Klara R. Klein, Ildiko Lingvay, Katherine R. Tuttle, Jennifer E. Flythe
Of the nearly 600,000 people in the U.S. who receive dialysis for chronic kidney failure, >60% have diabetes. People receiving dialysis who have diabetes have worse overall and cardiovascular survival rates than those without diabetes. Diabetes care in the dialysis setting is complicated by kidney failure–related factors that render extrapolation of glycated hemoglobin (HbA1c) targets to the dialysis population unreliable and may change the risk-benefit profiles of glucose-lowering and disease-modifying therapies. No prospective studies have established the optimal glycemic targets in the dialysis population, and few randomized clinical trials of glucose-lowering medications included individuals receiving dialysis. Observational data suggest that both lower and higher HbA1c are associated with mortality in the dialysis population. Existing data suggest the potential for safety and effectiveness of some glucose-lowering medications in the dialysis population, but firm conclusions are hindered by limitations in study design and sample size. While population-specific knowledge gaps about optimal glycemic targets and diabetes medication safety and effectiveness preclude the extension of all general population diabetes guidelines to the dialysis-dependent diabetes population, these uncertainties should not detract from the importance of providing person-centered diabetes care to people receiving dialysis. Diabetes care for individuals with and without dialysis-dependent kidney failure should be holistic, based on individual preferences and prognoses, and tailored to integrate established treatment approaches with proven benefits for glycemic control and cardiovascular risk reduction. Additional research is needed to inform how recent pharmacologic and technological advances can be applied to support such individualized care for people receiving maintenance dialysis.
{"title":"Glycemic Management and Individualized Diabetes Care in Dialysis-Dependent Kidney Failure","authors":"Klara R. Klein, Ildiko Lingvay, Katherine R. Tuttle, Jennifer E. Flythe","doi":"10.2337/dci24-0081","DOIUrl":"https://doi.org/10.2337/dci24-0081","url":null,"abstract":"Of the nearly 600,000 people in the U.S. who receive dialysis for chronic kidney failure, >60% have diabetes. People receiving dialysis who have diabetes have worse overall and cardiovascular survival rates than those without diabetes. Diabetes care in the dialysis setting is complicated by kidney failure–related factors that render extrapolation of glycated hemoglobin (HbA1c) targets to the dialysis population unreliable and may change the risk-benefit profiles of glucose-lowering and disease-modifying therapies. No prospective studies have established the optimal glycemic targets in the dialysis population, and few randomized clinical trials of glucose-lowering medications included individuals receiving dialysis. Observational data suggest that both lower and higher HbA1c are associated with mortality in the dialysis population. Existing data suggest the potential for safety and effectiveness of some glucose-lowering medications in the dialysis population, but firm conclusions are hindered by limitations in study design and sample size. While population-specific knowledge gaps about optimal glycemic targets and diabetes medication safety and effectiveness preclude the extension of all general population diabetes guidelines to the dialysis-dependent diabetes population, these uncertainties should not detract from the importance of providing person-centered diabetes care to people receiving dialysis. Diabetes care for individuals with and without dialysis-dependent kidney failure should be holistic, based on individual preferences and prognoses, and tailored to integrate established treatment approaches with proven benefits for glycemic control and cardiovascular risk reduction. Additional research is needed to inform how recent pharmacologic and technological advances can be applied to support such individualized care for people receiving maintenance dialysis.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"47 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849177","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}
Yanshang Wang, Dan Guo, Yiqi Xia, Mingzheng Hu, Ming Wang, Qianqian Yu, Zhansheng Li, Xiaoyi Zhang, Ruoxi Ding, Miaomiao Zhao, Zhenyu Shi, Dawei Zhu, Ping He
OBJECTIVE To develop a care model for patients with both diabetes and depression and assess the model’s effectiveness. RESEARCH DESIGN AND METHODS In this pragmatic cluster randomized trial, we allocated eight community health centers into two groups: the enhanced usual care group and the intervention group. A comprehensive care plan was developed for the intervention group based on the integrated care model. We recruited individuals aged ≥18 years with type 2 diabetes and depression (Patient Health Questionnaire-9 score ≥10). The primary outcome was the between-group difference in the percentage of patients who had at least a 50% reduction in depressive symptoms and a reduction of at least 0.5 percentage points in HbA1c. The outcome analysis was conducted within the intention-to-treat population; missing data were multiply imputed. RESULTS We enrolled 630 participants, with 275 in the intervention group and 355 in the control group. A significantly greater percentage of patients in the intervention group met the primary outcome at 12 months (for depressive symptoms: risk difference [RD] 31.03% [62.06% vs. 31.02%, respectively; 95% CI 21.85–40.21]; for HbA1c: RD 19.16% [32.41% vs. 13.25%, respectively; 95% CI 11.35–26.97]). The patients in the intervention group showed significant enhancements in mental quality of life (mean difference [MD] 6.74 [46.57 vs. 39.83, respectively; 95% CI 3.75–9.74]), diabetes self-care activities (MD 0.69 [3.46 vs. 2.78, respectively; 95% CI 0.52–0.86]), medication adherence (MD 0.72 [6.49 vs. 5.78, respectively; 95% CI 0.37–1.07]), and experience of care (MD 0.89 [3.84 vs. 2.95, respectively; 95% CI 0.65–1.12]) at 12 months. Rural participants benefited more from the intervention. CONCLUSIONS The implementation strategy can serve as a valuable blueprint for the identification and treatment of patients with physical and mental multimorbidity in primary health care settings.
