Diabetes Care最新文献

{"title":"In This Issue of <i>Diabetes Care</i>","authors":"Max Bingham","doi":"10.2337/dc23-ti10","DOIUrl":"https://doi.org/10.2337/dc23-ti10","url":null,"abstract":"","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136307085","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}

{"title":"Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Santé Cohort.","authors":"Charlotte Debras, Mélanie Deschasaux-Tanguy, Eloi Chazelas, Laury Sellem, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Pilar Galan, Serge Hercberg, Inge Huybrechts, Emmanuel Cosson, Sopio Tatulashvili, Bernard Srour, Mathilde Touvier","doi":"10.2337/dc23-0206","DOIUrl":"10.2337/dc23-0206","url":null,"abstract":"<p><strong>Objective: </strong>To study the relationships between artificial sweeteners, accounting for all dietary sources (total and by type of artificial sweetener) and risk of type 2 diabetes (T2D), in a large-scale prospective cohort.</p><p><strong>Research design and methods: </strong>The analyses included 105,588 participants from the web-based NutriNet-Santé study (France, 2009-2022; mean age 42.5 ± 14.6 years, 79.2% women). Repeated 24-h dietary records, including brands and commercial names of industrial products, merged with qualitative and quantitative food additive composition data, enabled artificial sweetener intakes to be accurately assessed from all dietary sources. Associations between artificial sweeteners (total, aspartame, acesulfame potassium [K], and sucralose) and T2D were investigated using Cox proportional hazard models adjusted for potential confounders, including weight variation during follow-up.</p><p><strong>Results: </strong>During a median follow-up of 9.1 years (946,650 person-years, 972 incident T2D), compared with nonconsumers, higher consumers of artificial sweeteners (i.e., above the sex-specific medians of 16.4 mg/day in men and 18.5 mg/day in women) had higher risks of developing T2D (hazard ratio [HR] 1.69; 95% CI 1.45-1.97; P-trend <0.001). Positive associations were also observed for individual artificial sweeteners: aspartame (HR 1.63 [95% CI 1.38-1.93], P-trend <0.001), acesulfame-K (HR 1.70 [1.42-2.04], P-trend <0.001), and sucralose (HR 1.34 [1.07-1.69], P-trend = 0.013).</p><p><strong>Conclusions: </strong>Potential for reverse causality cannot be eliminated; however, many sensitivity analyses were computed to limit this and other potential biases. These findings of positive associations between artificial sweetener intakes and increased T2D risk strengthen the evidence that these additives may not be safe sugar alternatives. This study provides important insights in the context of on-going reevaluation of artificial sweeteners by health authorities worldwide.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2023. Diabetes Care 2023;46(Suppl. 1):S49-S67.","authors":"Nuha A ElSayed,&nbsp;Grazia Aleppo,&nbsp;Vanita R Aroda,&nbsp;Raveendhara R Bannuru,&nbsp;Florence M Brown,&nbsp;Dennis Bruemmer,&nbsp;Billy S Collins,&nbsp;Kenneth Cusi,&nbsp;Marisa E Hilliard,&nbsp;Diana Isaacs,&nbsp;Eric L Johnson,&nbsp;Scott Kahan,&nbsp;Kamlesh Khunti,&nbsp;Jose Leon,&nbsp;Sarah K Lyons,&nbsp;Mary Lou Perry,&nbsp;Priya Prahalad,&nbsp;Richard E Pratley,&nbsp;Jane Jeffrie Seley,&nbsp;Robert C Stanton,&nbsp;Robert A Gabbay","doi":"10.2337/dc23-er09a","DOIUrl":"https://doi.org/10.2337/dc23-er09a","url":null,"abstract":"In the section \"Assessment of Comorbidities\" of the article cited above, the subsections \"Hepatitis C Infection,\" \"Pancreatitis,\" \"Fractures,\" \"Sensory Impairment,\" and \"Low Testosterone in Men,\" present in the 2022 guidelines, were inadvertently omitted. The online version of the article (https://doi.org/10.2337/dc23-S004) has been revised to correct the error.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465983/pdf/dc23er09a.