South Asia has high prevalence rates of type 2 diabetes (T2D). Until the 1990s, the prevalence of T2D within South Asia was low but much higher in the South Asian diaspora living abroad. Today, high prevalence rates of T2D are reported among those living in South Asia. T2D in South Asians presents with unique clinical features described as the “South Asian phenotype” that include younger age at onset of diabetes than in White Europeans, much lower BMI, hyperinsulinemia and greater insulin resistance, rapid decline in β-cell function resulting in low insulin reserve, low muscle mass, and greater ectopic fat deposition, especially in the liver. Also, prevalence of impaired fasting glucose is higher among South Asians than prevalence of impaired glucose tolerance. Genetic predisposition combined with intrauterine fetal programming (low vitamin B12 intake and high folate intake) increases susceptibility to T2D, from birth. In later life, overnutrition, especially a high carbohydrate intake with refined grains of higher glycemic index, coupled with low physical activity likely triggers the T2D epidemic in South Asians. Additionally, there are emerging risk factors like air pollution. Preventing T2D in South Asians requires a multifactorial approach, including improvements in maternal and fetal nutrition with special reference to vitamin B12 and folate intake, decreasing refined carbohydrate and increasing protein and fiber intake in the diet, increasing physical activity, and control of air pollution. Lessons learned from epidemiology of T2D in South Asians could be useful to other developing countries that are in earlier stages of epidemiological transition.
{"title":"Lessons Learned From Epidemiology of Type 2 Diabetes in South Asians: Kelly West Award Lecture 2024","authors":"Viswanathan Mohan","doi":"10.2337/dci24-0046","DOIUrl":"https://doi.org/10.2337/dci24-0046","url":null,"abstract":"South Asia has high prevalence rates of type 2 diabetes (T2D). Until the 1990s, the prevalence of T2D within South Asia was low but much higher in the South Asian diaspora living abroad. Today, high prevalence rates of T2D are reported among those living in South Asia. T2D in South Asians presents with unique clinical features described as the “South Asian phenotype” that include younger age at onset of diabetes than in White Europeans, much lower BMI, hyperinsulinemia and greater insulin resistance, rapid decline in β-cell function resulting in low insulin reserve, low muscle mass, and greater ectopic fat deposition, especially in the liver. Also, prevalence of impaired fasting glucose is higher among South Asians than prevalence of impaired glucose tolerance. Genetic predisposition combined with intrauterine fetal programming (low vitamin B12 intake and high folate intake) increases susceptibility to T2D, from birth. In later life, overnutrition, especially a high carbohydrate intake with refined grains of higher glycemic index, coupled with low physical activity likely triggers the T2D epidemic in South Asians. Additionally, there are emerging risk factors like air pollution. Preventing T2D in South Asians requires a multifactorial approach, including improvements in maternal and fetal nutrition with special reference to vitamin B12 and folate intake, decreasing refined carbohydrate and increasing protein and fiber intake in the diet, increasing physical activity, and control of air pollution. Lessons learned from epidemiology of T2D in South Asians could be useful to other developing countries that are in earlier stages of epidemiological transition.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"14 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020558","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}
Hon Jen Wong, Bryan Sim, Yao Hao Teo, Yao Neng Teo, Mark Y. Chan, Leonard L.L. Yeo, Pei Chia Eng, Benjamin Y.Q. Tan, Naveed Sattar, Mayank Dalakoti, Ching-Hui Sia
OBJECTIVE To provide an updated synthesis on effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on weight, BMI, and waist circumference incorporating newer randomized controlled trials (RCTs), particularly in individuals with overweight or obesity. RESEARCH DESIGN AND METHODS We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published from inception to 4 October 2024. The search was limited to RCTs evaluating the use of GLP-1 RAs for mean differences from baseline in weight, BMI, and waist circumference in adults with obesity or overweight with or without diabetes. Two independent reviewers performed the literature search and data extraction, resolving disagreements via consensus or third-reviewer consultation. RESULTS Forty-seven RCTs were included, with a combined cohort of 23,244 patients. GLP-1 RAs demonstrated a mean weight reduction of −4.57 kg (95% CI −5.35 to −3.78), mean BMI reduction of −2.07 kg/m2 (95% CI −2.53 to −1.62), and mean waist circumference reduction of −4.55 cm (95% CI −5.72 to −3.38) compared with placebo. This effect was consistent across diabetes status, GLP-1 RA used, and route of administration. The greatest treatment benefit appeared to favor patients who were younger, female, without diabetes, with higher baseline weight and BMI but lower baseline HbA1c, and treated over a longer duration. Limitations include substantial statistical heterogeneity, in part due to broad inclusion criteria. However, this heterogeneity may improve generalizability by reflecting a wide range of study designs and patient populations. CONCLUSIONS GLP-1 RAs demonstrated significant weight, BMI, and waist circumference reduction benefits in this meta-analysis.