目的建立糖尿病合并抑郁症患者的护理模式，并评价该模式的有效性。研究设计与方法在本实用主义聚类随机试验中，我们将8个社区卫生中心分为两组：强化常规护理组和干预组。根据综合护理模式为干预组制定综合护理计划。我们招募年龄≥18岁的2型糖尿病和抑郁症患者（患者健康问卷-9得分≥10）。主要结局是抑郁症状减轻至少50%，HbA1c降低至少0.5个百分点的患者百分比的组间差异。结果分析在意向治疗人群中进行；对缺失数据进行多重输入。结果：我们招募了630名参与者，其中干预组275名，对照组355名。干预组患者在12个月时达到主要结局的比例显著更高(抑郁症状：风险差[RD]分别为31.03% [62.06%:31.02%；95% ci 21.85-40.21]；HbA1c: RD为19.16% [32.41% vs. 13.25%]；95% ci 11.35-26.97])。干预组患者心理生活质量显著提高(平均差值[MD] 6.74 [46.57: 39.83]；95% CI 3.75-9.74])，糖尿病自我护理活动(MD 0.69[分别为3.46 vs. 2.78；95% CI 0.52-0.86])、药物依从性(MD 0.72[分别为6.49 vs. 5.78；95% CI 0.37-1.07])和护理经验(MD 0.89[分别为3.84比2.95；95% CI 0.65-1.12])。农村参与者从干预中受益更多。结论该实施策略可作为初级卫生保健机构识别和治疗身心多病患者的有价值蓝图。
{"title":"Effect of Community-Based Integrated Care for Patients With Diabetes and Depression (CIC-PDD) in China: A Pragmatic Cluster-Randomized Trial","authors":"Yanshang Wang, Dan Guo, Yiqi Xia, Mingzheng Hu, Ming Wang, Qianqian Yu, Zhansheng Li, Xiaoyi Zhang, Ruoxi Ding, Miaomiao Zhao, Zhenyu Shi, Dawei Zhu, Ping He","doi":"10.2337/dc24-1593","DOIUrl":"https://doi.org/10.2337/dc24-1593","url":null,"abstract":"OBJECTIVE To develop a care model for patients with both diabetes and depression and assess the model’s effectiveness. RESEARCH DESIGN AND METHODS In this pragmatic cluster randomized trial, we allocated eight community health centers into two groups: the enhanced usual care group and the intervention group. A comprehensive care plan was developed for the intervention group based on the integrated care model. We recruited individuals aged ≥18 years with type 2 diabetes and depression (Patient Health Questionnaire-9 score ≥10). The primary outcome was the between-group difference in the percentage of patients who had at least a 50% reduction in depressive symptoms and a reduction of at least 0.5 percentage points in HbA1c. The outcome analysis was conducted within the intention-to-treat population; missing data were multiply imputed. RESULTS We enrolled 630 participants, with 275 in the intervention group and 355 in the control group. A significantly greater percentage of patients in the intervention group met the primary outcome at 12 months (for depressive symptoms: risk difference [RD] 31.03% [62.06% vs. 31.02%, respectively; 95% CI 21.85–40.21]; for HbA1c: RD 19.16% [32.41% vs. 13.25%, respectively; 95% CI 11.35–26.97]). The patients in the intervention group showed significant enhancements in mental quality of life (mean difference [MD] 6.74 [46.57 vs. 39.83, respectively; 95% CI 3.75–9.74]), diabetes self-care activities (MD 0.69 [3.46 vs. 2.78, respectively; 95% CI 0.52–0.86]), medication adherence (MD 0.72 [6.49 vs. 5.78, respectively; 95% CI 0.37–1.07]), and experience of care (MD 0.89 [3.84 vs. 2.95, respectively; 95% CI 0.65–1.12]) at 12 months. Rural participants benefited more from the intervention. CONCLUSIONS The implementation strategy can serve as a valuable blueprint for the identification and treatment of patients with physical and mental multimorbidity in primary health care settings.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"76 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831963","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 We aim to compare the risk of nephrolithiasis among type 2 diabetes patients who initiated sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl-peptidase-4 inhibitors (DPP4is), individually within stone never- and ever-formers. RESEARCH DESIGN AND METHODS Using the 2010–2021 Korea National Health Insurance Service database, we conducted a population-based cohort study, comparing initiators of SGLT2is versus DPP4is. The primary outcome was incident nephrolithiasis. Osteoarthritis encounters served as a negative control outcome. After 1:1 propensity score (PS) matching in stone never- and ever-formers, pooled and individual hazard ratios (HRs), incidence rate difference (IRD), and 95% CIs were reported. Subgroup analyses by sex, age, thiazide co-use, and baseline cardiovascular risk were done. RESULTS The 17,006 PS-matched pairs of SGLT2i and DPP4i initiators were pooled from stone never- (105,378 pairs) and ever-formers (11,628 pairs). Over a mean of 654 days, the risk of nephrolithiasis was lower in SGLT2i initiators than in DPP4i: 0.65 vs. 1.12 events per 100 person-years, HR 0.54 (95% CI, 0.50–0.57), IRD −0.46 (95% CI,−0.21 to −0.52). Among never-formers, the HR was 0.43 (95% CI, 0.39–0.48) and IRD was −0.32 (95% CI,−0.27 to −0.36). Among ever-formers, the HR was 0.64 (95% CI, 0.59–0.69) and IRD was −2.26 (95% CI,−1.77 to −2.76). Near-null associations were found for osteoarthritis encounters. Results were consistent across subgroups. CONCLUSIONS We found a lower risk of nephrolithiasis associated with SGLT2is versus DPP4is in stone never- and ever-formers. Despite a greater relative risk reduction in the former, the absolute risk reduction was greater in the latter.
