Hannah G. Gordon, Alexis Shub, Susan P. Walker, Richard J. Hiscock, Jessica Atkinson, Stephen Tong, Roxanne M. Hastie, Anthea C. Lindquist, Natasha L. Pritchard
OBJECTIVE To determine the relationships between diabetes in pregnancy, birth weight, and stillbirth risk, using population-based data. RESEARCH DESIGN AND METHODS All singleton births in Victoria, Australia, between 2009 and 2020 were linked with perinatal and diabetes data. For each diabetes subgroup (type 1, type 2, and gestational diabetes [diet-controlled, insulin-controlled]), we assessed the proportion of infants with a birth weight in <10th or >97th centile, the probability of stillbirth by birth weight centile, and stillbirth rate per 1,000 pregnancies across gestational age. RESULTS Our study cohort of 860,042 included 100,856 pregnancies (11.7%) complicated by diabetes in pregnancy. Compared with no diabetes, women with diabetes in pregnancy gave birth earlier (median gestation 38.7 weeks vs. 39.4) and had more iatrogenic births (65% vs. 44%). Gestational diabetes was associated with a lower overall risk of stillbirth compared with no diabetes (diet-controlled: relative risk [RR] 0.75 [95% CI 0.64–0.89]; insulin-controlled: RR 0.37 [95% CI 0.25–0.50]). Compared with no diabetes, preexisting diabetes was associated with an increased risk of stillbirth (RR 2.68 [95% CI 2.01–3.56]), with this trend persisting across all gestational ages and birth weights. This was particularly observed among infants in the >97th centile (type 1 diabetes: RR 3.96 [95% CI 1.23–12.76]; type 2 diabetes: RR 4.02 [95% CI 1.71–9.47]). CONCLUSIONS In our cohort, gestational diabetes was associated with a lower stillbirth risk compared with no diabetes, which potentially can be explained by increased monitoring and earlier iatrogenic delivery. Preexisting diabetes was associated with a higher overall risk of stillbirth, with macrosomic fetuses in the >97th centile representing a particularly high-risk group requiring close monitoring.
目的利用基于人群的数据，确定妊娠期糖尿病、出生体重和死产风险之间的关系。研究设计和方法澳大利亚维多利亚州2009年至2020年间的所有单胎分娩与围产期和糖尿病数据相关。对于每一个糖尿病亚组（1型、2型和妊娠期糖尿病[饮食控制、胰岛素控制]），我们评估了出生体重低于1 / 3的婴儿比例。第十或&；gt；第97百分位，按出生体重百分位计算的死产概率，以及整个妊娠期每1000例妊娠的死产率。结果：860,042例研究队列包括100,856例妊娠合并糖尿病（11.7%）。与未患糖尿病的妇女相比，妊娠期患有糖尿病的妇女分娩更早（中位妊娠期38.7周对39.4周），医源性分娩更多（65%对44%）。与无糖尿病患者相比，妊娠期糖尿病患者死产的总体风险较低（饮食控制：相对风险[RR] 0.75 [95% CI 0.64-0.89]；胰岛素控制：RR 0.37 [95% CI 0.25-0.50]）。与未患糖尿病的孕妇相比，先前存在的糖尿病与死产风险增加相关（RR 2.68 [95% CI 2.01-3.56]），这种趋势在所有胎龄和出生体重中持续存在。这在婴儿中尤为明显。第97百分位（1型糖尿病：RR 3.96 [95% CI 1.23-12.76]； 2型糖尿病：RR 4.02 [95% CI 1.71-9.47]）。结论：在我们的队列中，与无糖尿病患者相比，妊娠期糖尿病与较低的死产风险相关，这可能是由于监测的增加和早期医源性分娩所致。先前存在的糖尿病与死产的总体风险较高有关，与巨大胎儿有关；第97百分位代表需要密切监测的特别高危人群。
{"title":"Maternal Diabetes, Fetal Growth and Stillbirth Risk: A Population-Wide Retrospective Cohort Study From Victoria, Australia","authors":"Hannah G. Gordon, Alexis Shub, Susan P. Walker, Richard J. Hiscock, Jessica Atkinson, Stephen Tong, Roxanne M. Hastie, Anthea C. Lindquist, Natasha L. Pritchard","doi":"10.2337/dc25-0833","DOIUrl":"https://doi.org/10.2337/dc25-0833","url":null,"abstract":"OBJECTIVE To determine the relationships between diabetes in pregnancy, birth weight, and stillbirth risk, using population-based data. RESEARCH DESIGN AND METHODS All singleton births in Victoria, Australia, between 2009 and 2020 were linked with perinatal and diabetes data. For each diabetes subgroup (type 1, type 2, and gestational diabetes [diet-controlled, insulin-controlled]), we assessed the proportion of infants with a birth weight in &lt;10th or &gt;97th centile, the probability of stillbirth by birth weight centile, and stillbirth rate per 1,000 pregnancies across gestational age. RESULTS Our study cohort of 860,042 included 100,856 pregnancies (11.7%) complicated by diabetes in pregnancy. Compared with no diabetes, women with diabetes in pregnancy gave birth earlier (median gestation 38.7 weeks vs. 39.4) and had more iatrogenic births (65% vs. 44%). Gestational diabetes was associated with a lower overall risk of stillbirth compared with no diabetes (diet-controlled: relative risk [RR] 0.75 [95% CI 0.64–0.89]; insulin-controlled: RR 0.37 [95% CI 0.25–0.50]). Compared with no diabetes, preexisting diabetes was associated with an increased risk of stillbirth (RR 2.68 [95% CI 2.01–3.56]), with this trend persisting across all gestational ages and birth weights. This was particularly observed among infants in the &gt;97th centile (type 1 diabetes: RR 3.96 [95% CI 1.23–12.76]; type 2 diabetes: RR 4.02 [95% CI 1.71–9.47]). CONCLUSIONS In our cohort, gestational diabetes was associated with a lower stillbirth risk compared with no diabetes, which potentially can be explained by increased monitoring and earlier iatrogenic delivery. Preexisting diabetes was associated with a higher overall risk of stillbirth, with macrosomic fetuses in the &gt;97th centile representing a particularly high-risk group requiring close monitoring.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"14 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer R. Snaith, Phoom Narongkiatikhun, Petter Bjornstad, Jerry R. Greenfield, Kalie L. Tommerdahl
In type 1 diabetes, a condition that necessitates lifelong exogenous insulin replacement, there is heavy reliance on technology-assisted insulin delivery and glucose monitoring. Yet, people living with type 1 diabetes still face dysglycemia, weight gain, vascular complications, ketoacidosis and severe hypoglycemia, and psychological distress. Cardiovascular and kidney disease remain the leading causes of morbidity and mortality, yet traditional risk factors (smoking, hypertension, hyperlipidemia, obesity, hyperglycemia) incompletely explain this excess burden. Emerging evidence highlights the role of insulin resistance, inflammation, and endothelial dysfunction exacerbated by current subcutaneous insulin therapies in type 1 diabetes, independent of overweight/obesity status. This has fueled interest in addressing metabolic challenges in type 1 diabetes through novel insulin analogs, adjunctive noninsulin therapies, and integrated technologies. Our review explores the potential synergy between technologies and adjunctive therapeutics to address unique physiologic drivers of metabolic dysfunction in type 1 diabetes. Innovations such as multihormonal systems, dynamic glucose and ketone monitoring, and automated insulin titration hold promise. However, leveraging emerging insights from nutrient-stimulated hormone-based therapies and other drug classes such as insulin-sensitizing agents and sodium–glucose cotransporter 2 inhibitors could pave the way for designing combination type 1 diabetes–specific therapies. Large, placebo-controlled trials are needed to progress the field toward use of combination therapies that reduce metabolic and vascular complications and ease patient burden in type 1 diabetes.
