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155-OR: Genetic Variation and Time to Progression in TN10 (Teplizumab) 155-OR: TN10(替普珠单抗)的基因变异与病情进展时间
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-155-or
DOMINIKA A. MICHALEK, SUNA ONENGUT-GUMUSCU, WEI-MIN CHEN, TODD M. BRUSKO, ANDREA STECK, PETER GOTTLIEB, RICHARD A. ORAM, JEFFREY KRISCHER, HEMANG M. PARIKH, MARIA J. REDONDO, KEVAN C. HEROLD, STEPHEN S. RICH
Introduction & Objective: TN10 Anti-CD3 Prevention (TN10) was a randomized phase 2 clinical trial that showed teplizumab delayed progression to type 1 diabetes (T1D) in high-risk participants. Both HLA and non-HLA variants could influence time to progression. Here, genome-wide analysis identified variants and pathways that influence time to progression in TN10 participants. Methods: In TN10, relatives with stage 2 T1D (i.e., multiple autoantibodies and dysglycemia) received either teplizumab (N = 44) or placebo (N = 32). Samples were genotyped with a genome-wide array followed by imputation. Cox proportional hazards regression models were used to determine the effect of teplizumab, SNPs, and their interaction on time to progression to stage 3 T1D. Thousands of Polygenic Scores (PGSs) from the PGS catalogue were inferred for each of the TN10 samples, and we identified PGS traits that shared common genetic modifiers with time to progression with teplizumab. Results: A genome-wide analysis identified three loci associated with time to progression (p < 5 x 10-6). Two loci contain genes implicated in the inflammatory response (NFKBIZ) and drug metabolism effect (FMO3). SNP-drug interaction analysis identified four known T1D regions that account for progression differences in teplizumab vs placebo: CCR9 (rs34549672), SH2B3 (rs3184504), UBASH3A (rs9984852), and INS (rs3842761). Within the teplizumab group, novel loci (p < 5 x 10-6) were associated with time to progression, including ZNF385D, CCDC38, SHH, ZNF366, ITPKB and RABGAP1L. Traits with similar genetic contribution to teplizumab time to progression were vitamin B12 (AUC = 0.76) and vitamin D (AUC = 0.72). Conclusions: In individuals with stage 2 T1D, variants in inflammatory, immune-relevant, and drug-responsive genes are associated with teplizumab time to progression. Similarity of the teplizumab-responsive polygenic score with other traits implicate novel pathways that could influence teplizumab treatment. Disclosure D.A. Michalek: None. S. Onengut-Gumuscu: None. W. Chen: None. T.M. Brusko: None. A. Steck: None. P. Gottlieb: Other Relationship; IM Therapeutics. Research Support; Imcyse. Advisory Panel; Imcyse. Consultant; Juvenile Diabetes Research Foundation (JDRF). Research Support; Hemsley Charitable Trust, Novartis AG, Provention Bio, Inc., Precigen, Inc. Advisory Panel; ViaCyte, Inc. Research Support; Nova Pharmaceuticals. R.A. Oram: Research Support; Randox R & D. Consultant; Provention Bio, Inc., Sanofi. J. Krischer: None. H.M. Parikh: None. M.J. Redondo: None. K.C. Herold: Consultant; Sanofi. S.S. Rich: None. Funding National Institutes of Health (1R01DK121843-01)