{"title":"Risk of Nephrolithiasis Associated With SGLT2 Inhibitors Versus DPP4 Inhibitors Among Patients With Type 2 Diabetes: A Target Trial Emulation Study","authors":"Anna Shin, Ju-Young Shin, Eun Ha Kang","doi":"10.2337/dc24-1652","DOIUrl":"https://doi.org/10.2337/dc24-1652","url":null,"abstract":"OBJECTIVE We aim to compare the risk of nephrolithiasis among type 2 diabetes patients who initiated sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl-peptidase-4 inhibitors (DPP4is), individually within stone never- and ever-formers. RESEARCH DESIGN AND METHODS Using the 2010–2021 Korea National Health Insurance Service database, we conducted a population-based cohort study, comparing initiators of SGLT2is versus DPP4is. The primary outcome was incident nephrolithiasis. Osteoarthritis encounters served as a negative control outcome. After 1:1 propensity score (PS) matching in stone never- and ever-formers, pooled and individual hazard ratios (HRs), incidence rate difference (IRD), and 95% CIs were reported. Subgroup analyses by sex, age, thiazide co-use, and baseline cardiovascular risk were done. RESULTS The 17,006 PS-matched pairs of SGLT2i and DPP4i initiators were pooled from stone never- (105,378 pairs) and ever-formers (11,628 pairs). Over a mean of 654 days, the risk of nephrolithiasis was lower in SGLT2i initiators than in DPP4i: 0.65 vs. 1.12 events per 100 person-years, HR 0.54 (95% CI, 0.50–0.57), IRD −0.46 (95% CI,−0.21 to −0.52). Among never-formers, the HR was 0.43 (95% CI, 0.39–0.48) and IRD was −0.32 (95% CI,−0.27 to −0.36). Among ever-formers, the HR was 0.64 (95% CI, 0.59–0.69) and IRD was −2.26 (95% CI,−1.77 to −2.76). Near-null associations were found for osteoarthritis encounters. Results were consistent across subgroups. CONCLUSIONS We found a lower risk of nephrolithiasis associated with SGLT2is versus DPP4is in stone never- and ever-formers. Despite a greater relative risk reduction in the former, the absolute risk reduction was greater in the latter.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"92 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815500","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}
Katherine E. Griffin, Kathryn Snyder, Amir H. Javid, Amber Hackstadt, Robert Greevy, Carlos G. Grijalva, Christianne L. Roumie
OBJECTIVE To compare the risk of composite peripheral artery disease (PAD) surgical outcome, including peripheral revascularization and amputation procedures, between new users of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP-4is). RESEARCH DESIGN AND METHODS This retrospective cohort study of U.S. veterans age ≥18 years with diabetes who received care from the Veterans Health Administration was performed from 1 October 2000 to 31 December 2021. Data were linked to Medicare, Medicaid, and the National Death Index. New use of SGLT2i or DPP-4i medications as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination was evaluated for an association with PAD surgical procedure for peripheral revascularization and amputation. A Cox proportional hazards model for time-to-PAD event analysis compared the risk of a PAD event between SGLT2is and DPP-4is in a propensity score–weighted cohort with a competing risk of death and allowance for events to occur up to 90 days or 360 days after stopping SGLT2is. RESULTS The weighted cohort included 76,072 SGLT2i vs. 75,833 DPP-4i use episodes. The median age was 69 years, HbA1c was 8.4% (interquartile range [IQR] 7.5–9.4%), and the median diabetes duration was 10.1 (IQR 6.6–14.6) years. There were 874 and 780 PAD events among SGLT2i and DPP-4i users, respectively, for an event rate of 11.2 (95% CI 10.5–11.9) and 10.0 (9.4–10.6) per 1,000 person-years (adjusted hazard ratio [aHR] 1.18 [95% CI 1.08–1.29]). When PAD events were allowed for 360 days after SGLT2i use ended, the aHR was 1.16 (95% CI 1.06–1.26). CONCLUSIONS SGLT2i as an add-on diabetes therapy was associated with an increased cause-specific hazard of PAD surgeries compared with DPP-4i.