目的：通过最新的随机对照试验（rct），特别是在超重或肥胖人群中，提供胰高血糖素样肽1受体激动剂（GLP-1 RAs）对体重、BMI和腰围影响的最新合成。研究设计和方法我们系统地检索PubMed、Embase和Cochrane Central Register of Controlled Trials (Central)，检索从成立到2024年10月4日发表的随机对照试验。该研究仅限于评估GLP-1 RAs在肥胖或超重伴或不伴糖尿病的成人中与基线体重、BMI和腰围的平均差异的随机对照试验。两位独立的审稿人进行文献检索和数据提取，通过共识或第三方审稿人咨询来解决分歧。结果纳入47项随机对照试验，共纳入23,244例患者。与安慰剂相比，GLP-1 RAs显示平均体重减轻- 4.57 kg (95% CI - 5.35至- 3.78)，平均BMI减少- 2.07 kg/m2 (95% CI - 2.53至- 1.62)，平均腰围减少- 4.55 cm （95% CI - 5.72至- 3.38）。这种效果在糖尿病状态、GLP-1 RA的使用和给药途径中是一致的。最大的治疗效果似乎有利于年轻、女性、无糖尿病、基线体重和BMI较高但基线HbA1c较低、治疗时间较长的患者。局限性包括大量的统计异质性，部分原因是由于广泛的纳入标准。然而，这种异质性可以通过反映广泛的研究设计和患者群体来提高通用性。结论：在这项荟萃分析中，GLP-1 RAs显示出显著的体重、BMI和腰围降低益处。
{"title":"Efficacy of GLP-1 Receptor Agonists on Weight Loss, BMI, and Waist Circumference for Patients With Obesity or Overweight: A Systematic Review, Meta-analysis, and Meta-regression of 47 Randomized Controlled Trials","authors":"Hon Jen Wong, Bryan Sim, Yao Hao Teo, Yao Neng Teo, Mark Y. Chan, Leonard L.L. Yeo, Pei Chia Eng, Benjamin Y.Q. Tan, Naveed Sattar, Mayank Dalakoti, Ching-Hui Sia","doi":"10.2337/dc24-1678","DOIUrl":"https://doi.org/10.2337/dc24-1678","url":null,"abstract":"OBJECTIVE To provide an updated synthesis on effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on weight, BMI, and waist circumference incorporating newer randomized controlled trials (RCTs), particularly in individuals with overweight or obesity. RESEARCH DESIGN AND METHODS We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published from inception to 4 October 2024. The search was limited to RCTs evaluating the use of GLP-1 RAs for mean differences from baseline in weight, BMI, and waist circumference in adults with obesity or overweight with or without diabetes. Two independent reviewers performed the literature search and data extraction, resolving disagreements via consensus or third-reviewer consultation. RESULTS Forty-seven RCTs were included, with a combined cohort of 23,244 patients. GLP-1 RAs demonstrated a mean weight reduction of −4.57 kg (95% CI −5.35 to −3.78), mean BMI reduction of −2.07 kg/m2 (95% CI −2.53 to −1.62), and mean waist circumference reduction of −4.55 cm (95% CI −5.72 to −3.38) compared with placebo. This effect was consistent across diabetes status, GLP-1 RA used, and route of administration. The greatest treatment benefit appeared to favor patients who were younger, female, without diabetes, with higher baseline weight and BMI but lower baseline HbA1c, and treated over a longer duration. Limitations include substantial statistical heterogeneity, in part due to broad inclusion criteria. However, this heterogeneity may improve generalizability by reflecting a wide range of study designs and patient populations. CONCLUSIONS GLP-1 RAs demonstrated significant weight, BMI, and waist circumference reduction benefits in this meta-analysis.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"12 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020559","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}
Michael E. Bowen, Ildiko Lingvay, Luigi Meneghini, Brett Moran, Noel O. Santini, Song Zhang, Ethan A. Halm
OBJECTIVE We derive and validate D-RISK, an electronic health record (EHR)-driven risk score to optimize and facilitate screening for undiagnosed dysglycemia (prediabetes + diabetes) in clinical practice. RESEARCH DESIGN AND METHODS We used retrospective EHR data (derivation sample) and a prospective diabetes screening study (validation sample) to develop D-RISK. Logistic regression with backward selection was used to predict dysglycemia (HbA1c ≥5.7%) using diabetes risk factors consistently captured in structured EHR data. Model coefficients were converted to a points-based risk score. We report discrimination, sensitivity, and specificity and compare D-RISK to the American Diabetes Association (ADA) risk test and the ADA and United States Preventive Services Task Force (USPSTF) screening guidelines. RESULTS The derivation cohort included 11,387 patients (mean age 48 years; 65% female; 42% Hispanic; 32% non-Hispanic Black; mean BMI 32; 29% with hypertension). D-RISK included age, race, BMI, hypertension, and random glucose. The area under curve (AUC) for the risk score was 0.75 (95% CI 0.74–0.76). In the validation screening study (n = 519), the AUC was 0.71 (95% CI 0.66–0.75) which was better than the ADA and USPSTF diabetes screening guidelines (AUC = 0.52 and AUC = 0.58, respectively; P < 0.001 for both). Discrimination was similar to the ADA risk test (AUC = 0.67) using patient-reported data to supplement EHR data, although D-RISK was more sensitive (75% vs. 61%) at the recommended screening thresholds. CONCLUSIONS Designed for use in EHR, D-RISK performs better than commonly used screening guidelines and risk scores and may help detect undiagnosed cases of dysglycemia in clinical practice.