简介& 目的:TN10 抗 CD3 预防(TN10)是一项随机 2 期临床试验,结果表明替普利珠单抗可延缓高风险参与者发展为 1 型糖尿病(T1D)的时间。HLA和非HLA变异都会影响进展时间。在此,我们通过全基因组分析确定了影响 TN10 参与者病情进展时间的变异和途径。方法在 TN10 中,患有 T1D 2 期(即多种自身抗体和血糖异常)的亲属接受了替普利珠单抗(44 例)或安慰剂(32 例)治疗。使用全基因组阵列对样本进行基因分型,然后进行归因。采用 Cox 比例危险回归模型来确定替普利珠单抗、SNPs 及其交互作用对 T1D 进展到 3 期的时间的影响。我们从 PGS 目录中为每个 TN10 样本推断出了数千个多基因评分 (PGS),并确定了与替普利珠单抗治疗进展时间具有共同遗传修饰因子的 PGS 性状。结果全基因组分析发现了三个与进展时间相关的基因位点(p < 5 x 10-6)。其中两个基因位点包含与炎症反应(NFKBIZ)和药物代谢作用(FMO3)有关的基因。SNP-药物相互作用分析确定了四个已知的 T1D 区域,这些区域导致了替普利珠单抗与安慰剂的进展差异:CCR9(rs34549672)、SH2B3(rs3184504)、UBASH3A(rs9984852)和INS(rs3842761)。在替普利珠单抗组中,ZNF385D、CCDC38、SHH、ZNF366、ITPKB和RABGAP1L等新基因位点(p < 5 x 10-6)与疾病进展时间相关。维生素 B12(AUC = 0.76)和维生素 D(AUC = 0.72)等性状对替普利珠单抗的病情进展时间具有相似的遗传贡献。结论在 T1D 2 期患者中,炎症基因、免疫相关基因和药物反应基因的变异与替普利珠单抗的病情进展时间相关。替普利珠单抗反应性多基因评分与其他性状的相似性意味着可能影响替普利珠单抗治疗的新途径。披露 D.A. Michalek:无。S. Onengut-Gumuscu: 无。W. Chen: None.T.M. Brusko:无:无。A. Steck:无。P. Gottlieb:其他关系;IM Therapeutics。研究支持;Imcyse.顾问团;Imcyse.顾问;青少年糖尿病研究基金会 (JDRF)。研究支持;Hemsley 慈善信托基金、诺华股份公司、Provention Bio, Inc.、Precigen, Inc.顾问团;ViaCyte, Inc.研究支持;Nova Pharmaceuticals。R.A. Oram:研究支持;Randox R &;D. 顾问;Provention Bio, Inc.、赛诺菲。J. Krischer:无。H.M. Parikh:无:无。M.J. Redondo:无。K.C. Herold:赛诺菲顾问。S.S. Rich:无。美国国立卫生研究院(1R01DK121843-01)资助
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引用次数: 0
348-OR: Multiancestry Whole Genome Sequencing (WGS) Meta-analysis to Identify Loci Associated with Imaging-Measured Hepatic Steatosis 348-OR: 通过多家畜全基因组测序(WGS)元分析确定与成像测量的肝脏脂肪变性相关的基因位点
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-348-or
NICHOLETTE ALLRED, CHINMAY RAUT, YANHUA CHEN, ANTONINO OLIVERI, JEFFREY O'CONNELL, KATHLEEN RYAN, JEROME I. ROTTER, STEPHEN S. RICH, AARON HAKIM, PATRICIA PEYSER, LAWRENCE F. BIELAK, CHING-TI LIU, JAMES G. TERRY, MYRIAM FORNAGE, LYNNE E. WAGENKNECHT, ELIZABETH K. SPELIOTES, NHLBI TRANS-OMICS FOR PRECISION MEDICINE (TOPMED)PROGRAM, GOLD CONSORTIUM
Introduction and Objective: Steatotic liver disease, formerly called non-alcoholic fatty liver disease (NAFLD), is the most common cause of chronic liver disease worldwide; yet, few effective methods for prevention/treatment exist making it one of the biggest unmet public health needs of our time. To date, genetic studies have been limited to identifying common variants in predominantly European-ancestry populations or focused on surrogate phenotypes, e.g. liver enzymes, identifying association with comorbidities. Here we present a multi-ancestry whole genome sequencing (WGS) association study to discover rare variants associated with imaging-measured hepatic steatosis. Methods: Study-, ancestry- and sex-stratified association analyses were conducted using SAIGEgds in nine studies with imaging-measured hepatic steatosis adjusted for age, sex, alcoholic drinks per week and principal component estimates of admixture. Stratified results were meta-analyzed using a fixed-effects model. Cochran’s Q-test and the I2 metric were used to