目的比较新使用钠-葡萄糖共转运蛋白2抑制剂（SGLT2is）和二肽基肽酶4抑制剂（DPP-4is）的患者发生复合外周动脉疾病（PAD）手术结果的风险，包括外周血运重建和截肢手术。研究设计和方法本回顾性队列研究纳入了2000年10月1日至2021年12月31日期间接受退伍军人健康管理局护理的年龄≥18岁的糖尿病美国退伍军人。数据与医疗保险、医疗补助和国家死亡指数相关联。新使用的SGLT2i或DPP-4i药物作为二甲双胍、磺脲类药物或胰岛素单独或联合治疗的附加治疗与PAD手术外周血运重建和截肢的相关性进行了评估。用于PAD事件时间分析的Cox比例风险模型比较了倾向评分加权队列中SGLT2is和dpp -4患者之间PAD事件的风险，该队列具有竞争死亡风险，并允许在停止SGLT2is后90天或360天内发生事件。结果：加权队列包括76,072例SGLT2i和75,833例DPP-4i使用事件。中位年龄为69岁，HbA1c为8.4%（四分位数间距[IQR] 7.5-9.4%），中位糖尿病病程为10.1年（IQR为6.6-14.6）。SGLT2i和DPP-4i使用者中分别有874和780例PAD事件，事件发生率为每1000人年11.2例（95% CI 10.5-11.9）和10.0例（9.4-10.6）（校正风险比[aHR] 1.18 [95% CI 1.08-1.29]）。当停止使用SGLT2i后360天允许PAD事件发生时，aHR为1.16 （95% CI 1.06-1.26）。结论：与DPP-4i相比，SGLT2i作为附加糖尿病治疗与PAD手术的病因特异性风险增加相关。
{"title":"Use of SGLT2i Versus DPP-4i as an Add-On Therapy and the Risk of PAD-Related Surgical Events (Amputation, Stent Placement, or Vascular Surgery): A Cohort Study in Veterans With Diabetes","authors":"Katherine E. Griffin, Kathryn Snyder, Amir H. Javid, Amber Hackstadt, Robert Greevy, Carlos G. Grijalva, Christianne L. Roumie","doi":"10.2337/dc24-1546","DOIUrl":"https://doi.org/10.2337/dc24-1546","url":null,"abstract":"OBJECTIVE To compare the risk of composite peripheral artery disease (PAD) surgical outcome, including peripheral revascularization and amputation procedures, between new users of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP-4is). RESEARCH DESIGN AND METHODS This retrospective cohort study of U.S. veterans age ≥18 years with diabetes who received care from the Veterans Health Administration was performed from 1 October 2000 to 31 December 2021. Data were linked to Medicare, Medicaid, and the National Death Index. New use of SGLT2i or DPP-4i medications as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination was evaluated for an association with PAD surgical procedure for peripheral revascularization and amputation. A Cox proportional hazards model for time-to-PAD event analysis compared the risk of a PAD event between SGLT2is and DPP-4is in a propensity score–weighted cohort with a competing risk of death and allowance for events to occur up to 90 days or 360 days after stopping SGLT2is. RESULTS The weighted cohort included 76,072 SGLT2i vs. 75,833 DPP-4i use episodes. The median age was 69 years, HbA1c was 8.4% (interquartile range [IQR] 7.5–9.4%), and the median diabetes duration was 10.1 (IQR 6.6–14.6) years. There were 874 and 780 PAD events among SGLT2i and DPP-4i users, respectively, for an event rate of 11.2 (95% CI 10.5–11.9) and 10.0 (9.4–10.6) per 1,000 person-years (adjusted hazard ratio [aHR] 1.18 [95% CI 1.08–1.29]). When PAD events were allowed for 360 days after SGLT2i use ended, the aHR was 1.16 (95% CI 1.06–1.26). CONCLUSIONS SGLT2i as an add-on diabetes therapy was associated with an increased cause-specific hazard of PAD surgeries compared with DPP-4i.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"10 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797019","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}
Carolyn McGrail, Joshua Chiou, Ruth Egamal, Amber M. Luckett, Richard A. Oram, Paola Benaglio, Kyle J. Gaulton
OBJECTIVE More than 10% of patients with type 1 diabetes (T1D) do not have high-risk HLA-DR3 or -DR4 haplotypes with distinct clinical features, such as later onset and reduced insulin dependence. We aimed to identify genetic drivers of T1D in the absence of DR3/DR4 and improve prediction of T1D risk in these individuals. RESEARCH DESIGN AND METHODS We performed T1D association and fine-mapping analyses in 12,316 non-DR3/DR4 samples. Next, we performed heterogeneity tests to examine differences in T1D risk variants in individuals without versus those with DR3/DR4 haplotypes. We further assessed genome-wide differences in gene regulatory element and biological pathway enrichments between the non-DR3/DR4 and DR3/DR4 cohorts. Finally, we developed a genetic risk score (GRS) to predict T1D in individuals without DR3/DR4 and compared with an existing T1D GRS. RESULTS A total of 18 T1D risk variants in non-DR3/DR4 samples were identified. Risk variants at the MHC and multiple other loci genome wide had heterogeneity in effects on T1D dependent on DR3/DR4 status, and non-DR3/DR4 T1D had evidence for a greater polygenic burden. T1D-assocated variants in non-DR3/DR4 were more enriched for regulatory elements and pathways involved in antigen presentation, innate immunity, and β-cells and depleted in T cells compared with DR3/DR4. A non-DR3/DR4 GRS outperformed an existing risk score GRS2 in discriminating non-DR3/DR4 T1D from no diabetes (area under the curve 0.867; P = 7.48 × 10−32) and type 2 diabetes (0.907; P = 4.94 × 10−44). CONCLUSIONS In total, we identified heterogeneity in T1D genetic risk dependent on high-risk HLA-DR3/DR4 haplotype, which uncovers disease mechanisms and enables more accurate prediction of T1D across the HLA background.