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10204996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addendum. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care 2023;46(Suppl. 1):S19-S40.","authors":"Nuha A ElSayed, Grazia Aleppo, Vanita R Aroda, Raveendhara R Bannuru, Florence M Brown, Dennis Bruemmer, Billy S Collins, Marisa E Hilliard, Diana Isaacs, Eric L Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K Lyons, Mary Lou Perry, Priya Prahalad, Richard E Pratley, Jane Jeffrie Seley, Robert C Stanton, Robert A Gabbay","doi":"10.2337/dc23-ad08","DOIUrl":"10.2337/dc23-ad08","url":null,"abstract":"","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552401/pdf/dc23ad08.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addendum. 3. Prevention or Delay of Type 2 Diabetes and Associated Comorbidities: Standards of Care in Diabetes-2023. Diabetes Care 2023;46(Suppl. 1):S41-S48.","authors":"Nuha A ElSayed, Grazia Aleppo, Vanita R Aroda, Raveendhara R Bannuru, Florence M Brown, Dennis Bruemmer, Billy S Collins, Marisa E Hilliard, Diana Isaacs, Eric L Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K Lyons, Mary Lou Perry, Priya Prahalad, Richard E Pratley, Jane Jeffrie Seley, Robert C Stanton, Robert A Gabbay","doi":"10.2337/dc23-ad08a","DOIUrl":"10.2337/dc23-ad08a","url":null,"abstract":"","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552402/pdf/dc23ad08a.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10154857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized Controlled Trial Comparing the Efficacy and Safety of IDegLira Versus Basal-Bolus in Patients With Poorly Controlled Type 2 Diabetes and Very High HbA1c ≥9-15%: DUAL HIGH Trial.","authors":"Rodolfo J Galindo, Bobak Moazzami, Maria F Scioscia, Cesar Zambrano, Bonnie S Albury, Jarrod Saling, Priyathama Vellanki, Francisco J Pasquel, Georgia M Davis, Maya Fayfman, Limin Peng, Guillermo E Umpierrez","doi":"10.2337/dc22-2426","DOIUrl":"10.2337/dc22-2426","url":null,"abstract":"<p><strong>Objective: </strong>In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin.</p><p><strong>Research design and methods: </strong>This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups.</p><p><strong>Results: </strong>Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87).</p><p><strong>Conclusions: </strong>In participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10181407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Insulin Pump Infusion Sites in Type 1 Diabetes: The DERMIS Study.","authors":"Andrea Kalus,&nbsp;Michi M Shinohara,&nbsp;Ruikang Wang,&nbsp;Jesica D Baran,&nbsp;Xiaofu Dong,&nbsp;Dori Khakpour,&nbsp;Jie Lu,&nbsp;Irl B Hirsch","doi":"10.2337/dc23-0426","DOIUrl":"https://doi.org/10.2337/dc23-0426","url":null,"abstract":"<p><strong>Objective: </strong>Continuous subcutaneous insulin infusion (CSII) for type 1 diabetes is increasing in use. Pump site failures are common, but little is known about skin changes from pump use. Using noninvasive optical coherence tomography (OCT), OCT angiography (OCTA), and skin biopsies, we evaluated skin changes from chronic insulin infusion.</p><p><strong>Research design and methods: </strong>In this cross-sectional study, OCT operating at a 1,310-nm central wavelength with a bandwidth of 100 nm was performed immediately before skin punch biopsies were collected at three sites: the current site, with the infusion set removed at time of OCT and biopsy; the recovery site, with the infusion set removed 3 days before biopsy; and the control site, which was never used for any insulin infusion or injection.</p><p><strong>Results: </strong>OCT and OCTA identified characteristics of increased inflammation and vessel density at pump sites compared with control sites. Histologic analysis of pump sites showed differences in skin architecture, including fibrosis, inflammation (including increased tissue eosinophils), and fat necrosis. Immunohistochemical staining showed differences between infusion and control sites regarding staining of ILGF-I and transforming growth factor-β3.</p><p><strong>Conclusions: </strong>These findings support allergic sensitization as a potentially common reaction at CSII sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing. The inflammatory response caused by these common allergic responses may result in tissue changes responsible for the infusion site failures seen frequently in clinical practice.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10098809","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}