{"title":"Advancing Type 1 Diabetes Management: Integrating Novel Therapies, Technologies, and Adjunctive Approaches","authors":"Jennifer R. Snaith, Phoom Narongkiatikhun, Petter Bjornstad, Jerry R. Greenfield, Kalie L. Tommerdahl","doi":"10.2337/dci25-0015","DOIUrl":"https://doi.org/10.2337/dci25-0015","url":null,"abstract":"In type 1 diabetes, a condition that necessitates lifelong exogenous insulin replacement, there is heavy reliance on technology-assisted insulin delivery and glucose monitoring. Yet, people living with type 1 diabetes still face dysglycemia, weight gain, vascular complications, ketoacidosis and severe hypoglycemia, and psychological distress. Cardiovascular and kidney disease remain the leading causes of morbidity and mortality, yet traditional risk factors (smoking, hypertension, hyperlipidemia, obesity, hyperglycemia) incompletely explain this excess burden. Emerging evidence highlights the role of insulin resistance, inflammation, and endothelial dysfunction exacerbated by current subcutaneous insulin therapies in type 1 diabetes, independent of overweight/obesity status. This has fueled interest in addressing metabolic challenges in type 1 diabetes through novel insulin analogs, adjunctive noninsulin therapies, and integrated technologies. Our review explores the potential synergy between technologies and adjunctive therapeutics to address unique physiologic drivers of metabolic dysfunction in type 1 diabetes. Innovations such as multihormonal systems, dynamic glucose and ketone monitoring, and automated insulin titration hold promise. However, leveraging emerging insights from nutrient-stimulated hormone-based therapies and other drug classes such as insulin-sensitizing agents and sodium–glucose cotransporter 2 inhibitors could pave the way for designing combination type 1 diabetes–specific therapies. Large, placebo-controlled trials are needed to progress the field toward use of combination therapies that reduce metabolic and vascular complications and ease patient burden in type 1 diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"8 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Philip M. Clarke, Xinyang Hua, Ruth L. Coleman, John Chalmers, Mark Woodward, Jennifer B. Green, Darren K. McGuire, Lee-Ling Lim, Amanda I. Adler, Rury R. Holman
OBJECTIVE To examine differences in case-fatality incidence among individuals with type 2 diabetes after major coronary or cerebrovascular events by geographic region and country income level. RESEARCH DESIGN AND METHODS We studied ADVANCE, TECOS, and EXSCEL participants who experienced within-trial major coronary (fatal or nonfatal myocardial infarction or sudden cardiac death) or cerebrovascular (fatal or nonfatal stroke) events. Case fatality was defined as death at the time or within 30 days of an event. We compared geographic regions with the reference category (Western Europe, North America, or Australia and New Zealand) and compared medium- and low-income countries, based on gross national income per capita by the World Bank, with the reference category (high). Unadjusted and adjusted analyses were performed for each trial using logistic regression for individual participant data, and the results were meta-analyzed. Adjustments were made for previous cardiovascular events and risk factors. RESULTS There were 2,574 major coronary and 1,247 cerebrovascular events among the 40,563 study participants. Postcoronary case-fatality adjusted odds ratios (95% CIs), compared with the reference group, were 3.31 (2.32–4.72), 2.78 (2.11–3.66), and 2.84 (1.71–4.73) for Asia, Central and Eastern Europe, and South America and Africa, respectively. The odds ratio for low- and middle-income versus high-income countries was 3.07 (2.41–3.92). Case fatality after a major cerebrovascular event did not differ by geographic region or income group. CONCLUSIONS Postcoronary case fatality was substantially higher in Asia, Central and Eastern Europe, and South America and Africa compared with Western countries and higher in low- and middle-income countries compared with high-income countries.