我们推导并验证了电子健康记录（EHR）驱动的风险评分D-RISK，以优化和促进临床实践中未确诊的血糖异常（前驱糖尿病+糖尿病）的筛查。研究设计和方法我们使用回顾性电子病历数据（衍生样本）和前瞻性糖尿病筛查研究（验证样本）来研究D-RISK。利用结构化电子病历数据中一致捕获的糖尿病危险因素，采用Logistic回归和逆向选择预测血糖异常（HbA1c≥5.7%）。将模型系数转换为基于点数的风险评分。我们报告了区别、敏感性和特异性，并将D-RISK与美国糖尿病协会（ADA）风险测试、ADA和美国预防服务工作组（USPSTF）筛查指南进行了比较。结果衍生队列包括11,387例患者(平均年龄48岁；65%的女性;42%的西班牙裔;32%是非西班牙裔黑人；平均BMI为32；29%为高血压)。D-RISK包括年龄、种族、BMI、高血压和随机血糖。风险评分的曲线下面积（AUC）为0.75 （95% CI 0.74-0.76）。在验证筛选研究（n = 519）中，AUC为0.71 (95% CI 0.66-0.75)，优于ADA和USPSTF糖尿病筛查指南(AUC分别为0.52和0.58；P, lt;两者均为0.001)。使用患者报告数据来补充电子病历数据的辨别性与ADA风险测试相似（AUC = 0.67），尽管D-RISK在推荐的筛查阈值下更敏感（75%对61%）。结论：设计用于电子病历的D-RISK比常用的筛查指南和风险评分效果更好，可能有助于在临床实践中发现未确诊的血糖异常病例。
{"title":"Derivation and Validation of D-RISK: An Electronic Health Record–Driven Risk Score to Detect Undiagnosed Dysglycemia in Clinical Practice","authors":"Michael E. Bowen, Ildiko Lingvay, Luigi Meneghini, Brett Moran, Noel O. Santini, Song Zhang, Ethan A. Halm","doi":"10.2337/dc24-1624","DOIUrl":"https://doi.org/10.2337/dc24-1624","url":null,"abstract":"OBJECTIVE We derive and validate D-RISK, an electronic health record (EHR)-driven risk score to optimize and facilitate screening for undiagnosed dysglycemia (prediabetes + diabetes) in clinical practice. RESEARCH DESIGN AND METHODS We used retrospective EHR data (derivation sample) and a prospective diabetes screening study (validation sample) to develop D-RISK. Logistic regression with backward selection was used to predict dysglycemia (HbA1c ≥5.7%) using diabetes risk factors consistently captured in structured EHR data. Model coefficients were converted to a points-based risk score. We report discrimination, sensitivity, and specificity and compare D-RISK to the American Diabetes Association (ADA) risk test and the ADA and United States Preventive Services Task Force (USPSTF) screening guidelines. RESULTS The derivation cohort included 11,387 patients (mean age 48 years; 65% female; 42% Hispanic; 32% non-Hispanic Black; mean BMI 32; 29% with hypertension). D-RISK included age, race, BMI, hypertension, and random glucose. The area under curve (AUC) for the risk score was 0.75 (95% CI 0.74–0.76). In the validation screening study (n = 519), the AUC was 0.71 (95% CI 0.66–0.75) which was better than the ADA and USPSTF diabetes screening guidelines (AUC = 0.52 and AUC = 0.58, respectively; P &lt; 0.001 for both). Discrimination was similar to the ADA risk test (AUC = 0.67) using patient-reported data to supplement EHR data, although D-RISK was more sensitive (75% vs. 61%) at the recommended screening thresholds. CONCLUSIONS Designed for use in EHR, D-RISK performs better than commonly used screening guidelines and risk scores and may help detect undiagnosed cases of dysglycemia in clinical practice.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"11 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988461","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}
Leonard E. Egede, Jennifer A. Campbell, Sebastian Linde, Rebekah J. Walker
The objective of this review is to evaluate and summarize the evidence base for the effects of monetary intervention approaches (the use of positive monetary reinforcers and gains) on diabetes outcomes. A reproducible search using OVID Medline, PubMed, Scopus, and CINAHL was conducted. Articles published from database creation up to July 2024 were searched. Outcomes included hemoglobin A1c (HbA1c), LDL, BMI, blood pressure, quality of life (QOL), psychosocial factors, self-care behaviors, and diabetes complications. A total of 13 articles met inclusion criteria and were included for final synthesis. Looking at the monetary approach across each study, eight used financial incentives, three used a form of income supplementation, one used cash transfers, and one used a combination of income supplementation and financial incentives. Ten of the 13 studies found statistically significant and clinically meaningful changes in HbA1c. For participants receiving interventions, change in HbA1c ranged from 0.19% to 1.74% for interventions incorporating financial incentives, 0.7% to 1.3% for interventions incorporating income supplementation, and 0.2% to 0.7% for the study incorporating cash transfers. Overall, evidence supports the relationship between monetary approaches, diabetes-related outcomes, and self-care behaviors across monetary approaches. Future studies should consider comparison between different monetary approaches using designs that will allow identification of effective strategies. As these approaches are theoretically and structurally different, pathways identifying the underlying mechanisms of change are greatly needed to advance the field.
{"title":"Financial Incentives, Income Supplementation, Cash Transfer, and Universal Basic Income Interventions in Diabetes: Understanding Differences and Effectiveness: A Scoping Review","authors":"Leonard E. Egede, Jennifer A. Campbell, Sebastian Linde, Rebekah J. Walker","doi":"10.2337/dci24-0072","DOIUrl":"https://doi.org/10.2337/dci24-0072","url":null,"abstract":"The objective of this review is to evaluate and summarize the evidence base for the effects of monetary intervention approaches (the use of positive monetary reinforcers and gains) on diabetes outcomes. A reproducible search using OVID Medline, PubMed, Scopus, and CINAHL was conducted. Articles published from database creation up to July 2024 were searched. Outcomes included hemoglobin A1c (HbA1c), LDL, BMI, blood pressure, quality of life (QOL), psychosocial factors, self-care behaviors, and diabetes complications. A total of 13 articles met inclusion criteria and were included for final synthesis. Looking at the monetary approach across each study, eight used financial incentives, three used a form of income supplementation, one used cash transfers, and one used a combination of income supplementation and financial incentives. Ten of the 13 studies found statistically significant and clinically meaningful changes in HbA1c. For participants receiving interventions, change in HbA1c ranged from 0.19% to 1.74% for interventions incorporating financial incentives, 0.7% to 1.3% for interventions incorporating income supplementation, and 0.2% to 0.7% for the study incorporating cash transfers. Overall, evidence supports the relationship between monetary approaches, diabetes-related outcomes, and self-care behaviors across monetary approaches. Future studies should consider comparison between different monetary approaches using designs that will allow identification of effective strategies. As these approaches are theoretically and structurally different, pathways identifying the underlying mechanisms of change are greatly needed to advance the field.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"52 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981448","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}
Ida M. Mynarek, Lars Krogvold, Freja B. Mørk, Trine W. H. Lawaetz, Trine Roald, Morten W. Fagerland, Nina Lindblom, Jacob Westman, Peter Barker, Heikki Hyöty, Johnny Ludvigsson, Kristian F. Hanssen, Jesper Johannesen, Knut Dahl-Jørgensen
OBJECTIVE In the Diabetes Virus Detection and Intervention trial, antiviral treatment with pleconaril and ribavirin decreased the decline, compared with placebo, in endogenous C-peptide 1 year after diagnosis of type 1 diabetes (T1D) in children and adolescents. This article reports the results 2 and 3 years after diagnosis. RESEARCH DESIGN AND METHODS This was a multicenter, randomized, placebo-controlled (1:1) trial of 96 children and adolescents aged 6–15.9 years newly diagnosed with T1D. Antiviral treatment (pleconaril and ribavirin) or placebo was given for 6 months from diagnosis, and participants were followed for 3 years. The primary outcome was residual C-peptide secretion, reported as the area under the curve (AUC), assessed by 2-h mixed-meal tolerance test. Secondary outcomes included insulin doses and HbA1c. RESULTS At the 3-year follow-up, 75 participants attended. At 2 years, the mean ± SD AUC for C-peptide in the placebo group was 0.27 ± 0.33 compared with 0.34 ± 0.37 in the pleconaril and ribavirin group. After 3 years, the AUC had decreased to 0.17 ± 0.23 and 0.25 ± 0.34, respectively. There was no statistically significant difference between the groups. The groups were also comparable with regard to secondary end points. CONCLUSIONS The decreased reduction in C-peptide levels after antiviral treatment is no longer present after 2 or 3 years. Further investigations are needed to explore options to use antiviral treatment in the prevention and treatment of T1D.