{"title":"Rapid Reduction of HbA1c and Early Worsening of Diabetic Retinopathy: A Real-world Population-Based Study in Subjects With Type 2 Diabetes.","authors":"Rafael Simó,&nbsp;Josep Franch-Nadal,&nbsp;Bogdan Vlacho,&nbsp;Jordi Real,&nbsp;Ester Amado,&nbsp;Juana Flores,&nbsp;Manel Mata-Cases,&nbsp;Emilio Ortega,&nbsp;Mercedes Rigla,&nbsp;Joan-Anton Vallés,&nbsp;Cristina Hernández,&nbsp;Didac Mauricio","doi":"10.2337/dc22-2521","DOIUrl":"https://doi.org/10.2337/dc22-2521","url":null,"abstract":"<p><strong>Objective: </strong>Early worsening of diabetic retinopathy (EWDR) due to the rapid decrease of blood glucose levels is a concern in diabetes treatment. The aim of the current study is to evaluate whether this is an important issue in subjects with type 2 diabetes with mild or moderate nonproliferative DR (NPDR), who represent the vast majority of subjects with DR attended in primary care.</p><p><strong>Research design and methods: </strong>This is a retrospective nested case-control study of subjects with type 2 diabetes and previous mild or moderate NPDR. Using the SIDIAP (\"Sistema d'informació pel Desenvolupament de la Recerca a Atenció Primària\") database, we selected 1,150 individuals with EWDR and 1,150 matched control subjects (DR without EWDR). The main variable analyzed was the magnitude of the reduction of HbA1c in the previous 12 months. The reduction of HbA1c was categorized as rapid (>1.5% reduction in <12 months) or very rapid (>2% in <6 months).</p><p><strong>Results: </strong>We did not find any significant difference in HbA1c reduction between case and control subjects (0.13 ± 1.21 vs. 0.21 ± 1.18; P = 0.12). HbA1c reduction did not show significant association with worsening of DR, neither in the unadjusted analyses nor in adjusted statistical models that included the main confounding variables: duration of diabetes, baseline HbA1c, presence of hypertension, and antidiabetic drugs. In addition, when stratification by baseline HbA1c was performed, we did not find that those patients with higher levels of HbA1c presented a higher risk to EWDR.</p><p><strong>Conclusions: </strong>Our results suggest that the rapid reduction of HbA1c is not associated with progression of mild or moderate NPDR.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10100759","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}

{"title":"Bidirectional Mendelian Randomization and Multiphenotype GWAS Show Causality and Shared Pathophysiology Between Depression and Type 2 Diabetes.","authors":"Jared G Maina,&nbsp;Zhanna Balkhiyarova,&nbsp;Arie Nouwen,&nbsp;Igor Pupko,&nbsp;Anna Ulrich,&nbsp;Mathilde Boissel,&nbsp;Amélie Bonnefond,&nbsp;Philippe Froguel,&nbsp;Amna Khamis,&nbsp;Inga Prokopenko,&nbsp;Marika Kaakinen","doi":"10.2337/dc22-2373","DOIUrl":"https://doi.org/10.2337/dc22-2373","url":null,"abstract":"<p><strong>Objective: </strong>Depression is a common comorbidity of type 2 diabetes. We assessed the causal relationships and shared genetics between them.