is not known. To investigate this effect, we studied 12 patients, using multi-parameter flow cytometry, who each self-administered Abatacept in subcutaneous formulation for 6 months within 100 days of diagnosis. Abatacept treatment impacted the CD4+ T cell memory compartment, inducing a reduction in T-effector cells across both conventional (Tconv) and regulatory (Treg) sub-populations. A reduction in activated Tfh cells (CXCR5+PD1+ICOS+), previously described with intravenous therapy, was replicated and extended. An integrated baseline immunological phenotype predicted Abatacept-induced preservation of C-peptide.
{"title":"Subcutaneous Abatacept in New Onset Type 1 Diabetes: Clinical and Immunological Effects","authors":"Samuel T. Jerram, Jennie H. M. Yang, Evangelia Williams, Clara Domingo-Vila, Yuk-Fun Liu, Mark Peakman, R. David Leslie, Timothy Tree","doi":"10.1002/dmrr.70074","DOIUrl":"https://doi.org/10.1002/dmrr.70074","url":null,"abstract":"<p>Abatacept is a CTLA4-Ig fusion protein that blocks CD80/CD86-dependent T-cell co-stimulation. When administered, Abatacept limits, to a variable degree, loss of stimulated C-peptide secretion in patients with newly-diagnosed type 1 diabetes (T1D), while reducing both circulating memory CD4<sup>+</sup> T-cells and T follicular helper (Tfh) cells; however, its precise mechanism of action is not known. To investigate this effect, we studied 12 patients, using multi-parameter flow cytometry, who each self-administered Abatacept in subcutaneous formulation for 6 months within 100 days of diagnosis. Abatacept treatment impacted the CD4<sup>+</sup> T cell memory compartment, inducing a reduction in T-effector cells across both conventional (Tconv) and regulatory (Treg) sub-populations. A reduction in activated Tfh cells (CXCR5<sup>+</sup>PD1<sup>+</sup>ICOS<sup>+</sup>), previously described with intravenous therapy, was replicated and extended. An integrated baseline immunological phenotype predicted Abatacept-induced preservation of C-peptide.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814962","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}
The role of high fasting plasma glucose (HFPG) in ischaemic stroke (IS) has become increasingly prominent. Our study aimed to assess the global and regional distribution of the burden of IS attributable to HFPG (IS-HFPG) and to predict the disease burden of IS-HFPG to 2041.
Methods
This study extracted the data on the burden of IS-HFPG, including the number and age-standardized rate of deaths and disability-adjusted life years (DALYs) from the Global Burden of Disease Study (GBD) 2021. Joinpoint analysis was used to assess trends in IS-HFPG burden between 1990 and 2021. Further analyses were stratified by region, sex, and age groups.
Results
In 2021, the number of deaths and DALYs related to IS-HFPG reached 0.65 million and 12.37 million, respectively. From 1990 to 2021, the global age-standardized mortality rate (ASMR) and DALY (ASDR) for IS-HFPG declined, with an Average Annual Percentage Change (AAPC) of −0.96 (95% CI: −1.06, −0.86) and −0.72 (95% CI: −0.81, −0.62), respectively. Regionally, the ASMR and ASDR were highest in High-middle SDI and lowest in High SDI. ASMR were higher for males than for females, with rates of 9.43 per 100,000 (95% UI: 7.31, 11.75) and 7.07 per 100,000 (95% UI: 5.35, 8.96), respectively. Age-stratified analysis indicates that the elderly population, particularly those over 70 years old, bears the heaviest burden.
Conclusions
Our research indicates that the global ASMR and ASDR attributable to IS-HFPG has a declining trend. However, developing regions confront a burden of mortality and disability associated with IS-HFPG. Notably, male and the elderly are the primary demographics affected by IS-HFPG. Our study underscores the necessity for regions to formulate targeted prevention and treatment strategies that address the specific needs of diverse populations, particularly in low- and middle-income countries.