{"title":"Three-Year Follow-up After Antiviral Treatment in New-Onset Type 1 Diabetes: Results From the Diabetes Virus Detection and Intervention Trial","authors":"Ida M. Mynarek, Lars Krogvold, Freja B. Mørk, Trine W. H. Lawaetz, Trine Roald, Morten W. Fagerland, Nina Lindblom, Jacob Westman, Peter Barker, Heikki Hyöty, Johnny Ludvigsson, Kristian F. Hanssen, Jesper Johannesen, Knut Dahl-Jørgensen","doi":"10.2337/dc24-2121","DOIUrl":"https://doi.org/10.2337/dc24-2121","url":null,"abstract":"OBJECTIVE In the Diabetes Virus Detection and Intervention trial, antiviral treatment with pleconaril and ribavirin decreased the decline, compared with placebo, in endogenous C-peptide 1 year after diagnosis of type 1 diabetes (T1D) in children and adolescents. This article reports the results 2 and 3 years after diagnosis. RESEARCH DESIGN AND METHODS This was a multicenter, randomized, placebo-controlled (1:1) trial of 96 children and adolescents aged 6–15.9 years newly diagnosed with T1D. Antiviral treatment (pleconaril and ribavirin) or placebo was given for 6 months from diagnosis, and participants were followed for 3 years. The primary outcome was residual C-peptide secretion, reported as the area under the curve (AUC), assessed by 2-h mixed-meal tolerance test. Secondary outcomes included insulin doses and HbA1c. RESULTS At the 3-year follow-up, 75 participants attended. At 2 years, the mean ± SD AUC for C-peptide in the placebo group was 0.27 ± 0.33 compared with 0.34 ± 0.37 in the pleconaril and ribavirin group. After 3 years, the AUC had decreased to 0.17 ± 0.23 and 0.25 ± 0.34, respectively. There was no statistically significant difference between the groups. The groups were also comparable with regard to secondary end points. CONCLUSIONS The decreased reduction in C-peptide levels after antiviral treatment is no longer present after 2 or 3 years. Further investigations are needed to explore options to use antiviral treatment in the prevention and treatment of T1D.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"43 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974557","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}
Meredith E. Osmulski, Yuanzhi Yu, Alan Kuang, Jami L. Josefson, Marie-France Hivert, Denise M. Scholtens, William L. Lowe
OBJECTIVE Subtypes of gestational diabetes mellitus (GDM) based on insulin sensitivity and secretion have been described. We addressed the hypothesis that GDM subtypes are differentially associated with newborn and child anthropometric and glycemic outcomes. RESEARCH DESIGN AND METHODS Newborn and child (age 11–14 years) outcomes were examined in 7,970 and 4,160 mother-offspring dyads, respectively, who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study (HAPO) and Follow-Up Study. GDM was classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity), insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion), or mixed-defect GDM (both <25th percentile). Regression models for newborn and child outcomes included adjustment for field center, maternal BMI, and other pregnancy covariates. Child models also included adjustment for child age, sex, and family history of diabetes. RESULTS Compared with mothers with normal glucose tolerance, all three GDM subtypes were associated with birth weight and sum of skinfolds >90th percentile. Insulin-resistant and mixed-defect GDM were associated with higher risk of cord C-peptide levels >90th percentile. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia and childhood obesity (odds ratio [OR] 1.53, 95% CI 1.127–2.08). The risk of child-impaired glucose tolerance was higher with insulin-resistant (OR 2.21, 95% CI 1.50–3.25) and mixed-defect GDM (OR 3.01, 95% CI 1.47–6.19). CONCLUSIONS GDM subtypes are differentially associated with newborn and childhood outcomes. Better characterizing individuals with GDM could help identify at-risk offspring to offer targeted, preventative interventions early in life.