{"title":"International Variation in Case Fatality After Major Coronary or Cerebrovascular Events in Individuals With Type 2 Diabetes: Evidence From ADVANCE, TECOS, and EXSCEL","authors":"Philip M. Clarke, Xinyang Hua, Ruth L. Coleman, John Chalmers, Mark Woodward, Jennifer B. Green, Darren K. McGuire, Lee-Ling Lim, Amanda I. Adler, Rury R. Holman","doi":"10.2337/dc25-0541","DOIUrl":"https://doi.org/10.2337/dc25-0541","url":null,"abstract":"OBJECTIVE To examine differences in case-fatality incidence among individuals with type 2 diabetes after major coronary or cerebrovascular events by geographic region and country income level. RESEARCH DESIGN AND METHODS We studied ADVANCE, TECOS, and EXSCEL participants who experienced within-trial major coronary (fatal or nonfatal myocardial infarction or sudden cardiac death) or cerebrovascular (fatal or nonfatal stroke) events. Case fatality was defined as death at the time or within 30 days of an event. We compared geographic regions with the reference category (Western Europe, North America, or Australia and New Zealand) and compared medium- and low-income countries, based on gross national income per capita by the World Bank, with the reference category (high). Unadjusted and adjusted analyses were performed for each trial using logistic regression for individual participant data, and the results were meta-analyzed. Adjustments were made for previous cardiovascular events and risk factors. RESULTS There were 2,574 major coronary and 1,247 cerebrovascular events among the 40,563 study participants. Postcoronary case-fatality adjusted odds ratios (95% CIs), compared with the reference group, were 3.31 (2.32–4.72), 2.78 (2.11–3.66), and 2.84 (1.71–4.73) for Asia, Central and Eastern Europe, and South America and Africa, respectively. The odds ratio for low- and middle-income versus high-income countries was 3.07 (2.41–3.92). Case fatality after a major cerebrovascular event did not differ by geographic region or income group. CONCLUSIONS Postcoronary case fatality was substantially higher in Asia, Central and Eastern Europe, and South America and Africa compared with Western countries and higher in low- and middle-income countries compared with high-income countries.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"10 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edyta Schaefer, Janett Barbaresko, Michael Roden, Oliver Kuss, Sabrina Schlesinger
OBJECTIVE To investigate the association between adherence to a plant-based dietary index (PDI), healthy PDI, and unhealthy PDI with all-cause mortality in people with type 2 diabetes and to assess whether associations varied by diabetes subgroups. RESEARCH DESIGN AND METHODS We included 4,829 UK Biobank participants with type 2 diabetes and at least two 24-h dietary recalls. We generated overall, healthy, and unhealthy scores. Multivariable Cox regression estimated hazard ratios (HRs) and 95% CIs for all-cause mortality, comparing the highest tertile (T3) with the lowest T1 of adherence to PDI, a healthy PDI, and an unhealthy PDI. Interactions between PDI adherence and diabetes subgroups (HbA1c, waist circumference, age at diagnosis, diabetes duration) were assessed by two-dimensional B-splines and by including product terms into the model. RESULTS During a mean follow-up of 11.3 years, 679 deaths occurred. Individuals with the highest PDI adherence, compared with those with lowest, were at lower risk of all-cause mortality (T3 vs. T1: HR 0.79 [95% CI 0.63; 0.99]), and a similar direction was observed for those with a healthy PDI (0.82 [0.67; 1.02]) but the 95% CI included the null value. Unhealthy PDI was associated with increased mortality risk (1.24 [1.00; 1.54]). The associations of PDI, healthy PDI, and unhealthy PDI with all-cause mortality risk were more pronounced for those with poorer glycemic control, higher waist circumference, diagnosis earlier in life, and longer diabetes duration. CONCLUSIONS Higher PDI adherence was associated with decreased mortality risk and higher unhealthy PDI adherence with an increased mortality risk. There was an indication for differences in these association depending on diabetes subgroups.
目的研究坚持植物性饮食指数（PDI）、健康PDI和不健康PDI与2型糖尿病患者全因死亡率之间的关系，并评估这种关系是否因糖尿病亚组而异。研究设计和方法我们纳入了4829名英国生物银行参与者，他们患有2型糖尿病，并且至少有两次24小时饮食回顾。我们生成了总体、健康和不健康的分数。多变量Cox回归估计了全因死亡率的风险比（hr）和95% ci，比较了坚持PDI、健康PDI和不健康PDI的最高终点（T3）和最低终点（T1）。PDI依从性与糖尿病亚组（HbA1c、腰围、诊断时年龄、糖尿病持续时间）之间的相互作用通过二维b样条和将产品项纳入模型来评估。结果：在平均11.3年的随访期间，发生679例死亡。与PDI依从性最低的个体相比，PDI依从性最高的个体全因死亡风险较低（T3 vs. T1: HR 0.79 [95% CI 0.63; 0.99]）， PDI健康的个体也有类似的趋势（0.82[0.67;1.02]），但95% CI包括零值。不健康的PDI与死亡风险增加相关（1.24[1.00;1.54]）。PDI、健康PDI和不健康PDI与全因死亡风险的关联在血糖控制较差、腰围较高、生命早期诊断和糖尿病病程较长的患者中更为明显。结论：较高的PDI依从性与死亡风险降低有关，而较高的不健康PDI依从性与死亡风险增加有关。有迹象表明，根据糖尿病亚组，这些关联存在差异。
{"title":"Plant-Based Dietary Patterns Associated With Reduced Risk of All-Cause Mortality in Diabetes Subgroups: A Prospective Cohort Study From the UK Biobank","authors":"Edyta Schaefer, Janett Barbaresko, Michael Roden, Oliver Kuss, Sabrina Schlesinger","doi":"10.2337/dc25-0344","DOIUrl":"https://doi.org/10.2337/dc25-0344","url":null,"abstract":"OBJECTIVE To investigate the association between adherence to a plant-based dietary index (PDI), healthy PDI, and unhealthy PDI with all-cause mortality in people with type 2 diabetes and to assess whether associations varied by diabetes subgroups. RESEARCH DESIGN AND METHODS We included 4,829 UK Biobank participants with type 2 diabetes and at least two 24-h dietary recalls. We generated overall, healthy, and unhealthy scores. Multivariable Cox regression estimated hazard ratios (HRs) and 95% CIs for all-cause mortality, comparing the highest tertile (T3) with the lowest T1 of adherence to PDI, a healthy PDI, and an unhealthy PDI. Interactions between PDI adherence and diabetes subgroups (HbA1c, waist circumference, age at diagnosis, diabetes duration) were assessed by two-dimensional B-splines and by including product terms into the model. RESULTS During a mean follow-up of 11.3 years, 679 deaths occurred. Individuals with the highest PDI adherence, compared with those with lowest, were at lower risk of all-cause mortality (T3 vs. T1: HR 0.79 [95% CI 0.63; 0.99]), and a similar direction was observed for those with a healthy PDI (0.82 [0.67; 1.02]) but the 95% CI included the null value. Unhealthy PDI was associated with increased mortality risk (1.24 [1.00; 1.54]). The associations of PDI, healthy PDI, and unhealthy PDI with all-cause mortality risk were more pronounced for those with poorer glycemic control, higher waist circumference, diagnosis earlier in life, and longer diabetes duration. CONCLUSIONS Higher PDI adherence was associated with decreased mortality risk and higher unhealthy PDI adherence with an increased mortality risk. There was an indication for differences in these association depending on diabetes subgroups.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"11 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janni E. Larsson, Lonny Stokholm, Toke Bek, Nis Andersen, Jens Andresen, Javad Hajari, Steffen Heegaard, Kurt Højlund, Ryo Kawasaki, Sören Möller, Frederik N. Pedersen, Katja C. Schielke, Anne Thykjær Petersen, Jakob Grauslund, Elisabeth R. Mathiesen, Caroline S. Laugesen
OBJECTIVE To evaluate the risk of treatment of sight-threatening diabetic retinopathy (DR) defined as panretinal photocoagulation for proliferative DR or anti–vascular endothelial growth factor injections for diabetic macular edema (DME) during and after pregnancy compared with nonpregnant control participants. RESEARCH DESIGN AND METHODS This was a matched cohort study of women with type 1 diabetes who gave birth in 2013–2022 and who had DR levels recorded in the national Danish Registry of Diabetic Retinopathy during and after pregnancy. Control participants consisted of nonpregnant women with type 1 diabetes, individually matched by baseline DR level. Data were collected from relevant national registers from 36 months before pregnancy until 36 months after. RESULTS We included 1,041 pregnant women and 1,041 matched control participants. At baseline, the median duration (interquartile range [IQR]) of diabetes was 13 (6, 19) and 10 (5, 17) years for cases and control participants. Median baseline HbA1c (IQR) was 57 (50, 67) compared with 64 (55, 79) mmol/mol (7.4% vs. 8%), and DR was present in 42.7% of both groups. During and after pregnancy, treatment of proliferative DR with panretinal photocoagulation occurred to a similar extent in both groups (pregnant women vs. control participants: during treatment: 1.2% vs. 1.1%, respectively, OR 1.18 [95% CI 0.53, 2.66]); and after treatment: 2.7% vs. 2.9%, respectively, OR 0.93 [95% CI 0.55, 1.57]). Treatment of DME was rare in both groups. Progression to proliferative DR was not higher in the pregnant group (adjusted hazard ratio 0.64 [95% CI 0.32, 1.31]). CONCLUSIONS In this nationwide register study of women with type 1 diabetes, pregnant women and retinopathy-matched, nonpregnant control participants had a similar risk of developing sight-threatening DR requiring treatment during and within 36 months after pregnancy.
目的：与未怀孕的对照组相比，评估妊娠期间和妊娠后治疗威胁视力的糖尿病视网膜病变（DR）的风险，DR定义为增殖性DR的全视网膜光凝治疗或抗血管内皮生长因子注射治疗糖尿病黄斑水肿（DME）。研究设计和方法这是一项匹配队列研究，研究对象为2013-2022年分娩的1型糖尿病女性，她们在怀孕期间和怀孕后的糖尿病视网膜病变国家登记处记录了DR水平。对照组由未怀孕的1型糖尿病妇女组成，分别与基线DR水平相匹配。从怀孕前36个月到怀孕后36个月的相关国家登记处收集数据。结果我们纳入了1041名孕妇和1041名匹配的对照受试者。在基线时，糖尿病患者和对照组的中位病程（四分位数范围[IQR]）分别为13年（6,19年）和10年（5,17年）。中位基线HbA1c （IQR）为57 (50,67)mmol/mol, 64 (55,79) mmol/mol(7.4%对8%)，两组均有42.7%的患者出现DR。在怀孕期间和怀孕后，两组用全视网膜光凝治疗增散性DR的发生率相似（孕妇与对照组：治疗期间分别为1.2%对1.1%，OR为1.18 [95% CI 0.53, 2.66]）；治疗后：2.7% vs. 2.9%, OR 0.93 [95% CI 0.55, 1.57])。两组均未见DME治疗。妊娠组向增殖性DR的进展并不高（校正风险比0.64 [95% CI 0.32, 1.31]）。结论：在这项全国范围内登记的1型糖尿病女性、孕妇和视网膜病变匹配的非怀孕对照参与者在怀孕期间和怀孕后36个月内发生视力威胁DR需要治疗的风险相似。
{"title":"Sight-Threatening Diabetic Retinopathy During and After Pregnancy—A Nationwide Matched-Cohort Study","authors":"Janni E. Larsson, Lonny Stokholm, Toke Bek, Nis Andersen, Jens Andresen, Javad Hajari, Steffen Heegaard, Kurt Højlund, Ryo Kawasaki, Sören Möller, Frederik N. Pedersen, Katja C. Schielke, Anne Thykjær Petersen, Jakob Grauslund, Elisabeth R. Mathiesen, Caroline S. Laugesen","doi":"10.2337/dc25-0758","DOIUrl":"https://doi.org/10.2337/dc25-0758","url":null,"abstract":"OBJECTIVE To evaluate the risk of treatment of sight-threatening diabetic retinopathy (DR) defined as panretinal photocoagulation for proliferative DR or anti–vascular endothelial growth factor injections for diabetic macular edema (DME) during and after pregnancy compared with nonpregnant control participants. RESEARCH DESIGN AND METHODS This was a matched cohort study of women with type 1 diabetes who gave birth in 2013–2022 and who had DR levels recorded in the national Danish Registry of Diabetic Retinopathy during and after pregnancy. Control participants consisted of nonpregnant women with type 1 diabetes, individually matched by baseline DR level. Data were collected from relevant national registers from 36 months before pregnancy until 36 months after. RESULTS We included 1,041 pregnant women and 1,041 matched control participants. At baseline, the median duration (interquartile range [IQR]) of diabetes was 13 (6, 19) and 10 (5, 17) years for cases and control participants. Median baseline HbA1c (IQR) was 57 (50, 67) compared with 64 (55, 79) mmol/mol (7.4% vs. 8%), and DR was present in 42.7% of both groups. During and after pregnancy, treatment of proliferative DR with panretinal photocoagulation occurred to a similar extent in both groups (pregnant women vs. control participants: during treatment: 1.2% vs. 1.1%, respectively, OR 1.18 [95% CI 0.53, 2.66]); and after treatment: 2.7% vs. 2.9%, respectively, OR 0.93 [95% CI 0.55, 1.57]). Treatment of DME was rare in both groups. Progression to proliferative DR was not higher in the pregnant group (adjusted hazard ratio 0.64 [95% CI 0.32, 1.31]). CONCLUSIONS In this nationwide register study of women with type 1 diabetes, pregnant women and retinopathy-matched, nonpregnant control participants had a similar risk of developing sight-threatening DR requiring treatment during and within 36 months after pregnancy.