{"title":"Global, Regional, and National Burden of Ischaemic Stroke Attributed to High Fasting Plasma Glucose: An Analysis of Data From 1990 to 2021","authors":"Hua Xue, Yuqi Zeng, Xinyang Zou, Yongkun Li","doi":"10.1002/dmrr.70071","DOIUrl":"https://doi.org/10.1002/dmrr.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The role of high fasting plasma glucose (HFPG) in ischaemic stroke (IS) has become increasingly prominent. Our study aimed to assess the global and regional distribution of the burden of IS attributable to HFPG (IS-HFPG) and to predict the disease burden of IS-HFPG to 2041.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study extracted the data on the burden of IS-HFPG, including the number and age-standardized rate of deaths and disability-adjusted life years (DALYs) from the Global Burden of Disease Study (GBD) 2021. Joinpoint analysis was used to assess trends in IS-HFPG burden between 1990 and 2021. Further analyses were stratified by region, sex, and age groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2021, the number of deaths and DALYs related to IS-HFPG reached 0.65 million and 12.37 million, respectively. From 1990 to 2021, the global age-standardized mortality rate (ASMR) and DALY (ASDR) for IS-HFPG declined, with an Average Annual Percentage Change (AAPC) of −0.96 (95% CI: −1.06, −0.86) and −0.72 (95% CI: −0.81, −0.62), respectively. Regionally, the ASMR and ASDR were highest in High-middle SDI and lowest in High SDI. ASMR were higher for males than for females, with rates of 9.43 per 100,000 (95% UI: 7.31, 11.75) and 7.07 per 100,000 (95% UI: 5.35, 8.96), respectively. Age-stratified analysis indicates that the elderly population, particularly those over 70 years old, bears the heaviest burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our research indicates that the global ASMR and ASDR attributable to IS-HFPG has a declining trend. However, developing regions confront a burden of mortality and disability associated with IS-HFPG. Notably, male and the elderly are the primary demographics affected by IS-HFPG. Our study underscores the necessity for regions to formulate targeted prevention and treatment strategies that address the specific needs of diverse populations, particularly in low- and middle-income countries.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 6","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758562","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}
Kajal Panchal, Claire Lawson, Sharmin Shabnam, Kamlesh Khunti, Francesco Zaccardi
Aims/Hypothesis
Recent evidence shows decreasing trends for ischaemic heart disease over time in the general population as well as in those with type 2 diabetes. As type 2 diabetes has been associated with an increased risk of both ischaemic and non-ischaemic heart failure, a greater proportion of people with type 2 diabetes could now be presenting with non-ischaemic heart failure phenotypes. We aimed to investigate the risk of incident ischaemic and non-ischaemic heart failure in people with type 2 diabetes.
Methods
We used the Clinical Practice Research Datalink primary care data, linked to hospital and mortality records, to identify newly diagnosed adults with type 2 diabetes between 2000 and 2021, who were matched to up to four people without diabetes by sex, year of birth, and general practice. Ischaemic heart failure was defined as incident heart failure at or following an ischaemic heart disease event; non-ischaemic HF was defined as incident heart failure in the absence of prevalent ischaemic heart disease. We used Poisson and Royston-Parmar models to estimate, respectively, the incidence rates and the hazard ratios (adjusted for sociodemographic and clinical confounders) for ischaemic and non-ischaemic heart failure, comparing people with type 2 diabetes to those without diabetes.