{"title":"Genetic Discovery and Risk Prediction for Type 1 Diabetes in Individuals Without High-Risk HLA-DR3/DR4 Haplotypes","authors":"Carolyn McGrail, Joshua Chiou, Ruth Egamal, Amber M. Luckett, Richard A. Oram, Paola Benaglio, Kyle J. Gaulton","doi":"10.2337/dc24-1251","DOIUrl":"https://doi.org/10.2337/dc24-1251","url":null,"abstract":"OBJECTIVE More than 10% of patients with type 1 diabetes (T1D) do not have high-risk HLA-DR3 or -DR4 haplotypes with distinct clinical features, such as later onset and reduced insulin dependence. We aimed to identify genetic drivers of T1D in the absence of DR3/DR4 and improve prediction of T1D risk in these individuals. RESEARCH DESIGN AND METHODS We performed T1D association and fine-mapping analyses in 12,316 non-DR3/DR4 samples. Next, we performed heterogeneity tests to examine differences in T1D risk variants in individuals without versus those with DR3/DR4 haplotypes. We further assessed genome-wide differences in gene regulatory element and biological pathway enrichments between the non-DR3/DR4 and DR3/DR4 cohorts. Finally, we developed a genetic risk score (GRS) to predict T1D in individuals without DR3/DR4 and compared with an existing T1D GRS. RESULTS A total of 18 T1D risk variants in non-DR3/DR4 samples were identified. Risk variants at the MHC and multiple other loci genome wide had heterogeneity in effects on T1D dependent on DR3/DR4 status, and non-DR3/DR4 T1D had evidence for a greater polygenic burden. T1D-assocated variants in non-DR3/DR4 were more enriched for regulatory elements and pathways involved in antigen presentation, innate immunity, and β-cells and depleted in T cells compared with DR3/DR4. A non-DR3/DR4 GRS outperformed an existing risk score GRS2 in discriminating non-DR3/DR4 T1D from no diabetes (area under the curve 0.867; P = 7.48 × 10−32) and type 2 diabetes (0.907; P = 4.94 × 10−44). CONCLUSIONS In total, we identified heterogeneity in T1D genetic risk dependent on high-risk HLA-DR3/DR4 haplotype, which uncovers disease mechanisms and enables more accurate prediction of T1D across the HLA background.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"14 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763244","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}
Joshua J. Neumiller, Mandeep Bajaj, Raveendhara R. Bannuru, Rozalina G. McCoy, Elizabeth J. Pekas, Alissa R. Segal, Nuha A. ElSayed
The use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA (GIP/GLP-1 RA) classes has increased substantially over the past several years for treating type 2 diabetes and obesity. Increased demand for these pharmacotherapies has resulted in temporary product shortages for both GLP-1 RA and dual GIP/GLP-1 RA medications. These shortages, in part, have led to entities producing and marketing compounded formulations that bypass regulatory measures, raising safety, quality, and efficacy concerns. Even as shortages resolve, compounded GLP-1 RA and GIP/GLP-1 RA products continue to be heavily marketed to people with diabetes and obesity. The purpose of this statement by the American Diabetes Association is to guide health care professionals and people with diabetes and/or obesity in these circumstances of medication unavailability to promote optimal care and medication use safety.
胰高血糖素样肽1受体激动剂（GLP-1 RA）和双葡萄糖依赖性胰岛素多肽（GIP）和GLP-1 RA （GIP/GLP-1 RA）类别在过去几年中用于治疗2型糖尿病和肥胖症的使用大幅增加。对这些药物治疗的需求增加导致GLP-1 RA和双GIP/GLP-1 RA药物的暂时产品短缺。这些短缺在一定程度上导致实体生产和销售绕过监管措施的复方制剂，引起了对安全、质量和功效的担忧。即使短缺得到解决，复合GLP-1 RA和GIP/GLP-1 RA产品继续大量销售给糖尿病和肥胖症患者。美国糖尿病协会的这一声明的目的是指导医疗保健专业人员和糖尿病和/或肥胖患者在这些药物不可用的情况下促进最佳护理和药物使用安全。
{"title":"Compounded GLP 1 and Dual GIP/GLP 1 Receptor Agonists: A Statement from the American Diabetes Association","authors":"Joshua J. Neumiller, Mandeep Bajaj, Raveendhara R. Bannuru, Rozalina G. McCoy, Elizabeth J. Pekas, Alissa R. Segal, Nuha A. ElSayed","doi":"10.2337/dci24-0091","DOIUrl":"https://doi.org/10.2337/dci24-0091","url":null,"abstract":"The use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA (GIP/GLP-1 RA) classes has increased substantially over the past several years for treating type 2 diabetes and obesity. Increased demand for these pharmacotherapies has resulted in temporary product shortages for both GLP-1 RA and dual GIP/GLP-1 RA medications. These shortages, in part, have led to entities producing and marketing compounded formulations that bypass regulatory measures, raising safety, quality, and efficacy concerns. Even as shortages resolve, compounded GLP-1 RA and GIP/GLP-1 RA products continue to be heavily marketed to people with diabetes and obesity. The purpose of this statement by the American Diabetes Association is to guide health care professionals and people with diabetes and/or obesity in these circumstances of medication unavailability to promote optimal care and medication use safety.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"45 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760317","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}
Neha Garg, Kamryn Lewis, Perrin C. White, Soumya Adhikari