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"19 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVE The predictive power of urinary titin for incident sarcopenia was studied in Japanese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Baseline urinary titin levels were measured, and sarcopenia was evaluated annually using the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Kaplan-Meier curves, Cox models, and time-dependent receiver operating characteristic analyses were used to assess incident sarcopenia. RESULTS Among 444 participants (median follow-up, 1,078 days), 41 developed sarcopenia. The high titin tertile was associated with an elevated sarcopenia risk (log-rank P = 0.04). Cox models associated titin with sarcopenia (adjusted hazard ratio per SD 1.37, 95% CI 1.05–1.77, P = 0.019) and low muscle strength. Risk estimates were consistent across subgroups, including those aged ≥70 years, men, individuals with BMI <25 kg/m2, HbA1c ≥7%, and estimated glomerular filtration rate ≥60 mL/min/1.73 m2 (P for interaction > 0.05). CONCLUSIONS Elevated urinary titin levels predict sarcopenia and low muscle strength in individuals with type 2 diabetes, supporting its use as a noninvasive biomarker.
目的研究尿titin对日本2型糖尿病患者肌肉减少症的预测能力。研究设计和方法测量基线尿titin水平，并使用亚洲肌肉减少症工作组（AWGS） 2019标准每年评估肌肉减少症。Kaplan-Meier曲线、Cox模型和随时间变化的受试者工作特征分析用于评估肌肉减少症。结果：在444名参与者中（中位随访1078天），41人发生了肌肉减少症。高titin水平与肌少症风险升高相关（log-rank P = 0.04）。Cox模型将titin与肌肉减少症（校正风险比/ SD 1.37, 95% CI 1.05-1.77, P = 0.019）和低肌力相关。风险估计在亚组中是一致的，包括年龄≥70岁的人、男性、BMI和lt；25 kg/m2, HbA1c≥7%，估计肾小球滤过率≥60 mL/min/1.73 m2（相互作用P < 0.05）。结论尿titin水平升高可预测2型糖尿病患者的肌肉减少症和低肌力，支持其作为无创生物标志物的应用。
{"title":"Prediction of Sarcopenia Onset in Type 2 Diabetes Using Urinary Titin Levels: A Japanese Prospective Cohort Study","authors":"Hayato Tanabe, Yoshinori Takiguchi, Rie Tsutsumi, Kaori Shiroma, Mizusa Hyodo, Yuna Izumi-Mishima, Kazuhiro Nomura, Masafumi Matsuo, Hiroshi Sakaue, Michio Shimabukuro","doi":"10.2337/dc25-1067","DOIUrl":"https://doi.org/10.2337/dc25-1067","url":null,"abstract":"OBJECTIVE The predictive power of urinary titin for incident sarcopenia was studied in Japanese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Baseline urinary titin levels were measured, and sarcopenia was evaluated annually using the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Kaplan-Meier curves, Cox models, and time-dependent receiver operating characteristic analyses were used to assess incident sarcopenia. RESULTS Among 444 participants (median follow-up, 1,078 days), 41 developed sarcopenia. The high titin tertile was associated with an elevated sarcopenia risk (log-rank P = 0.04). Cox models associated titin with sarcopenia (adjusted hazard ratio per SD 1.37, 95% CI 1.05–1.77, P = 0.019) and low muscle strength. Risk estimates were consistent across subgroups, including those aged ≥70 years, men, individuals with BMI &lt;25 kg/m2, HbA1c ≥7%, and estimated glomerular filtration rate ≥60 mL/min/1.73 m2 (P for interaction &gt; 0.05). CONCLUSIONS Elevated urinary titin levels predict sarcopenia and low muscle strength in individuals with type 2 diabetes, supporting its use as a noninvasive biomarker.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"12 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sissel Banner Lundemose, Ajenthen Gayathri Ranjan, Ole Nørgaard, Tommi Suvitaival, Kirsten Nørgaard
OBJECTIVE People with type 1 diabetes (T1D) struggle to manage exercise because of hypoglycemia risk. RESEARCH DESIGN AND METHODS This systematic review and meta-analysis evaluated low-dose glucagon's efficacy for preventing and treating exercise-induced hypoglycemia in T1D. Medline, Embase, and Cochrane CENTRAL were searched for randomized controlled trials and crossover studies until September 2024. The analysis included T1D adolescents and adults treated with low-dose glucagon versus nonglucagon treatments. Studies with glucagon-like peptides, noninsulin combinations, or uncontrolled exercise settings were excluded. Two authors extracted the data. The methodological quality was assessed with the Risk of Bias-2 tool and Grading of Recommendations Assessment, Development and Evaluations framework. Risk of Bias 2 informed a sensitivity analysis. The meta-analysis employed a random effects model to estimate the pooled treatment effects on hypoglycemia and time below range (TBR) (glucose <3.9 mmol/L), as well as secondary outcomes and adverse effects. RESULTS Of 6,792 records, 12 studies involving 248 individuals (mean age: 36 ± 10.5 years) met inclusion criteria. The meta-analysis showed significant reductions in hypoglycemia risk (risk ratio 0.54; 95% CI 0.35, 0.84) and TBR (−3.91 percentage points; 95% CI −6.27, 1.54) with low-dose glucagon. Sensitivity analysis yielded a slightly more confident effect size for hypoglycemia and TBR. However, overall adverse events increased with low-dose glucagon (risk ratio 2.75; 95% CI 1.07, 7.08). The included studies were few and heterogeneous, which may have influenced the overall outcomes. CONCLUSIONS Low-dose glucagon reduces exercise-induced hypoglycemia and TBR in T1D individuals. Future research should optimize glucagon dosage and timing for various exercise types and durations to confirm real-world effectiveness.