Results
In a cohort of 1,621,090 people (mean age, 60.1 years; 52.8% women; 532,185 with type 2 diabetes), during a median follow-up of 5.8 (interquartile range: 2.6–10.3) years, a heart failure event occurred in 20,016 (3.8%) people with type 2 diabetes (ischaemic: 5046; non-ischaemic: 14,970) and in 29,835 (2.7%) without diabetes (7001 and 22,834, respectively). Age-standardised rates were higher for non-ischaemic (3.18 [95% CI: 3.09–3.27] vs. 2.08 [2.03–2.12] per 1000 person-years in men with type 2 diabetes vs. without diabetes; and 2.47 [2.39–2.54] vs. 1.57 [1.53–1.61], respectively, in women) than ischaemic (corresponding estimates: 1.57 [1.51–1.63] vs. 0.95 [0.92–0.98] and 0.80 [0.76–0.84] vs. 0.46 [0.44–0.48]) heart failure. Comparing people with type 2 diabetes versus those without diabetes, the hazard ratios were larger for ischaemic (adjusted hazard ratio: 1.36 [1.28–1.45] and 1.30 [1.20–1.42] in men and women, respectively) than non-ischaemic (1.12 [1.07–1.16] and 1.10 [1.06–1.14], respectively) heart failure.
Conclusions/Interpretations
The higher rates of non-ischaemic heart failure highlight the need for ear
目的/假设最近的证据表明，随着时间的推移，普通人群以及2型糖尿病患者缺血性心脏病的发病率呈下降趋势。由于2型糖尿病与缺血性和非缺血性心力衰竭的风险增加有关，现在更大比例的2型糖尿病患者可能表现为非缺血性心力衰竭表型。我们的目的是调查2型糖尿病患者发生缺血性和非缺血性心力衰竭的风险。方法：我们使用临床实践研究数据链的初级保健数据，与医院和死亡率记录相关联，以确定2000年至2021年间新诊断的2型糖尿病成年人，这些人按性别、出生年份和一般实践与多达4名无糖尿病患者相匹配。缺血性心力衰竭被定义为在缺血性心脏病事件发生时或之后的偶发性心力衰竭；非缺血性心力衰竭定义为在没有普遍的缺血性心脏病的情况下发生的心力衰竭。我们分别使用泊松模型和罗伊斯顿-帕玛模型来估计缺血性和非缺血性心力衰竭的发病率和风险比（根据社会人口统计学和临床混杂因素进行调整），并将2型糖尿病患者与非糖尿病患者进行比较。结果在1,621,090人的队列中(平均年龄60.1岁；52.8%的女性;532,185例2型糖尿病患者)，在中位随访5.8年（四分位数范围：2.6-10.3）期间，20,016例（3.8%）2型糖尿病患者发生心力衰竭事件(缺血性：5046例；非缺血性：14970例)和非糖尿病29835例（2.7%）（分别为7001例和22834例）。非缺血性的年龄标准化率更高（2型糖尿病男性患者每1000人年3.18 [95% CI: 3.09-3.27] vs. 2.08 [2.03-2.12]）；女性分别为2.47[2.39-2.54]和1.57[1.53-1.61])比缺血性心力衰竭（相应的估计值：1.57[1.51-1.63]比0.95[0.92-0.98]和0.80[0.76-0.84]比0.46[0.44-0.48]）。2型糖尿病患者与非糖尿病患者相比，缺血性心力衰竭的风险比（调整后的男性和女性风险比分别为1.36[1.28-1.45]和1.30[1.20-1.42]）大于非缺血性心力衰竭（分别为1.12[1.07-1.16]和1.10[1.06-1.14]）。结论/解释非缺血性心力衰竭的较高发生率强调了在缺血性心脏病发展之前进行早期预防的必要性，无论是否患有2型糖尿病。与此同时，2型糖尿病患者缺血性心力衰竭的风险更高，这表明这组患者的缺血后预防不理想。
{"title":"Risk of Ischaemic and Non-Ischaemic Heart Failure in People With Type 2 Diabetes: Observational Study in 1.6 Million People in England","authors":"Kajal Panchal, Claire Lawson, Sharmin Shabnam, Kamlesh Khunti, Francesco Zaccardi","doi":"10.1002/dmrr.70072","DOIUrl":"https://doi.org/10.1002/dmrr.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Hypothesis</h3>\u0000 \u0000 <p>Recent evidence shows decreasing trends for ischaemic heart disease over time in the general population as well as in those with type 2 diabetes. As type 2 diabetes has been associated with an increased risk of both ischaemic and non-ischaemic heart failure, a greater proportion of people with type 2 diabetes could now be presenting with non-ischaemic heart failure phenotypes. We aimed to investigate the risk of incident ischaemic and non-ischaemic heart failure in people with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used the Clinical Practice Research Datalink primary care data, linked to hospital and mortality records, to identify newly diagnosed adults with type 2 diabetes between 2000 and 2021, who were matched to up to four people without diabetes by sex, year of birth, and general practice. Ischaemic heart failure was