OBJECTIVE The adoption of continuous glucose monitors (CGMs) in inpatient settings in the pediatric population has been slow because of a scarcity of data on their reliability in hospitalized children. RESEARCH DESIGN AND METHODS We retrospectively reviewed the accuracy of the Dexcom G6 CGM system in pediatric patients with diabetes admitted to our academic children’s hospital from March 2018 to September 2023. We cross-referenced the Dexcom Clarity database against an internal database of inpatient admissions to identify all children with CGM data admitted to the hospital. We recorded sensor glucose readings from Clarity and values for point-of-care (POC) glucose, blood urea nitrogen (BUN), and pH from the electronic medical record. CGM accuracy and clinical reliability were measured by mean absolute relative difference (MARD) and Clarke error grid (CEG) analyses. RESULTS There were 3,200 admissions of children with diabetes in this period, of which 277 (from 202 patients age 2–18 years) had associated CGM data. Paired CGM and POC measurements (n = 2,904) were compared, resulting in an MARD of 15.9%, with 96.6% of the values in zones A and B of the CEG analysis. Approximately 62% of paired values fell within a 15% or 15 mg/dL difference, whichever was larger (15%/15 mg/dL range), 74% within 20%/20, and 88% within 30%/30. Serum pH, sodium, and BUN had no impact on CGM values or absolute relative difference in linear regression analysis. CONCLUSIONS CGMs demonstrated acceptable accuracy in hospitalized children with diabetes. CGM data should be integrated into hospital electronic records to optimize management.
{"title":"Continuous Glucose Monitor Accuracy for Diabetes Management in Hospitalized Children","authors":"Neha Garg, Kamryn Lewis, Perrin C. White, Soumya Adhikari","doi":"10.2337/dc24-1562","DOIUrl":"https://doi.org/10.2337/dc24-1562","url":null,"abstract":"OBJECTIVE The adoption of continuous glucose monitors (CGMs) in inpatient settings in the pediatric population has been slow because of a scarcity of data on their reliability in hospitalized children. RESEARCH DESIGN AND METHODS We retrospectively reviewed the accuracy of the Dexcom G6 CGM system in pediatric patients with diabetes admitted to our academic children’s hospital from March 2018 to September 2023. We cross-referenced the Dexcom Clarity database against an internal database of inpatient admissions to identify all children with CGM data admitted to the hospital. We recorded sensor glucose readings from Clarity and values for point-of-care (POC) glucose, blood urea nitrogen (BUN), and pH from the electronic medical record. CGM accuracy and clinical reliability were measured by mean absolute relative difference (MARD) and Clarke error grid (CEG) analyses. RESULTS There were 3,200 admissions of children with diabetes in this period, of which 277 (from 202 patients age 2–18 years) had associated CGM data. Paired CGM and POC measurements (n = 2,904) were compared, resulting in an MARD of 15.9%, with 96.6% of the values in zones A and B of the CEG analysis. Approximately 62% of paired values fell within a 15% or 15 mg/dL difference, whichever was larger (15%/15 mg/dL range), 74% within 20%/20, and 88% within 30%/30. Serum pH, sodium, and BUN had no impact on CGM values or absolute relative difference in linear regression analysis. CONCLUSIONS CGMs demonstrated acceptable accuracy in hospitalized children with diabetes. CGM data should be integrated into hospital electronic records to optimize management.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"204 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760506","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}
Gidon J. Bönhof, Alexander Strom, Tobias Jung, Kálmán B. Bódis, Julia Szendroedi, Robert Wagner, Tilman Grune, Michael Roden, Dan Ziegler
OBJECTIVE Endogenous carbonyl stress leads to the formation of advanced glycation end products (AGEs). AGEs represent a potential target to prevent or treat diabetic sensorimotor polyneuropathy (DSPN). The current study aimed to characterize cutaneous carbonyl stress, oxidative stress, immune cells, and endothelial cell damage in early type 2 diabetes compared with normal glucose tolerance (NGT) using novel cutaneous biomarkers. RESEARCH DESIGN AND METHODS Included were 160 individuals recently (≤12 months) diagnosed with type 2 diabetes and 144 with NGT from the German Diabetes Study baseline cohort. Nerve function was assessed using electrophysiological, quantitative sensory, and clinical testing. Skin biopsies were obtained to analyze intraepidermal nerve fiber density, AGEs autofluorescence, argpyrimidine area, and endothelial cell area. In addition, skin autofluorescence was measured noninvasively using the AGE reader. A subgroup with type 2 diabetes (n = 80) was reassessed 5 years later. RESULTS After adjustment for sex, age, HbA1c, LDL cholesterol, and BMI, argpyrimidine area (17.5 ± 18.8 vs. 11.7 ± 12.7%) was higher in recent-onset type 2 diabetes than in NGT (P < 0.05). AGEs autofluorescence was inversely correlated with nerve conduction (e.g., peroneal motor nerve conduction velocity: r = −0.346) and positively with AGE reader measurements in type 2 diabetes (r = 0.358, all P < 0.05), but not in NGT. Higher baseline AGEs autofluorescence and lower endothelial cell area predicted the deterioration of clinical and neurophysiological measures after 5 years. CONCLUSIONS Cutaneous AGEs markers were associated with neurophysiological deficits in recent-onset type 2 diabetes and predicted their progression after 5 years, substantiating the role of carbonyl stress in the development of early DSPN.