estimate heterogeneity. Results: Meta-analyses included 23,156 European, African, Hispanic and Chinese ancestry individuals and identified five significant loci (P<5x10-08): PNPLA3, PPP1R3B, HAPLN4, intergenic region on chr14 and F11-AS1. Nine additional variants trended toward association (P<5x10-07). Sex-stratified meta-analyses revealed additional associations in an intergenic region on chr10, RP11-115J16.1 and UBE3B. Variants in RP11-115J16.1 remained significant in European ancestry samples. Significantly associated variants in SLC2A1-AS1 and LINC01684 were novel loci in African Americans. Conclusion: Taken together, multi-ancestry analysis of imaging-measured hepatic steatosis using WGS replicated previously associated loci and identified novel sex- and ancestry-specific loci. Functional studies are underway to determine the biological impact of these findings. Disclosure N. Allred: None. C. Raut: None. Y. Chen: None. A. Oliveri: None. J. O'Connell: None. K. Ryan: None. J.I. Rotter: None. S.S. Rich: None. A. Hakim: None. P. Peyser: None. L.F. Bielak: None. C. Liu: None. J.G. Terry: None. M. Fornage: None. L.E. Wagenknecht: None. E.K. Speliotes: Other Relationship; University of Michigan. Funding National Institute of Diabetes and Digestive Kidney Disease (R01 DK128871)
导言和目标:脂肪肝,以前称为非酒精性脂肪肝(NAFLD),是全球最常见的慢性肝病;然而,几乎没有有效的预防/治疗方法,使其成为当代最大的未满足公共卫生需求之一。迄今为止,遗传学研究仅限于在以欧洲血统为主的人群中确定常见变体,或侧重于替代表型(如肝酶),以确定与合并症的关联。在此,我们介绍一项多安塞斯特全基因组测序(WGS)关联研究,以发现与成像测量的肝脂肪变性相关的罕见变异。研究方法使用 SAIGEgds 对九项影像测量肝脂肪变性的研究进行了研究、祖先和性别分层关联分析,并对年龄、性别、每周酒精饮品量和主成分混杂估计值进行了调整。采用固定效应模型对分层结果进行了元分析。Cochran's Q 检验和 I2 指标用于估计异质性。结果元分析纳入了 23156 名欧洲、非洲、西班牙和中国血统的个体,并确定了五个重要的基因位点(P<5x10-08):PNPLA3、PPP1R3B、HAPLN4、chr14上的基因间区域和F11-AS1。另有 9 个变异具有关联趋势(P<5x10-07)。性别分层荟萃分析表明,在 chr10 上的基因间区域、RP11-115J16.1 和 UBE3B 中存在其他关联。在欧洲血统样本中,RP11-115J16.1 的变异仍然显著。在非裔美国人中,SLC2A1-AS1 和 LINC01684 的显著相关变异是新的位点。结论总之,利用 WGS 对成像测量的肝脂肪变性进行的多种姓分析复制了以前的相关位点,并发现了新的性别和祖先特异性位点。目前正在进行功能研究,以确定这些发现的生物学影响。披露 N. Allred:无。C. Raut:无。Y. Chen: None.A. Oliveri: None.J. O'Connell: None.K. Ryan: None.J.I. Rotter:J.I. Rotter: None.S.S. Rich: None.A. Hakim:无。P. Peyser:无。L.F. Bielak:无。C. Liu: None.J.G. Terry: 无:无。M. Fornage:无。L.E. Wagenknecht:无:无。E.K. Speliotes:其他关系;密歇根大学。资助国家糖尿病和消化性肾病研究所 (R01 DK128871)
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引用次数: 0
1301-P: Frequency of Single Autoantibody Positivity (SAB+) Varies by Race/Ethnicity and Area Deprivation Index in Individuals at Risk for Type 1 Diabetes (T1D) 1301-P:1 型糖尿病 (T1D) 高危人群中单一自身抗体阳性 (SAB+) 的频率因种族/族裔和地区贫困指数而异
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-1301-p
ANANTA ADDALA, SUSANNE M. CABRERA, DAVID D. CUTHBERTSON, INGRID LIBMAN, MUSTAFA TOSUR, ALEJANDRO F. SILLER, LINDA A. DIMEGLIO, KEVAN C. HEROLD, MARIA J. REDONDO, HEBA M. ISMAIL