1型糖尿病（T1D）患者由于低血糖风险而难以控制运动。研究设计和方法本系统综述和荟萃分析评价了低剂量胰高血糖素预防和治疗T1D运动性低血糖的疗效。Medline、Embase和Cochrane CENTRAL检索了截至2024年9月的随机对照试验和交叉研究。该分析包括接受低剂量胰高血糖素与非胰高血糖素治疗的T1D青少年和成人。胰高血糖素样肽、非胰岛素组合或不受控制的运动设置的研究被排除在外。两位作者提取了这些数据。采用偏倚风险-2工具和建议分级评估、发展和评估框架对方法学质量进行评估。偏倚风险为2，进行敏感性分析。meta分析采用随机效应模型估计低血糖和低于范围时间（TBR）（葡萄糖&；lt;3.9 mmol/L）的综合治疗效果，以及次要结局和不良反应。结果在6792份记录中，12项研究涉及248名个体（平均年龄：36±10.5岁）符合纳入标准。荟萃分析显示，低剂量胰高血糖素显著降低了低血糖风险（风险比0.54;95% CI 0.35, 0.84）和TBR（- 3.91个百分点；95% CI - 6.27, 1.54）。敏感性分析对低血糖和TBR产生了更有信心的效应值。然而，低剂量胰高血糖素组总体不良事件增加（风险比2.75;95% CI 1.07, 7.08）。纳入的研究较少且异质性，这可能影响了总体结果。结论：低剂量胰高血糖素可降低T1D患者运动性低血糖和TBR。未来的研究应该优化各种运动类型和持续时间的胰高血糖素剂量和时间，以确认实际效果。
{"title":"Low-Dose Glucagon to Prevent and Treat Exercise-Associated Hypoglycemia in Individuals With Type 1 Diabetes: A Systematic Review and Meta-analysis","authors":"Sissel Banner Lundemose, Ajenthen Gayathri Ranjan, Ole Nørgaard, Tommi Suvitaival, Kirsten Nørgaard","doi":"10.2337/dc25-0702","DOIUrl":"https://doi.org/10.2337/dc25-0702","url":null,"abstract":"OBJECTIVE People with type 1 diabetes (T1D) struggle to manage exercise because of hypoglycemia risk. RESEARCH DESIGN AND METHODS This systematic review and meta-analysis evaluated low-dose glucagon's efficacy for preventing and treating exercise-induced hypoglycemia in T1D. Medline, Embase, and Cochrane CENTRAL were searched for randomized controlled trials and crossover studies until September 2024. The analysis included T1D adolescents and adults treated with low-dose glucagon versus nonglucagon treatments. Studies with glucagon-like peptides, noninsulin combinations, or uncontrolled exercise settings were excluded. Two authors extracted the data. The methodological quality was assessed with the Risk of Bias-2 tool and Grading of Recommendations Assessment, Development and Evaluations framework. Risk of Bias 2 informed a sensitivity analysis. The meta-analysis employed a random effects model to estimate the pooled treatment effects on hypoglycemia and time below range (TBR) (glucose &lt;3.9 mmol/L), as well as secondary outcomes and adverse effects. RESULTS Of 6,792 records, 12 studies involving 248 individuals (mean age: 36 ± 10.5 years) met inclusion criteria. The meta-analysis showed significant reductions in hypoglycemia risk (risk ratio 0.54; 95% CI 0.35, 0.84) and TBR (−3.91 percentage points; 95% CI −6.27, 1.54) with low-dose glucagon. Sensitivity analysis yielded a slightly more confident effect size for hypoglycemia and TBR. However, overall adverse events increased with low-dose glucagon (risk ratio 2.75; 95% CI 1.07, 7.08). The included studies were few and heterogeneous, which may have influenced the overall outcomes. CONCLUSIONS Low-dose glucagon reduces exercise-induced hypoglycemia and TBR in T1D individuals. Future research should optimize glucagon dosage and timing for various exercise types and durations to confirm real-world effectiveness.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"46 1","pages":"1637-1645"},"PeriodicalIF":16.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christine Ljungberg, Mette Nørgaard, Christina Vandenbroucke-Grauls, Jakob Kristian Jakobsen, Morten Haaning Charles, Anton Pottegård, Michael Dalager-Pedersen, Henrik Toft Sørensen, Reimar Wernich Thomsen
OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) induce glucosuria, potentially leading to infection and inflammation in the preputial microenvironment, subsequently increasing the risk of phimosis. We aimed to investigate the risks of phimosis in males with type 2 diabetes initiating SGLT2i or glucagon-like peptide-1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS In this population-based active-comparator new-user cohort study emulating a target trial, we included all adult male metformin users in Denmark initiating SGLT2i or GLP-1RA between 2016 and 2021. We used inverse probability of treatment weighting to balance the distribution of potential confounders. We estimated weighted intention-to-treat risk and risk ratios of phimosis identified from population-based medical databases. RESULTS In this study, we included 32,486 SGLT2i initiators and 14,793 GLP-1RA initiators with a median follow-up of 4 years (maximum 8 years). The risk of phimosis was elevated among SGLT2i users. The 1-year risk of phimosis was 0.9% among new SGLT2i users and 0.5% among new GLP-1RA users, corresponding to a 1-year risk ratio of 1.88 (95% CI, 1.43 to 2.47). During 8 years of follow-up, the risk of phimosis accumulated up to 4.8% in SGLT2i users and 3.6% in GLP-1RA users, with an 8-year risk ratio of 1.36 (95% CI, 1.14 to 1.61). CONCLUSIONS SGLT2i use was associated with a nearly twofold increased phimosis risk 1 year after treatment initiation in men with type 2 diabetes, compared with GLP-1RA use. Over 8 years of follow-up, the risk remained elevated, indicating a persistently higher risk associated with SGLT2i use.