{"title":"Cutaneous Carbonyl Stress Is Associated With Nerve Dysfunction in Recent-Onset Type 2 Diabetes","authors":"Gidon J. Bönhof, Alexander Strom, Tobias Jung, Kálmán B. Bódis, Julia Szendroedi, Robert Wagner, Tilman Grune, Michael Roden, Dan Ziegler","doi":"10.2337/dc24-1799","DOIUrl":"https://doi.org/10.2337/dc24-1799","url":null,"abstract":"OBJECTIVE Endogenous carbonyl stress leads to the formation of advanced glycation end products (AGEs). AGEs represent a potential target to prevent or treat diabetic sensorimotor polyneuropathy (DSPN). The current study aimed to characterize cutaneous carbonyl stress, oxidative stress, immune cells, and endothelial cell damage in early type 2 diabetes compared with normal glucose tolerance (NGT) using novel cutaneous biomarkers. RESEARCH DESIGN AND METHODS Included were 160 individuals recently (≤12 months) diagnosed with type 2 diabetes and 144 with NGT from the German Diabetes Study baseline cohort. Nerve function was assessed using electrophysiological, quantitative sensory, and clinical testing. Skin biopsies were obtained to analyze intraepidermal nerve fiber density, AGEs autofluorescence, argpyrimidine area, and endothelial cell area. In addition, skin autofluorescence was measured noninvasively using the AGE reader. A subgroup with type 2 diabetes (n = 80) was reassessed 5 years later. RESULTS After adjustment for sex, age, HbA1c, LDL cholesterol, and BMI, argpyrimidine area (17.5 ± 18.8 vs. 11.7 ± 12.7%) was higher in recent-onset type 2 diabetes than in NGT (P &lt; 0.05). AGEs autofluorescence was inversely correlated with nerve conduction (e.g., peroneal motor nerve conduction velocity: r = −0.346) and positively with AGE reader measurements in type 2 diabetes (r = 0.358, all P &lt; 0.05), but not in NGT. Higher baseline AGEs autofluorescence and lower endothelial cell area predicted the deterioration of clinical and neurophysiological measures after 5 years. CONCLUSIONS Cutaneous AGEs markers were associated with neurophysiological deficits in recent-onset type 2 diabetes and predicted their progression after 5 years, substantiating the role of carbonyl stress in the development of early DSPN.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"33 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712532","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}
Ernesto Maddaloni, Maggie Nguyen, Svati H. Shah, Rury R. Holman
OBJECTIVE To evaluate the association of four bone metabolism biomarkers (osteoprotegerin, osteopontin, sclerostin, and osteocalcin) with cardiovascular events in people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was a randomized clinical trial evaluating the cardiovascular (CV) safety and efficacy of once-weekly exenatide for patients with T2D. Candidate biomarker data were selected from proteomic profiling performed at baseline and 12 months after randomization samples by SomaScan assay in 5,473 trial participants. The primary composite outcome was the first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (major cardiovascular events [MACE]). Cox proportional hazards models controlling for confounders were used for time-to-event analyses to calculate hazard ratios (HRs) with 95% CI for a 1 SD increase in the biomarker concentrations. RESULTS The primary outcome occurred in 813 participants (14.9%). Higher levels of osteoprotegerin (HR 1.11; 95% CI 1.03–1.20; P = 0.0047) and osteopontin (HR 1.10; 95% CI 1.02–1.18; P = 0.0095) were associated with an increased risk of MACE. The addition of osteoprotegerin and osteopontin to a clinical predictive model containing traditional CV risk factors provided minimal incremental value for MACE prediction (C-index 0.629 vs. 0.638; likelihood ratio test P < 0.001). Osteocalcin and sclerostin were not associated with MACE. Osteocalcin had a nonlinear association with all-cause death and with CV death. CONCLUSIONS Higher levels of osteoprotegerin and osteopontin are associated with an increased risk of CV events in people with T2D, supporting the hypothesis that pathways involved in bone metabolism play a role in CV disease.