目的探讨基于胰岛素敏感性和胰岛素分泌的妊娠期糖尿病（GDM）亚型。我们提出了GDM亚型与新生儿和儿童人体测量和血糖结局存在差异的假设。研究设计和方法分别对参加高血糖和不良妊娠结局研究（HAPO）和随访研究的7,970和4,160对母子进行新生儿和儿童（11-14岁）结局检查。GDM分为胰岛素缺乏型GDM（胰岛素分泌&；lt；第25百分位，保留胰岛素敏感性）、胰岛素抵抗型GDM（胰岛素敏感&；lt；第25百分位，保留胰岛素分泌）或混合缺陷型GDM（两者均为&；lt；第25百分位）。新生儿和儿童结局的回归模型包括调整现场中心、母亲BMI和其他妊娠协变量。儿童模型还包括儿童年龄、性别和糖尿病家族史的调整。结果：与糖耐量正常的母亲相比，所有三种GDM亚型均与出生体重和皮肤皱褶总数（第90百分位数）相关。胰岛素抵抗和混合缺陷型GDM与脐带c肽水平升高的风险相关[amp；gt；90百分位数]。胰岛素抵抗型GDM与新生儿低血糖的高风险相关。胰岛素抵抗型GDM与新生儿低血糖和儿童肥胖的高风险相关（优势比[OR] 1.53, 95% CI 1.127-2.08）。胰岛素抵抗组（OR 2.21, 95% CI 1.50-3.25）和混合缺陷GDM组（OR 3.01, 95% CI 1.47-6.19）儿童糖耐量受损的风险更高。结论：GDM亚型与新生儿和儿童预后存在差异。更好地描述GDM患者的特征可以帮助识别有风险的后代，从而在生命早期提供有针对性的预防性干预。
{"title":"Subtypes of Gestational Diabetes Mellitus Are Differentially Associated With Newborn and Childhood Metabolic Outcomes","authors":"Meredith E. Osmulski, Yuanzhi Yu, Alan Kuang, Jami L. Josefson, Marie-France Hivert, Denise M. Scholtens, William L. Lowe","doi":"10.2337/dc24-1735","DOIUrl":"https://doi.org/10.2337/dc24-1735","url":null,"abstract":"OBJECTIVE Subtypes of gestational diabetes mellitus (GDM) based on insulin sensitivity and secretion have been described. We addressed the hypothesis that GDM subtypes are differentially associated with newborn and child anthropometric and glycemic outcomes. RESEARCH DESIGN AND METHODS Newborn and child (age 11–14 years) outcomes were examined in 7,970 and 4,160 mother-offspring dyads, respectively, who participated in the Hyperglycemia and Adverse Pregnancy Outcome Study (HAPO) and Follow-Up Study. GDM was classified as insulin-deficient GDM (insulin secretion &lt;25th percentile with preserved insulin sensitivity), insulin-resistant GDM (insulin sensitivity &lt;25th percentile with preserved insulin secretion), or mixed-defect GDM (both &lt;25th percentile). Regression models for newborn and child outcomes included adjustment for field center, maternal BMI, and other pregnancy covariates. Child models also included adjustment for child age, sex, and family history of diabetes. RESULTS Compared with mothers with normal glucose tolerance, all three GDM subtypes were associated with birth weight and sum of skinfolds &gt;90th percentile. Insulin-resistant and mixed-defect GDM were associated with higher risk of cord C-peptide levels &gt;90th percentile. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia and childhood obesity (odds ratio [OR] 1.53, 95% CI 1.127–2.08). The risk of child-impaired glucose tolerance was higher with insulin-resistant (OR 2.21, 95% CI 1.50–3.25) and mixed-defect GDM (OR 3.01, 95% CI 1.47–6.19). CONCLUSIONS GDM subtypes are differentially associated with newborn and childhood outcomes. Better characterizing individuals with GDM could help identify at-risk offspring to offer targeted, preventative interventions early in life.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"75 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939855","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 To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 (SGLT-2) inhibitors, separately, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with a reduced risk of cirrhosis and other adverse liver outcomes among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS With an active comparator, new-user approach, we conducted a cohort study using the U.K. Clinical Practice Research Datalink linked with hospital and national statistics databases. Cox proportional hazards models using propensity score fine stratification weighting were used to calculate hazard ratios (HRs) and 95% CIs for cirrhosis (primary outcome) and decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality (secondary outcomes). RESULTS In the first cohort comparing 25,516 patients starting GLP-1RAs and 186,752 starting DPP-4 inhibitors, GLP-1RAs were not associated with the incidence of cirrhosis (HR 0.90, 95% CI 0.68–1.19) or the secondary outcomes. In a separate cohort comparing 33,161 patients starting SGLT-2 inhibitors and 124,431 starting DPP-4 inhibitors, SGLT-2 inhibitors were associated with a reduced incidence of cirrhosis (HR 0.64, 95% CI 0.46–0.90), as also decompensated cirrhosis (HR 0.74, 95% CI 0.54–1.00), but not with a lower risk of hepatocellular carcinoma or liver-related mortality. CONCLUSIONS In patients with type 2 diabetes in the U.K., GLP-1RAs were not associated with a lower risk of cirrhosis compared with DPP-4 inhibitors in patients with type 2 diabetes. However, SGLT-2 inhibitors were associated with a lower risk of cirrhosis compared with DPP-4 inhibitors.