Introduction & Objective: The diversity of individuals living with T1D has increased, driven by Hispanic (H) and non-Hispanic Black (NHB) populations. Yet, whether H and NHB populations have different rates of SAB+ than other groups, which can impact clinical care and research opportunities, has not been well characterized. Area deprivation and race/ethnicity are strongly associated with each other and have compounding and adverse effects on diabetes-related health outcomes. We examined TrialNet data from relatives of persons with T1D screened for pancreatic autoantibodies and evaluated the frequency of SAB+ by race/ethnicity and area deprivation. Methods: Persons (n=28330) screened between 4/9/19-12/31/22 were included. Race/ethnicity was categorized as non-Hispanic white (NHW), H, NHB, and non-Hispanic other (NHO). Home address zip codes were used to assign an Area Deprivation Index, a Health and Human Services Administration index incorporating neighborhood income, education, employment, and housing that ranges from 1 (least deprived) to 100 (most deprived). Deprivation was analyzed in quintiles. Results: A majority (80.7%) self-identified as NHW; fewer as H (9.8%), NHB (2.5%), and NHO (7.0%). Deprivation differed by race/ethnicity (NHW 46±23, H: 45±24, NHB: 53±23, and NHO: 39±25, p<0.001). SAB+ was more common in NHB and H than NHO and NHW individuals (Overall: 3.0%, NHB: 4.7%, H: 3.8%, NHO: 3.1%, NWH: 3.0%; χ2 p=0.02). Logistic regression identified a linear relationship between SAB+ and deprivation (Deprivation quintiles 1 to 5: 2.9%, 2.7%, 3.1%, 3.1%, 3.5%; p=0.04). Conclusion: These data suggest SAB+ status varies by both race/ethnicity and deprivation which warrants further investigation. Understanding patterns of autoantibody positivity that occur in diverse populations at risk for T1D is foundational to identifying persons who are SAB+ or in early stages of T1D who may now be eligible for preventive therapies. Disclosure A. Addala: None. S.M. Cabrera: Research Support; Abbott. D.D. Cuthbertson: None. I. Libman: None. M. Tosur: None. A.F. Siller: None. L.A. DiMeglio: Research Support; Dompé, Lilly Diabetes, MannKind Corporation, Medtronic, Provention Bio, Inc., Sanofi, Zealand Pharma A/S, Amgen Inc. Advisory Panel; Vertex Pharmaceuticals Incorporated, Abata Therapeutics. K.C. Herold: Consultant; Sanofi. M.J. Redondo: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics.
引言& 目的:在西班牙裔(H)和非西班牙裔黑人(NHB)人群的推动下,T1D 患者的多样性有所增加。然而,西班牙裔和非西班牙裔黑人的 SAB+ 患病率是否有别于其他群体,这可能会影响临床护理和研究机会,目前还没有很好的定性。地区贫困和种族/人种密切相关,并对糖尿病相关的健康结果产生复合的不利影响。我们研究了 TrialNet 数据,这些数据来自接受胰腺自身抗体筛查的 T1D 患者的亲属,并根据种族/民族和地区贫困程度评估了 SAB+ 的频率。方法:纳入在 4/9/19-12/31/22 期间接受筛查的人(n=28330)。种族/族裔分为非西班牙裔白人 (NHW)、H、NHB 和非西班牙裔其他 (NHO)。家庭住址的邮政编码被用来分配地区贫困指数,该指数是卫生与公众服务管理局(Health and Human Services Administration)综合了社区收入、教育、就业和住房的指数,范围从 1(最贫困)到 100(最贫困)。贫困程度按五等分进行分析。结果显示大多数人(80.7%)自我认同为 NHW;较少人认同为 H(9.8%)、NHB(2.5%)和 NHO(7.0%)。不同种族/族裔的贫困程度不同(NHW 46±23,H:45±24,NHB:53±23,NHO:39±25,p<0.001)。与 NHO 和 NHW 相比,SAB+ 在 NHB 和 H 中更为常见(总体:3.0%,NHB:4.7%,H:3.8%,NHO:3.1%,NWH:3.0%;χ2 p=0.02)。逻辑回归确定了 SAB+ 与贫困之间的线性关系(贫困五分位数 1 至 5:2.9%、2.7%、3.1%、3.1%、3.5%;P=0.04)。结论这些数据表明,SAB+状态因种族/民族和贫困程度而异,值得进一步研究。了解不同T1D高危人群自身抗体阳性的模式,对于识别SAB+患者或T1D早期患者(他们现在可能有资格接受预防性治疗)至关重要。披露 A. Addala:无。S.M. Cabrera:研究支持;雅培。D.D. Cuthbertson:无:无。I. Libman: None.M. Tosur:M. Tosur: None.A.F. Siller:无。L.A. DiMeglio:研究支持;Dompé、Lilly Diabetes、MannKind Corporation、Medtronic、Provention Bio, Inc.、Sanofi、Zealand Pharma A/S、Amgen Inc.顾问团;Vertex Pharmaceuticals Incorporated、Abata Therapeutics。K.C. Herold:赛诺菲顾问。M.J. Redondo:无。H.M. Ismail:顾问;赛诺菲、Rise Therapeutics。