defined as incident heart failure at or following an ischaemic heart disease event; non-ischaemic HF was defined as incident heart failure in the absence of prevalent ischaemic heart disease. We used Poisson and Royston-Parmar models to estimate, respectively, the incidence rates and the hazard ratios (adjusted for sociodemographic and clinical confounders) for ischaemic and non-ischaemic heart failure, comparing people with type 2 diabetes to those without diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In a cohort of 1,621,090 people (mean age, 60.1 years; 52.8% women; 532,185 with type 2 diabetes), during a median follow-up of 5.8 (interquartile range: 2.6–10.3) years, a heart failure event occurred in 20,016 (3.8%) people with type 2 diabetes (ischaemic: 5046; non-ischaemic: 14,970) and in 29,835 (2.7%) without diabetes (7001 and 22,834, respectively). Age-standardised rates were higher for non-ischaemic (3.18 [95% CI: 3.09–3.27] vs. 2.08 [2.03–2.12] per 1000 person-years in men with type 2 diabetes vs. without diabetes; and 2.47 [2.39–2.54] vs. 1.57 [1.53–1.61], respectively, in women) than ischaemic (corresponding estimates: 1.57 [1.51–1.63] vs. 0.95 [0.92–0.98] and 0.80 [0.76–0.84] vs. 0.46 [0.44–0.48]) heart failure. Comparing people with type 2 diabetes versus those without diabetes, the hazard ratios were larger for ischaemic (adjusted hazard ratio: 1.36 [1.28–1.45] and 1.30 [1.20–1.42] in men and women, respectively) than non-ischaemic (1.12 [1.07–1.16] and 1.10 [1.06–1.14], respectively) heart failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions/Interpretations</h3>\u0000 \u0000 <p>The higher rates of non-ischaemic heart failure highlight the need for ear","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716909","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}
Alisa Fishkin, Aliza Rozenberg, Meir Schechter, Dvora R. Sehtman-Shachar, Genya Aharon-Hananel, Gil Leibowitz, Ilan Yanuv, Ofri Mosenzon
Aims
Randomized placebo-controlled clinical trials showed that glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce kidney risk in patients with type 2 diabetes (T2D), prominently in those with chronic kidney disease. It is unclear whether these findings may apply to broader populations of patients with T2D treated in real-world settings and compared to active controls. We summarised real-world data of adverse kidney outcomes among patients with T2D initiating GLP-1 RA versus other glucose-lowering agents.
Materials and Methods
We searched PubMed and Embase for observational cohort studies (April 2005–January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, ≥ 40 or ≥ 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models.
Results
Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49–78 years, 5%–64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05–1.20]), kidney-related hospitalizations (1.66 [1.01–2.73]), and ≥ 40% reduction in eGFR (1.40 [1.27–1.53]), without evidence for differences in risks of ≥ 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing ≥ 50% eGFR reduction (0.84 [0.76–0.92]), kidney-related hospitalizations (0.73 [0.65–0.83]), and ESKD (0.70 [0.63–0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80–0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk.
Conclusions
In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i.