目的：研究胰高血糖素样肽1受体激动剂（GLP-1RAs）和钠-葡萄糖共转运蛋白2 （SGLT-2）抑制剂与二肽基肽酶4 （DPP-4）抑制剂相比，是否能降低2型糖尿病患者肝硬化和其他不良肝脏结局的风险。研究设计和方法采用主动比较、新用户方法，我们使用与医院和国家统计数据库相关联的英国临床实践研究数据链进行了一项队列研究。采用倾向评分精细分层加权的Cox比例风险模型计算肝硬化（主要结局）、失代偿性肝硬化、肝细胞癌和肝脏相关死亡率（次要结局）的风险比（hr）和95% ci。在第一个队列中，比较25,516名开始使用GLP-1RAs的患者和186,752名开始使用DPP-4抑制剂的患者，GLP-1RAs与肝硬化发生率（HR 0.90, 95% CI 0.68-1.19）或次要结局无关。在一个单独的队列中，比较了33,161名开始使用SGLT-2抑制剂和124,431名开始使用DPP-4抑制剂的患者，SGLT-2抑制剂与肝硬化发生率降低相关（HR 0.64, 95% CI 0.46-0.90），也与失代偿性肝硬化相关（HR 0.74, 95% CI 0.54-1.00），但与肝细胞癌或肝脏相关死亡风险降低无关。结论：在英国的2型糖尿病患者中，与DPP-4抑制剂相比，GLP-1RAs与2型糖尿病患者肝硬化风险降低无关。然而，与DPP-4抑制剂相比，SGLT-2抑制剂与较低的肝硬化风险相关。
{"title":"Glucagon-Like Peptide 1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors and the Prevention of Cirrhosis Among Patients With Type 2 Diabetes","authors":"Richeek Pradhan, Hui Yin, Sally Lu, Giada Sebastiani, Oriana Yu, Samy Suissa, Laurent Azoulay","doi":"10.2337/dc24-1903","DOIUrl":"https://doi.org/10.2337/dc24-1903","url":null,"abstract":"OBJECTIVE To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 (SGLT-2) inhibitors, separately, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with a reduced risk of cirrhosis and other adverse liver outcomes among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS With an active comparator, new-user approach, we conducted a cohort study using the U.K. Clinical Practice Research Datalink linked with hospital and national statistics databases. Cox proportional hazards models using propensity score fine stratification weighting were used to calculate hazard ratios (HRs) and 95% CIs for cirrhosis (primary outcome) and decompensated cirrhosis, hepatocellular carcinoma, and liver-related mortality (secondary outcomes). RESULTS In the first cohort comparing 25,516 patients starting GLP-1RAs and 186,752 starting DPP-4 inhibitors, GLP-1RAs were not associated with the incidence of cirrhosis (HR 0.90, 95% CI 0.68–1.19) or the secondary outcomes. In a separate cohort comparing 33,161 patients starting SGLT-2 inhibitors and 124,431 starting DPP-4 inhibitors, SGLT-2 inhibitors were associated with a reduced incidence of cirrhosis (HR 0.64, 95% CI 0.46–0.90), as also decompensated cirrhosis (HR 0.74, 95% CI 0.54–1.00), but not with a lower risk of hepatocellular carcinoma or liver-related mortality. CONCLUSIONS In patients with type 2 diabetes in the U.K., GLP-1RAs were not associated with a lower risk of cirrhosis compared with DPP-4 inhibitors in patients with type 2 diabetes. However, SGLT-2 inhibitors were associated with a lower risk of cirrhosis compared with DPP-4 inhibitors.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"479 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936933","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}
Arjana Begzati, Karla P. Godinez-Macias, Tao Long, Jeramie D. Watrous, Rafael Moranchel, Edward D. Kantz, Jaakko Tuomilehto, Aki S. Havulinna, Teemu J. Niiranen, Pekka Jousilahti, Veikko Salomaa, Bing Yu, Faye Norby, Casey M. Rebholz, Elizabeth Selvin, Elizabeth A. Winzeler, Susan Cheng, Mona Alotaibi, Ravi Goyal, Trey Ideker, Mohit Jain, Amit R. Majithia
OBJECTIVE Plasma metabolite profiling has uncovered several nonglycemic markers of incident type 2 diabetes (T2D). We investigated whether such biomarkers provide information about specific aspects of T2D etiology, such as impaired fasting glucose and impaired glucose tolerance, and whether their association with T2D risk varies by race. RESEARCH DESIGN AND METHODS Untargeted plasma metabolite profiling was performed of participants in the FINRISK 2002 cohort (n = 7,564). Cox regression modeling was conducted to identify metabolites associated with incident T2D during 14 years of follow-up. Metabolites were clustered into pathways using Gaussian graphical modeling. Clusters enriched for T2D biomarkers were further examined for covariation with fasting plasma glucose (FPG), 2-h postchallenge plasma glucose (2hPG), HbA1c, or fasting insulin. Validation analyses and tests of interaction with race were performed in the Atherosclerosis Risk in Communities study. RESULTS Two clusters of metabolites, representing diacylglycerols (DAGs) and phosphatidylcholines (PCs), contained the largest number of metabolite associations with incident T2D. DAGs associated with increased T2D incidence (hazard ratio [HR] 1.22; 95% CI 1.14–1.30) independent of FPG, HbA1c, and fasting insulin, but not 2hPG. PCs were inversely associated with T2D risk (HR 0.78; 95% CI 0.71–0.85) independent of FPG, 2hPG, HbA1c, and fasting insulin. No significant interaction between DAGs or PCs and race was observed. CONCLUSIONS Fasting DAGs may capture information regarding T2D risk similar to that represented by 2hPG; PCs may capture aspects of T2D etiology that differ from those represented by conventional biomarkers. The direction of effect and strength of DAG and PC associations with incident T2D are similar across European and African Americans.