{"title":"Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL","authors":"Ernesto Maddaloni, Maggie Nguyen, Svati H. Shah, Rury R. Holman","doi":"10.2337/dc24-1455","DOIUrl":"https://doi.org/10.2337/dc24-1455","url":null,"abstract":"OBJECTIVE To evaluate the association of four bone metabolism biomarkers (osteoprotegerin, osteopontin, sclerostin, and osteocalcin) with cardiovascular events in people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was a randomized clinical trial evaluating the cardiovascular (CV) safety and efficacy of once-weekly exenatide for patients with T2D. Candidate biomarker data were selected from proteomic profiling performed at baseline and 12 months after randomization samples by SomaScan assay in 5,473 trial participants. The primary composite outcome was the first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (major cardiovascular events [MACE]). Cox proportional hazards models controlling for confounders were used for time-to-event analyses to calculate hazard ratios (HRs) with 95% CI for a 1 SD increase in the biomarker concentrations. RESULTS The primary outcome occurred in 813 participants (14.9%). Higher levels of osteoprotegerin (HR 1.11; 95% CI 1.03–1.20; P = 0.0047) and osteopontin (HR 1.10; 95% CI 1.02–1.18; P = 0.0095) were associated with an increased risk of MACE. The addition of osteoprotegerin and osteopontin to a clinical predictive model containing traditional CV risk factors provided minimal incremental value for MACE prediction (C-index 0.629 vs. 0.638; likelihood ratio test P &lt; 0.001). Osteocalcin and sclerostin were not associated with MACE. Osteocalcin had a nonlinear association with all-cause death and with CV death. CONCLUSIONS Higher levels of osteoprotegerin and osteopontin are associated with an increased risk of CV events in people with T2D, supporting the hypothesis that pathways involved in bone metabolism play a role in CV disease.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"66 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690535","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}
Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A. Staggers, Meredith McCormack, Dennis T. Villareal, Ivan O. Rosas, Nicola A. Hanania, Tianshi David Wu
OBJECTIVE Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident lung disease was determined by a study examiner. The relationship of HOMA-IR to these outcomes was estimated in models adjusted for demographics, BMI, and lifetime smoking. RESULTS A total of 875 participants with longitudinal IR data and outcomes were identified. Their mean age was 51.5 years, and BMI was 26.7 kg/m2. HOMA-IR was temporally unstable, with a within-person SD approximately two-thirds of the between-person SD. In adjusted models, a 1 SD increase in log(HOMA-IR) z score was associated with higher odds of qualitative emphysema (odds ratio [OR] 1.33; 95% CI 1.04–1.70), ILAs (OR 1.35; 95% CI 1.05–1.74), and modest increases in airway wall thickness and wall area percentage. These radiographic findings were corroborated by a positive association of HOMA-IR with incident lung disease. CONCLUSIONS IR is associated with radiographic lung abnormalities and incident lung disease. Deeper phenotyping is necessary to define mechanisms of IR-associated lung injury.
目的 胰岛素抵抗（IR）可能是肺部疾病的风险因素，但客观证据有限。我们试图在弗雷明汉后代研究（Framingham Offspring Study）中确定纵向胰岛素抵抗与放射成像结果和检查者发现的肺部疾病之间的关系。研究设计与方法 没有基线肺病的参与者在平均 13.6 年的时间里重复测量空腹胰岛素和葡萄糖水平，并从中计算出时间加权平均 HOMA-IR 值。然后，每位受试者接受心脏门控全肺计算机断层扫描，分析是否存在肺气肿、肺间质异常（ILAs）和气道定量特征。肺部疾病由研究人员确定。在根据人口统计学、体重指数和终生吸烟情况进行调整后的模型中估算了 HOMA-IR 与这些结果之间的关系。结果 共确定了 875 名具有纵向 IR 数据和结果的参与者。他们的平均年龄为 51.5 岁，体重指数为 26.7 kg/m2。HOMA-IR 具有时间不稳定性，人内 SD 值约为人际 SD 值的三分之二。在调整模型中，log(HOMA-IR) z 评分每增加 1 SD，肺气肿定性几率（几率比 [OR] 1.33；95% CI 1.04-1.70）、ILAs（OR 1.35；95% CI 1.05-1.74）以及气道壁厚度和气道壁面积百分比就会增加。HOMA-IR与肺部疾病的发生呈正相关，这也证实了这些影像学发现。结论 IR 与肺部影像学异常和肺部疾病有关。有必要进行更深入的表型分析，以确定 IR 相关肺损伤的机制。
{"title":"Association of Insulin Resistance With Radiographic Lung Abnormalities and Incident Lung Disease: The Framingham Offspring Study","authors":"Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A. Staggers, Meredith McCormack, Dennis T. Villareal, Ivan O. Rosas, Nicola A. Hanania, Tianshi David Wu","doi":"10.2337/dc24-1754","DOIUrl":"https://doi.org/10.2337/dc24-1754","url":null,"abstract":"OBJECTIVE Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident lung disease was determined by a study examiner. The relationship of HOMA-IR to these outcomes was estimated in models adjusted for demographics, BMI, and lifetime smoking. RESULTS A total of 875 participants with longitudinal IR data and outcomes were identified. Their mean age was 51.5 years, and BMI was 26.7 kg/m2. HOMA-IR was temporally unstable, with a within-person SD approximately two-thirds of the between-person SD. In adjusted models, a 1 SD increase in log(HOMA-IR) z score was associated with higher odds of qualitative emphysema (odds ratio [OR] 1.33; 95% CI 1.04–1.70), ILAs (OR 1.35; 95% CI 1.05–1.74), and modest increases in airway wall thickness and wall area percentage. These radiographic findings were corroborated by a positive association of HOMA-IR with incident lung disease. CONCLUSIONS IR is associated with radiographic lung abnormalities and incident lung disease. Deeper phenotyping is necessary to define mechanisms of IR-associated lung injury.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"198 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684142","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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