{"title":"Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists Versus Other Glucose-Lowering Agents in People With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Data","authors":"Alisa Fishkin, Aliza Rozenberg, Meir Schechter, Dvora R. Sehtman-Shachar, Genya Aharon-Hananel, Gil Leibowitz, Ilan Yanuv, Ofri Mosenzon","doi":"10.1002/dmrr.70066","DOIUrl":"https://doi.org/10.1002/dmrr.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Randomized placebo-controlled clinical trials showed that glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce kidney risk in patients with type 2 diabetes (T2D), prominently in those with chronic kidney disease. It is unclear whether these findings may apply to broader populations of patients with T2D treated in real-world settings and compared to active controls. We summarised real-world data of adverse kidney outcomes among patients with T2D initiating GLP-1 RA versus other glucose-lowering agents.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We searched PubMed and Embase for observational cohort studies (April 2005–January 2025; PROSPERO CRD42023405356). Initiators of GLP-1 RA were compared to sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl-peptidase 4 inhibitors (DPP4i), sulfonylureas, or basal insulin. Outcomes included risks of albuminuria progression, ≥ 40 or ≥ 50% eGFR reduction from baseline, acute kidney injury (AKI), kidney-related hospitalizations, and end-stage kidney disease (ESKD), per data availability. We synthesised the data using inverse variance-weighted averages of logarithmic hazard ratios (HR)s in random-effect models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-one studies were eligible, encompassing 1,601,389 patients (mean age 49–78 years, 5%–64% women), with 21, 6, 5, and 1 of them using SGLT2i, DPP4i, basal insulin, and sulfonylureas as a comparator, respectively. Compared with SGLT2i, GLP-1 RA initiators had higher risks for AKI (HR [95% CI] 1.12 [1.05–1.20]), kidney-related hospitalizations (1.66 [1.01–2.73]), and ≥ 40% reduction in eGFR (1.40 [1.27–1.53]), without evidence for differences in risks of ≥ 50% eGFR reduction or ESKD. Compared to DPP4i, GLP-1 RA initiators had lower risks for experiencing ≥ 50% eGFR reduction (0.84 [0.76–0.92]), kidney-related hospitalizations (0.73 [0.65–0.83]), and ESKD (0.70 [0.63–0.78]). Similar benefits were observed when comparing GLP-1 RA to sulfonylureas. Compared to basal insulin, GLP-1 RA initiation was associated with a lower risk of albuminuria progression (0.89 [0.80–0.99]), with inconsistent data regarding possible benefits in reducing ESKD risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with T2D, initiation of GLP-1 RA in real-world settings may be associated with improved kidney outcomes compared to DPP4i, sulfonylureas, and basal insulin, and worse kidney outcomes compared to SGLT2i.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681253","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}
Cirrhosis and diabetes mellitus can develop and influence each other. We conducted this study to compare the hepatic outcomes of sodium-glucose cotransporter 2 (SGLT2) inhibitor use versus no-use in patients with liver cirrhosis and type 2 diabetes.
Materials and Methods
We identified patients diagnosed with type 2 diabetes and liver cirrhosis from the Taiwan's National Health Insurance Research Database between 1 January 2000 and 31 December 2021. Multivariable-adjusted Cox proportional hazard models were used to compare the risks of decompensated cirrhosis, liver failure, cardiovascular events and mortality between SGLT2 inhibitor users and nonusers.
Results
The mean follow-up period for SGLT2 inhibitor users and nonusers was 2.86 and 2.66 years, respectively. The incidence rates of mortality during follow-up were 29.97 versus 63.18 per 1000 person-years for SGLT2 inhibitor users and nonusers, respectively. The multivariable-adjusted models showed that SGLT2 inhibitor users had lower risks of all-cause mortality (aHR 0.47, 95% CI 0.42–0.52), decompensated cirrhosis (aHR 0.67 95% CI 0.58–0.77), liver failure (aHR 0.58, 95% CI 0.49–0.69), hepatorenal syndrome (aHR 0.54, 95% CI 0.35–0.85) and major adverse cardiovascular events (aHR 0.80, 95% CI 0.52–0.70) than nonusers. A longer cumulative duration of SGLT2 inhibitors had further lower risks of mortality and decompensated cirrhosis.