</p><p><strong>Research design and methods: </strong>We applied two-sample, bidirectional Mendelian randomization (MR) to assess causality between type 2 diabetes and depression. We investigated potential mediation using two-step MR. To identify shared genetics, we performed 1) genome-wide association studies (GWAS) separately and 2) multiphenotype GWAS (MP-GWAS) of type 2 diabetes (19,344 case subjects, 463,641 control subjects) and depression using major depressive disorder (MDD) (5,262 case subjects, 86,275 control subjects) and self-reported depressive symptoms (n = 153,079) in the UK Biobank. We analyzed expression quantitative trait locus (eQTL) data from public databases to identify target genes in relevant tissues.</p><p><strong>Results: </strong>MR demonstrated a significant causal effect of depression on type 2 diabetes (odds ratio 1.26 [95% CI 1.11-1.44], P = 5.46 × 10-4) but not in the reverse direction. Mediation analysis indicated that 36.5% (12.4-57.6%, P = 0.0499) of the effect from depression on type 2 diabetes was mediated by BMI. GWAS of type 2 diabetes and depressive symptoms did not identify shared loci. MP-GWAS identified seven shared loci mapped to TCF7L2, CDKAL1, IGF2BP2, SPRY2, CCND2-AS1, IRS1, CDKN2B-AS1. MDD has not brought any significant association in either GWAS or MP-GWAS. Most MP-GWAS loci had an eQTL, including single nucleotide polymorphisms implicating the cell cycle gene CCND2 in pancreatic islets and brain and the insulin signaling gene IRS1 in adipose tissue, suggesting a multitissue and pleiotropic underlying mechanism.</p><p><strong>Conclusions: </strong>Our results highlight the importance to prevent type 2 diabetes at the onset of depressive symptoms and the need to maintain a healthy weight in the context of its effect on depression and type 2 diabetes comorbidity.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Short-Form Measure of Diabetes Distress Among Adults With Type 1 Diabetes for Use in Clinical Practice: Development and Validation of the T1-DDS-7.","authors":"Mette Nygaard,&nbsp;Ingrid Willaing,&nbsp;Lene Eide Joensen,&nbsp;Pil Lindgreen,&nbsp;Vibeke Stenov,&nbsp;Danielle Hessler,&nbsp;Kirsten Nørgaard,&nbsp;Ulrik Pedersen-Bjergaard,&nbsp;Kasper Olesen","doi":"10.2337/dc23-0460","DOIUrl":"https://doi.org/10.2337/dc23-0460","url":null,"abstract":"<p><strong>Objective: </strong>Valid and reliable diabetes distress assessment is essential for identifying adults with elevated levels of concern and to guide targeted support. However, assessing diabetes distress must also be feasible in time-limited settings. We aimed to identify a short-form measure of the 28-item Type 1 Diabetes Distress Scale (T1-DDS-28) representing seven sources of type 1 diabetes distress that would be convenient for use in clinical practice.</p><p><strong>Research design and methods: </strong>Based on the evaluation of influence and importance by 14 experts in diabetes care and research, we identified the best-performing item within each of seven sources of diabetes distress included in the T1-DDS-28. To further validate the proposed short-form measure, we used survey data from 2,016 adults living with type 1 diabetes. Validity was examined by exploratory factor analysis, Cronbach's α, test-retest reliability analysis, and correlations with other psychosocial measures.</p><p><strong>Results: </strong>We identified a short-form measure of the T1-DDS-28 consisting of seven items, each representing a source of diabetes distress. These items showed satisfactory reliability (factor loadings > 0.45; α = 0.82; test-retest correlation, r = 0.90) and validity (correlation with T1-DDS-28, r = 0.95; area under the curve = 0.91; sensitivity 93%; specificity 89%) when combined in the short-form scale (T1-DDS-7).</p><p><strong>Conclusions: </strong>We propose the T1-DDS-7 as a valid and reliable measure for routine screening of diabetes distress among adults with type 1 diabetes. In case of elevated levels of diabetes distress, we recommend that a full-scale assessment and open dialogue follow the short-form measure before determining further treatment.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10102864","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}