{"title":"Risk of Phimosis Associated With SGLT2i Versus GLP-1RA: A Danish Cohort Study","authors":"Christine Ljungberg, Mette Nørgaard, Christina Vandenbroucke-Grauls, Jakob Kristian Jakobsen, Morten Haaning Charles, Anton Pottegård, Michael Dalager-Pedersen, Henrik Toft Sørensen, Reimar Wernich Thomsen","doi":"10.2337/dc25-0693","DOIUrl":"https://doi.org/10.2337/dc25-0693","url":null,"abstract":"OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) induce glucosuria, potentially leading to infection and inflammation in the preputial microenvironment, subsequently increasing the risk of phimosis. We aimed to investigate the risks of phimosis in males with type 2 diabetes initiating SGLT2i or glucagon-like peptide-1 receptor agonists (GLP-1RA). RESEARCH DESIGN AND METHODS In this population-based active-comparator new-user cohort study emulating a target trial, we included all adult male metformin users in Denmark initiating SGLT2i or GLP-1RA between 2016 and 2021. We used inverse probability of treatment weighting to balance the distribution of potential confounders. We estimated weighted intention-to-treat risk and risk ratios of phimosis identified from population-based medical databases. RESULTS In this study, we included 32,486 SGLT2i initiators and 14,793 GLP-1RA initiators with a median follow-up of 4 years (maximum 8 years). The risk of phimosis was elevated among SGLT2i users. The 1-year risk of phimosis was 0.9% among new SGLT2i users and 0.5% among new GLP-1RA users, corresponding to a 1-year risk ratio of 1.88 (95% CI, 1.43 to 2.47). During 8 years of follow-up, the risk of phimosis accumulated up to 4.8% in SGLT2i users and 3.6% in GLP-1RA users, with an 8-year risk ratio of 1.36 (95% CI, 1.14 to 1.61). CONCLUSIONS SGLT2i use was associated with a nearly twofold increased phimosis risk 1 year after treatment initiation in men with type 2 diabetes, compared with GLP-1RA use. Over 8 years of follow-up, the risk remained elevated, indicating a persistently higher risk associated with SGLT2i use.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"19 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yilin Yoshida, Ngoc Quynh Nguyen, Eun Hye Moon, Casey Rebholz, Hicham Skali, Victoria Arthur, Justin B. Echouffo-Tcheugui, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J. Rodriguez, Qibin Qi, Susan Cheng, Bing Yu
OBJECTIVE Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals. RESEARCH DESIGN AND METHODS We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011–2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c >5.7%, fasting glucose >100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, defined according to echocardiographic abnormalities (left ventricular hypertrophy, systolic or diastolic dysfunction) or elevated NT-proBNP or troponin T, in two glycemic groups separately. We used Cox regression for prospective association between cardiac dysfunction–related metabolites identified in the prior step and HF risk, adjusting for clinical risk factors. Analyses were replicated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n = 5,167). RESULTS Microvascular disease–related metabolites (e.g., pseudouridine, N6-carbamoylthreonyladenosine, N6-acetyllysine, N2,N5-diacetylornithine) were associated with cardiac dysfunction in hyperglycemic individuals. Carbohydrate and cofactor-derived metabolites (e.g., gulonate, erythrocyte) were associated with cardiac dysfunction in euglycemic individuals. These cardiac dysfunction–related metabolites were prospectively associated with HF risk in the two glycemic groups (follow-up 7.5 years, 137 and 94 HF cases, per-SD increase hazards ratios range 1–1.9 and 1.1–2.9), respectively. HCHS/SOL results were consistent with those from ARIC. CONCLUSIONS Metabolites known for microvascular complications were associated with cardiac dysfunction in hyperglycemic individuals but not among their euglycemic counterparts, supporting the premise that microvascular dysfunction contributes to HF pathogenesis in diabetes.