目的：血浆代谢物分析揭示了2型糖尿病（T2D）的几个非血糖标志物。我们调查了这些生物标志物是否提供了关于T2D病因的特定方面的信息，如空腹血糖受损和糖耐量受损，以及它们与T2D风险的关联是否因种族而异。研究设计和方法对FINRISK 2002队列（n = 7564）的参与者进行非靶向血浆代谢物分析。在14年的随访中，采用Cox回归模型确定与T2D事件相关的代谢物。使用高斯图形建模将代谢物聚类成通路。进一步检测富含T2D生物标志物的簇与空腹血糖（FPG）、攻药后2小时血糖（2hPG）、糖化血红蛋白（HbA1c）或空腹胰岛素的共变。在社区动脉粥样硬化风险研究中进行了验证分析和与种族相互作用的测试。结果两类代谢物，即二酰基甘油（dag）和磷脂酰胆碱（PCs），与T2D事件相关的代谢物最多。与T2D发病率增加相关的dag(风险比[HR] 1.22；95% CI 1.14-1.30)与FPG、HbA1c和空腹胰岛素无关，但与2hPG无关。pc与T2D风险呈负相关(HR 0.78；95% CI 0.71-0.85)，与FPG、2hPG、HbA1c和空腹胰岛素无关。未观察到dag或pc与种族之间的显著相互作用。结论：空腹DAGs可能捕捉到类似于2hPG所代表的T2D风险信息；pc可以捕捉到与传统生物标志物不同的t2dm病因。在欧洲人和非裔美国人中，DAG和PC与T2D事件相关的影响方向和强度相似。
{"title":"Plasma Lipid Metabolites, Clinical Glycemic Predictors, and Incident Type 2 Diabetes","authors":"Arjana Begzati, Karla P. Godinez-Macias, Tao Long, Jeramie D. Watrous, Rafael Moranchel, Edward D. Kantz, Jaakko Tuomilehto, Aki S. Havulinna, Teemu J. Niiranen, Pekka Jousilahti, Veikko Salomaa, Bing Yu, Faye Norby, Casey M. Rebholz, Elizabeth Selvin, Elizabeth A. Winzeler, Susan Cheng, Mona Alotaibi, Ravi Goyal, Trey Ideker, Mohit Jain, Amit R. Majithia","doi":"10.2337/dc24-2266","DOIUrl":"https://doi.org/10.2337/dc24-2266","url":null,"abstract":"OBJECTIVE Plasma metabolite profiling has uncovered several nonglycemic markers of incident type 2 diabetes (T2D). We investigated whether such biomarkers provide information about specific aspects of T2D etiology, such as impaired fasting glucose and impaired glucose tolerance, and whether their association with T2D risk varies by race. RESEARCH DESIGN AND METHODS Untargeted plasma metabolite profiling was performed of participants in the FINRISK 2002 cohort (n = 7,564). Cox regression modeling was conducted to identify metabolites associated with incident T2D during 14 years of follow-up. Metabolites were clustered into pathways using Gaussian graphical modeling. Clusters enriched for T2D biomarkers were further examined for covariation with fasting plasma glucose (FPG), 2-h postchallenge plasma glucose (2hPG), HbA1c, or fasting insulin. Validation analyses and tests of interaction with race were performed in the Atherosclerosis Risk in Communities study. RESULTS Two clusters of metabolites, representing diacylglycerols (DAGs) and phosphatidylcholines (PCs), contained the largest number of metabolite associations with incident T2D. DAGs associated with increased T2D incidence (hazard ratio [HR] 1.22; 95% CI 1.14–1.30) independent of FPG, HbA1c, and fasting insulin, but not 2hPG. PCs were inversely associated with T2D risk (HR 0.78; 95% CI 0.71–0.85) independent of FPG, 2hPG, HbA1c, and fasting insulin. No significant interaction between DAGs or PCs and race was observed. CONCLUSIONS Fasting DAGs may capture information regarding T2D risk similar to that represented by 2hPG; PCs may capture aspects of T2D etiology that differ from those represented by conventional biomarkers. The direction of effect and strength of DAG and PC associations with incident T2D are similar across European and African Americans.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"35 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935024","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}
Arnaud D. Kaze, Alain G. Bertoni, Ervin R. Fox, Michael E. Hall, Robert J. Mentz, Jarett D. Berry, Justin B. Echouffo-Tcheugui
OBJECTIVE To assess the extent to which the concomitant presence of subclinical myocardial injury or stress and diabetes affects the risk of heart failure (HF) subtypes. RESEARCH DESIGN AND METHODS The Jackson Heart Study included Black adults, categorized based on diabetes status, high-sensitivity cardiac troponin I (hs-cTnI), and brain natriuretic peptide (BNP) levels. Subclinical myocardial injury was defined as hs-cTnI ≥4 ng/L in women and ≥6 ng/L in men, and subclinical myocardial stress as BNP ≥35 pg/mL. The study outcomes included incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). RESULTS Among 3,484 participants (mean age 54.6 years, 63.2% women, 22.3% with diabetes, 26.4% with subclinical myocardial injury, 9.4% with subclinical myocardial stress), 306 developed HF (151 HFpEF and 139 HFrEF) over 12 years. Compared with individuals with no diabetes and no subclinical myocardial injury at recruitment, participants with diabetes and subclinical myocardial injury had a higher HF risk (hazard ratio [HR] 3.84, 95% CI 2.60–5.66), HFpEF (HR 3.68, 95% CI 2.13–6.36), and HFrEF (HR 4.26, 95% CI 2.40–7.53). The HRs associated with the presence of diabetes and subclinical myocardial stress versus their joint absence were 4.03 (95% CI 2.50–6.51), 5.71 (95% CI 3.11–10.47), and 2.13 (95% CI 0.88–5.17) for HF, HFpEF, and HFrEF, respectively. There was no significant diabetes status and cardiac biomarkers interaction. CONCLUSIONS Both diabetes and subclinical myocardial damage significantly increase the risk of all HF types among Black individuals.