Conclusions
This nationwide cohort study showed that SGLT2 inhibitor use was associated with a significantly lower risk of mortality, decompensated cirrhosis, liver failure and cardiovascular events in patients with compensated liver cirrhosis and type 2 diabetes. SGLT2 inhibitors may be an option for diabetes management in patients with compensated liver cirrhosis.
目的肝硬化与糖尿病是相互发展、相互影响的。我们进行了这项研究，以比较在肝硬化和2型糖尿病患者中使用钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂与不使用SGLT2抑制剂的肝脏结局。采用多变量校正Cox比例风险模型比较SGLT2抑制剂使用者和非使用者失代偿性肝硬化、肝功能衰竭、心血管事件和死亡率的风险。结果SGLT2抑制剂使用者和非使用者的平均随访时间分别为2.86年和2.66年。在随访期间，SGLT2抑制剂使用者和非使用者的死亡率分别为每1000人年29.97和63.18。多变量调整模型显示，SGLT2抑制剂使用者的全因死亡率（aHR 0.47, 95% CI 0.42-0.52）、失代偿性肝硬化（aHR 0.67, 95% CI 0.58 - 0.77）、肝功能衰竭（aHR 0.58, 95% CI 0.49-0.69）、肝肾综合征（aHR 0.54, 95% CI 0.35-0.85）和主要不良心血管事件（aHR 0.80, 95% CI 0.52-0.70）的风险低于非使用者。SGLT2抑制剂的累积持续时间越长，死亡率和失代偿性肝硬化的风险就越低。结论：这项全国性队列研究显示，在代偿性肝硬化和2型糖尿病患者中，使用SGLT2抑制剂与死亡率、失代偿性肝硬化、肝功能衰竭和心血管事件的风险显著降低相关。SGLT2抑制剂可能是代偿性肝硬化患者糖尿病治疗的一种选择。
{"title":"Sodium-Glucose Cotransporter 2 Inhibitors Use in Patients With Liver Cirrhosis","authors":"Fu-Shun Yen, Ming-Chih Hou, James Cheng-Chung Wei, Yu-Han Huang, Ying-Hsiu Shih, Chun-Wei Pan, Sing-Ting Wang, Chii-Min Hwu, Chih-Cheng Hsu","doi":"10.1002/dmrr.70070","DOIUrl":"https://doi.org/10.1002/dmrr.70070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cirrhosis and diabetes mellitus can develop and influence each other. We conducted this study to compare the hepatic outcomes of sodium-glucose cotransporter 2 (SGLT2) inhibitor use versus no-use in patients with liver cirrhosis and type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We identified patients diagnosed with type 2 diabetes and liver cirrhosis from the Taiwan's National Health Insurance Research Database between 1 January 2000 and 31 December 2021. Multivariable-adjusted Cox proportional hazard models were used to compare the risks of decompensated cirrhosis, liver failure, cardiovascular events and mortality between SGLT2 inhibitor users and nonusers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean follow-up period for SGLT2 inhibitor users and nonusers was 2.86 and 2.66 years, respectively. The incidence rates of mortality during follow-up were 29.97 versus 63.18 per 1000 person-years for SGLT2 inhibitor users and nonusers, respectively. The multivariable-adjusted models showed that SGLT2 inhibitor users had lower risks of all-cause mortality (aHR 0.47, 95% CI 0.42–0.52), decompensated cirrhosis (aHR 0.67 95% CI 0.58–0.77), liver failure (aHR 0.58, 95% CI 0.49–0.69), hepatorenal syndrome (aHR 0.54, 95% CI 0.35–0.85) and major adverse cardiovascular events (aHR 0.80, 95% CI 0.52–0.70) than nonusers. A longer cumulative duration of SGLT2 inhibitors had further lower risks of mortality and decompensated cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This nationwide cohort study showed that SGLT2 inhibitor use was associated with a significantly lower risk of mortality, decompensated cirrhosis, liver failure and cardiovascular events in patients with compensated liver cirrhosis and type 2 diabetes. SGLT2 inhibitors may be an option for diabetes management in patients with compensated liver cirrhosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Touria Ahaouari, Brenda Berendsen, Nicolaas Schaper, Hans Bosma, Marleen van Greevenbroek, Bastiaan de Galan, Miranda T. Schram, Hans Savelberg, Annemarie Koster
Objective
Peripheral neuropathy (PN) is a common complication of type 2 diabetes mellitus (T2DM). In this study, we determined the independent and combined associations of T2DM and PN with device-based measures of physical activity levels and sedentary behaviour.