{"title":"A Metabolomics Study of Cardiac Dysfunction in Hyperglycemia—Findings From the Atherosclerosis Risk in Communities (ARIC) Study and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)","authors":"Yilin Yoshida, Ngoc Quynh Nguyen, Eun Hye Moon, Casey Rebholz, Hicham Skali, Victoria Arthur, Justin B. Echouffo-Tcheugui, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J. Rodriguez, Qibin Qi, Susan Cheng, Bing Yu","doi":"10.2337/dc25-0730","DOIUrl":"https://doi.org/10.2337/dc25-0730","url":null,"abstract":"OBJECTIVE Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals. RESEARCH DESIGN AND METHODS We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011–2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c &gt;5.7%, fasting glucose &gt;100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, defined according to echocardiographic abnormalities (left ventricular hypertrophy, systolic or diastolic dysfunction) or elevated NT-proBNP or troponin T, in two glycemic groups separately. We used Cox regression for prospective association between cardiac dysfunction–related metabolites identified in the prior step and HF risk, adjusting for clinical risk factors. Analyses were replicated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n = 5,167). RESULTS Microvascular disease–related metabolites (e.g., pseudouridine, N6-carbamoylthreonyladenosine, N6-acetyllysine, N2,N5-diacetylornithine) were associated with cardiac dysfunction in hyperglycemic individuals. Carbohydrate and cofactor-derived metabolites (e.g., gulonate, erythrocyte) were associated with cardiac dysfunction in euglycemic individuals. These cardiac dysfunction–related metabolites were prospectively associated with HF risk in the two glycemic groups (follow-up 7.5 years, 137 and 94 HF cases, per-SD increase hazards ratios range 1–1.9 and 1.1–2.9), respectively. HCHS/SOL results were consistent with those from ARIC. CONCLUSIONS Metabolites known for microvascular complications were associated with cardiac dysfunction in hyperglycemic individuals but not among their euglycemic counterparts, supporting the premise that microvascular dysfunction contributes to HF pathogenesis in diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"50 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren A. Vanderlinden, Ellen Wong, Randi K. Johnson, Patrick Carry, Fran Dong, Katerina Kechris, Marian Rewers, Jill M. Norris
OBJECTIVE Multiple studies have reported an inverse association between self-reported smoking during pregnancy and offspring type 1 diabetes (T1D) risk. We investigated the association between DNA methylation (DNAm) smoke exposure scores, parental self-reported smoking, and islet autoimmunity (IA) and T1D risk in children at high risk of T1D. RESEARCH DESIGN AND METHODS We used longitudinal data from the Diabetes Autoimmunity Study in the Young cohort, including 205 IA case and 206 control participants (87 and 88 were T1D case and control participants, respectively), matched by age, race/ethnicity, and sample availability. DNAm profiles were obtained from cord or peripheral blood using the Infinium Human Methylation 450K or EPIC BeadChip. Three published DNAm smoking scores were calculated at every time point. To estimate in utero smoke exposure, participant-specific intercepts were derived from mixed-effects models of longitudinal DNAm scores. These intercepts strongly correlated with cord blood scores (r = 0.85–0.95; n = 179), indicating their utility as proxies for in utero smoke exposure. Associations with IA/T1D were evaluated using logistic regression, adjusting for HLA-DR3/4, first-degree relative status, and sex. RESULTS Multivariable models showed both maternally reported smoking during pregnancy and higher DNAm smoking scores to be associated with lower risk of IA and T1D. Maternal smoking showed a strong inverse association with IA (odds ratio [OR] 0.24; 95% CI 0.10–0.54). Rauschert and McCartney DNAm scores showed consistent inverse associations with both outcomes (OR 0.65–0.83 for SD increase). CONCLUSIONS Our study supports existing literature indicating in utero smoke exposure is associated with reduced IA and T1D risk. Further research is essential to uncover the underlying mechanisms.
目的：多项研究报道了妊娠期间自我报告吸烟与后代1型糖尿病（T1D）风险之间的负相关关系。我们调查了DNA甲基化（DNAm）烟雾暴露评分、父母自我报告吸烟、胰岛自身免疫（IA）和T1D高风险儿童T1D风险之间的关系。研究设计和方法我们使用了来自年轻队列糖尿病自身免疫研究的纵向数据，包括205例IA患者和206例对照受试者（分别为87例和88例T1D患者和对照受试者），根据年龄、种族/民族和样本可用性进行匹配。使用Infinium Human Methylation 450K或EPIC BeadChip从脐带或外周血中获得dna谱。在每个时间点计算三个公布的DNAm吸烟评分。为了估计子宫内的烟雾暴露，参与者特定的拦截来自纵向DNAm评分的混合效应模型。这些截距与脐带血评分密切相关(r = 0.85-0.95；N = 179)，表明它们作为子宫内烟雾暴露的代理的效用。在调整HLA-DR3/4、一级相对地位和性别后，采用logistic回归评估IA/T1D的相关性。结果多变量模型显示，母亲在怀孕期间报告吸烟和较高的DNAm吸烟评分与较低的IA和T1D风险相关。母亲吸烟与IA呈强烈的负相关(优势比[OR] 0.24；95% ci 0.10-0.54)。Rauschert和McCartney DNAm评分与两种结果呈一致的负相关（SD增加的OR为0.65-0.83）。结论：我们的研究支持现有文献，表明子宫内吸烟暴露与IA和T1D风险降低相关。进一步的研究对于揭示潜在的机制至关重要。
{"title":"DNA Methylation Smoking Scores and Risk of Islet Autoimmunity and Type 1 Diabetes","authors":"Lauren A. Vanderlinden, Ellen Wong, Randi K. Johnson, Patrick Carry, Fran Dong, Katerina Kechris, Marian Rewers, Jill M. Norris","doi":"10.2337/dc25-0330","DOIUrl":"https://doi.org/10.2337/dc25-0330","url":null,"abstract":"OBJECTIVE Multiple studies have reported an inverse association between self-reported smoking during pregnancy and offspring type 1 diabetes (T1D) risk. We investigated the association between DNA methylation (DNAm) smoke exposure scores, parental self-reported smoking, and islet autoimmunity (IA) and T1D risk in children at high risk of T1D. RESEARCH DESIGN AND METHODS We used longitudinal data from the Diabetes Autoimmunity Study in the Young cohort, including 205 IA case and 206 control participants (87 and 88 were T1D case and control participants, respectively), matched by age, race/ethnicity, and sample availability. DNAm profiles were obtained from cord or peripheral blood using the Infinium Human Methylation 450K or EPIC BeadChip. Three published DNAm smoking scores were calculated at every time point. To estimate in utero smoke exposure, participant-specific intercepts were derived from mixed-effects models of longitudinal DNAm scores. These intercepts strongly correlated with cord blood scores (r = 0.85–0.95; n = 179), indicating their utility as proxies for in utero smoke exposure. Associations with IA/T1D were evaluated using logistic regression, adjusting for HLA-DR3/4, first-degree relative status, and sex. RESULTS Multivariable models showed both maternally reported smoking during pregnancy and higher DNAm smoking scores to be associated with lower risk of IA and T1D. Maternal smoking showed a strong inverse association with IA (odds ratio [OR] 0.24; 95% CI 0.10–0.54). Rauschert and McCartney DNAm scores showed consistent inverse associations with both outcomes (OR 0.65–0.83 for SD increase). CONCLUSIONS Our study supports existing literature indicating in utero smoke exposure is associated with reduced IA and T1D risk. Further research is essential to uncover the underlying mechanisms.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"27 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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