目的评估亚临床心肌损伤或应激和糖尿病同时存在对心衰（HF）亚型风险的影响程度。研究设计和方法Jackson心脏研究纳入黑人成人，根据糖尿病状态、高敏感性心肌肌钙蛋白I （hs-cTnI）和脑钠肽（BNP）水平进行分类。亚临床心肌损伤定义为女性hs-cTnI≥4 ng/L，男性≥6 ng/L；亚临床心肌应激定义为BNP≥35 pg/mL。研究结果包括突发HF、保留射血分数的HF （HFpEF）和降低射血分数的HF （HFrEF）。在3,484名参与者中（平均年龄54.6岁，63.2%为女性，22.3%患有糖尿病，26.4%患有亚临床心肌损伤，9.4%患有亚临床心肌应激），306名参与者在12年内发生HF（151例HFpEF和139例HFrEF）。与招募时无糖尿病和无亚临床心肌损伤的个体相比，糖尿病和亚临床心肌损伤的参与者有更高的HF风险（危险比[HR] 3.84, 95% CI 2.60-5.66）， HFpEF （HR 3.68, 95% CI 2.13-6.36）和HFrEF （HR 4.26, 95% CI 2.40-7.53）。在HF、HFpEF和HFrEF中，糖尿病和亚临床心肌压力与关节缺失相关的hr分别为4.03 （95% CI 2.50-6.51）、5.71 （95% CI 3.11-10.47）和2.13 （95% CI 0.88-5.17）。没有明显的糖尿病状态和心脏生物标志物相互作用。结论：糖尿病和亚临床心肌损伤均显著增加黑人发生所有HF类型的风险。
{"title":"Diabetes, Subclinical Myocardial Injury or Stress and Risk of Heart Failure Subtypes: The Jackson Heart Study","authors":"Arnaud D. Kaze, Alain G. Bertoni, Ervin R. Fox, Michael E. Hall, Robert J. Mentz, Jarett D. Berry, Justin B. Echouffo-Tcheugui","doi":"10.2337/dc24-0654","DOIUrl":"https://doi.org/10.2337/dc24-0654","url":null,"abstract":"OBJECTIVE To assess the extent to which the concomitant presence of subclinical myocardial injury or stress and diabetes affects the risk of heart failure (HF) subtypes. RESEARCH DESIGN AND METHODS The Jackson Heart Study included Black adults, categorized based on diabetes status, high-sensitivity cardiac troponin I (hs-cTnI), and brain natriuretic peptide (BNP) levels. Subclinical myocardial injury was defined as hs-cTnI ≥4 ng/L in women and ≥6 ng/L in men, and subclinical myocardial stress as BNP ≥35 pg/mL. The study outcomes included incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). RESULTS Among 3,484 participants (mean age 54.6 years, 63.2% women, 22.3% with diabetes, 26.4% with subclinical myocardial injury, 9.4% with subclinical myocardial stress), 306 developed HF (151 HFpEF and 139 HFrEF) over 12 years. Compared with individuals with no diabetes and no subclinical myocardial injury at recruitment, participants with diabetes and subclinical myocardial injury had a higher HF risk (hazard ratio [HR] 3.84, 95% CI 2.60–5.66), HFpEF (HR 3.68, 95% CI 2.13–6.36), and HFrEF (HR 4.26, 95% CI 2.40–7.53). The HRs associated with the presence of diabetes and subclinical myocardial stress versus their joint absence were 4.03 (95% CI 2.50–6.51), 5.71 (95% CI 3.11–10.47), and 2.13 (95% CI 0.88–5.17) for HF, HFpEF, and HFrEF, respectively. There was no significant diabetes status and cardiac biomarkers interaction. CONCLUSIONS Both diabetes and subclinical myocardial damage significantly increase the risk of all HF types among Black individuals.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"20 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935022","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}
Hancheng Yu, Jijuan Zhang, Frank Qian, Pang Yao, Kun Xu, Ping Wu, Rui Li, Zixin Qiu, Ruyi Li, Kai Zhu, Lin Li, Tingting Geng, Xuefeng Yu, Danpei Li, Yunfei Liao, An Pan, Gang Liu
OBJECTIVE Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction. RESEARCH DESIGN AND METHODS This cohort study included 1,859 individuals with T2D from the UK Biobank. Multivariable-adjusted Cox regression models were used to explore associations between 2,920 plasma proteins and incident PAD. Proteins were further selected as predictors using least absolute shrinkage and selection operator (LASSO) penalty. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, continuous/categorical net reclassification improvement, and integrated discrimination improvement. RESULTS Over a median follow-up of 13.2 years, 157 incident PAD cases occurred. We observed 463 proteins associated with PAD risk, primarily involved in pathways related to signal transduction, inflammatory response, plasma membrane, protein binding, and cytokine-cytokine receptor interactions. Ranking by P values, the top five proteins associated with increased PAD risk included EDA2R, ADM, NPPB, CD302, and NPC2, while BCAN, UMOD, PLB1, CA6, and KLK3 were the top five proteins inversely associated with PAD risk. Incorporating 45 LASSO-selected proteins or a weighted protein risk score significantly enhanced PAD prediction beyond clinical variables alone, reaching a maximum C-index of 0.835. CONCLUSIONS This study identified plasma proteins associated with PAD risk in individuals with T2D. Adding proteomic data into the clinical model significantly improved PAD prediction.
{"title":"Large-Scale Plasma Proteomics Improves Prediction of Peripheral Artery Disease in Individuals With Type 2 Diabetes: A Prospective Cohort Study","authors":"Hancheng Yu, Jijuan Zhang, Frank Qian, Pang Yao, Kun Xu, Ping Wu, Rui Li, Zixin Qiu, Ruyi Li, Kai Zhu, Lin Li, Tingting Geng, Xuefeng Yu, Danpei Li, Yunfei Liao, An Pan, Gang Liu","doi":"10.2337/dc24-1696","DOIUrl":"https://doi.org/10.2337/dc24-1696","url":null,"abstract":"OBJECTIVE Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction. RESEARCH DESIGN AND METHODS This cohort study included 1,859 individuals with T2D from the UK Biobank. Multivariable-adjusted Cox regression models were used to explore associations between 2,920 plasma proteins and incident PAD. Proteins were further selected as predictors using least absolute shrinkage and selection operator (LASSO) penalty. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, continuous/categorical net reclassification improvement, and integrated discrimination improvement. RESULTS Over a median follow-up of 13.2 years, 157 incident PAD cases occurred. We observed 463 proteins associated with PAD risk, primarily involved in pathways related to signal transduction, inflammatory response, plasma membrane, protein binding, and cytokine-cytokine receptor interactions. Ranking by P values, the top five proteins associated with increased PAD risk included EDA2R, ADM, NPPB, CD302, and NPC2, while BCAN, UMOD, PLB1, CA6, and KLK3 were the top five proteins inversely associated with PAD risk. Incorporating 45 LASSO-selected proteins or a weighted protein risk score significantly enhanced PAD prediction beyond clinical variables alone, reaching a maximum C-index of 0.835. CONCLUSIONS This study identified plasma proteins associated with PAD risk in individuals with T2D. Adding proteomic data into the clinical model significantly improved PAD prediction.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"14 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917029","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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