Materials and Methods
Cross-sectional data from The Maastricht Study were used (N: 6471, age 59.8 ± 8.8). T2DM was determined with an oral glucose tolerance test and PN was, using a neurothesiometer, defined as an impaired vibration perception threshold (iVPT), that is exceeding 25 V in either one or both halluces. Physical activity and sedentary behaviour outcomes were derived through 8 days of activPAL accelerometer measurement, worn 24 h/day. Multiple linear regression analyses were used with adjustment for demographic, lifestyle and health-related indicators.
Results
In the fully adjusted model, the combined presence of T2DM and iVPT presented the lowest step count (−1407 steps/day [95% CI: −1851, −963]), and showed the lowest time in light-intensity (−27.2 min/day [−38.6, −15.8]) and moderate-to-vigorous physical activity (−9.5 min/day [−12.6, −6.5]). Moreover, those with both conditions had the highest sedentary time (+33.3 min/day [21.4, 45.2]) and longest sedentary bout durations (+1.0 min/bout [0.6, 1.4) compared with those without these conditions.
Discussion
T2DM and PN were both independently associated with lower levels of physical activity and higher levels of sedentary time. The combination of T2DM with PN was associated with particularly low levels of physical activity and higher levels of sedentary time, indicating an additive association. Strategies to improve physical activity in these individuals should address both conditions.
{"title":"Combined Associations of Type 2 Diabetes and Peripheral Neuropathy With Device-Measured Physical Activity and Sedentary Behaviour—The Maastricht Study","authors":"Touria Ahaouari, Brenda Berendsen, Nicolaas Schaper, Hans Bosma, Marleen van Greevenbroek, Bastiaan de Galan, Miranda T. Schram, Hans Savelberg, Annemarie Koster","doi":"10.1002/dmrr.70069","DOIUrl":"https://doi.org/10.1002/dmrr.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Peripheral neuropathy (PN) is a common complication of type 2 diabetes mellitus (T2DM). In this study, we determined the independent and combined associations of T2DM and PN with device-based measures of physical activity levels and sedentary behaviour.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Cross-sectional data from The Maastricht Study were used (<i>N</i>: 6471, age 59.8 ± 8.8). T2DM was determined with an oral glucose tolerance test and PN was, using a neurothesiometer, defined as an impaired vibration perception threshold (iVPT), that is exceeding 25 V in either one or both halluces. Physical activity and sedentary behaviour outcomes were derived through 8 days of activPAL accelerometer measurement, worn 24 h/day. Multiple linear regression analyses were used with adjustment for demographic, lifestyle and health-related indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the fully adjusted model, the combined presence of T2DM and iVPT presented the lowest step count (−1407 steps/day [95% CI: −1851, −963]), and showed the lowest time in light-intensity (−27.2 min/day [−38.6, −15.8]) and moderate-to-vigorous physical activity (−9.5 min/day [−12.6, −6.5]). Moreover, those with both conditions had the highest sedentary time (+33.3 min/day [21.4, 45.2]) and longest sedentary bout durations (+1.0 min/bout [0.6, 1.4) compared with those without these conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>T2DM and PN were both independently associated with lower levels of physical activity and higher levels of sedentary time. The combination of T2DM with PN was associated with particularly low levels of physical activity and higher levels of sedentary time, indicating an additive association. Strategies to improve physical activity in these individuals should address both conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680981","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}
Miri Lutski, Mor Saban, Debbie Novick, Amir Tirosh, Itamar Raz, Anat Tsur, Inbar Zucker
Aims
To evaluate GDM screening compliance and prevalence, and the association between gestational glucose intolerance and 5-year postpartum diabetes mellitus (DM).
Materials and Methods
We used population-based data from three Israeli health maintenance organisations (HMOs), covering 75% of all births in 2016. GDM screening followed a two-step approach: a 50-g 1-h oral glucose challenge test (OGCT), followed by a 100-g 3-h oral glucose tolerance test (OGTT) using Carpenter-Coustan criteria. Data included age, socioeconomic status (SES), results of OGCT and OGTT tests, child birth weight, and gestational age. The dataset was linked to the Israeli National Diabetes Registry to identify postpartum DM. Logistic regression models estimated odds ratios (ORs) for GDM and postpartum DM, adjusting for maternal age, SES, ethnicity, and glucose tolerance status.
Results
Among 128,454 women, 10% were unscreened. Of those screened, 23,451 underwent the full OGTT. GDM prevalence was 4.3%. Postpartum DM incidence was 8.6% in women with GDM, 3.1% with unknown GDM status, and 2.1% with impaired glucose tolerance (IGT) (defined as one abnormal value on the OGTT). Compared with normoglycemia, adjusted ORs for the 5-year postpartum DM were 25.48 (95% CI: 21.80–29.79) for GDM, 10.04 (95% CI: 8.59–11.74) for unknown GDM status, 6.48 (95% CI: 5.07–8.28) for IGT, and 2.17 (95% CI: 1.63–2.88) for abnormal OGCT with normal OGTT. Older age, lower SES, and Arab or Bedouin ethnicity were linked to higher GDM and postpartum DM.
Conclusions
Gestational glucose intolerance and screening gaps were strong predictors of postpartum DM. Age, SES, and ethnicity highlight the need for targeted efforts to reduce health disparities.
{"title":"Gestational Diabetes—Screening, Prevalence and Postpartum Diabetes: Population-Based Cohort Study","authors":"Miri Lutski, Mor Saban, Debbie Novick, Amir Tirosh, Itamar Raz, Anat Tsur, Inbar Zucker","doi":"10.1002/dmrr.70068","DOIUrl":"https://doi.org/10.1002/dmrr.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To evaluate GDM screening compliance and prevalence, and the association between gestational glucose intolerance and 5-year postpartum diabetes mellitus (DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We used population-based data from three Israeli health maintenance organisations (HMOs), covering 75% of all births in 2016. GDM screening followed a two-step approach: a 50-g 1-h oral glucose challenge test (OGCT), followed by a 100-g 3-h oral glucose tolerance test (OGTT) using Carpenter-Coustan criteria. Data included age, socioeconomic status (SES), results of OGCT and OGTT tests, child birth weight, and gestational age. The dataset was linked to the Israeli National Diabetes Registry to identify postpartum DM. Logistic regression models estimated odds ratios (ORs) for GDM and postpartum DM, adjusting for maternal age, SES, ethnicity, and glucose tolerance status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 128,454 women, 10% were unscreened. Of those screened, 23,451 underwent the full OGTT. GDM prevalence was 4.3%. Postpartum DM incidence was 8.6% in women with GDM, 3.1% with unknown GDM status, and 2.1% with impaired glucose tolerance (IGT) (defined as one abnormal value on the OGTT). Compared with normoglycemia, adjusted ORs for the 5-year postpartum DM were 25.48 (95% CI: 21.80–29.79) for GDM, 10.04 (95% CI: 8.59–11.74) for unknown GDM status, 6.48 (95% CI: 5.07–8.28) for IGT, and 2.17 (95% CI: 1.63–2.88) for abnormal OGCT with normal OGTT. Older age, lower SES, and Arab or Bedouin ethnicity were linked to higher GDM and postpartum DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Gestational glucose intolerance and screening gaps were strong predictors of postpartum DM. Age, SES, and ethnicity highlight the need for targeted efforts to reduce health disparities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"41 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646821","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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