{"title":"1301-P: Frequency of Single Autoantibody Positivity (SAB+) Varies by Race/Ethnicity and Area Deprivation Index in Individuals at Risk for Type 1 Diabetes (T1D)","authors":"ANANTA ADDALA, SUSANNE M. CABRERA, DAVID D. CUTHBERTSON, INGRID LIBMAN, MUSTAFA TOSUR, ALEJANDRO F. SILLER, LINDA A. DIMEGLIO, KEVAN C. HEROLD, MARIA J. REDONDO, HEBA M. ISMAIL","doi":"10.2337/db24-1301-p","DOIUrl":"https://doi.org/10.2337/db24-1301-p","url":null,"abstract":"Introduction & Objective: The diversity of individuals living with T1D has increased, driven by Hispanic (H) and non-Hispanic Black (NHB) populations. Yet, whether H and NHB populations have different rates of SAB+ than other groups, which can impact clinical care and research opportunities, has not been well characterized. Area deprivation and race/ethnicity are strongly associated with each other and have compounding and adverse effects on diabetes-related health outcomes. We examined TrialNet data from relatives of persons with T1D screened for pancreatic autoantibodies and evaluated the frequency of SAB+ by race/ethnicity and area deprivation. Methods: Persons (n=28330) screened between 4/9/19-12/31/22 were included. Race/ethnicity was categorized as non-Hispanic white (NHW), H, NHB, and non-Hispanic other (NHO). Home address zip codes were used to assign an Area Deprivation Index, a Health and Human Services Administration index incorporating neighborhood income, education, employment, and housing that ranges from 1 (least deprived) to 100 (most deprived). Deprivation was analyzed in quintiles. Results: A majority (80.7%) self-identified as NHW; fewer as H (9.8%), NHB (2.5%), and NHO (7.0%). Deprivation differed by race/ethnicity (NHW 46±23, H: 45±24, NHB: 53±23, and NHO: 39±25, p<0.001). SAB+ was more common in NHB and H than NHO and NHW individuals (Overall: 3.0%, NHB: 4.7%, H: 3.8%, NHO: 3.1%, NWH: 3.0%; χ2 p=0.02). Logistic regression identified a linear relationship between SAB+ and deprivation (Deprivation quintiles 1 to 5: 2.9%, 2.7%, 3.1%, 3.1%, 3.5%; p=0.04). Conclusion: These data suggest SAB+ status varies by both race/ethnicity and deprivation which warrants further investigation. Understanding patterns of autoantibody positivity that occur in diverse populations at risk for T1D is foundational to identifying persons who are SAB+ or in early stages of T1D who may now be eligible for preventive therapies. Disclosure A. Addala: None. S.M. Cabrera: Research Support; Abbott. D.D. Cuthbertson: None. I. Libman: None. M. Tosur: None. A.F. Siller: None. L.A. DiMeglio: Research Support; Dompé, Lilly Diabetes, MannKind Corporation, Medtronic, Provention Bio, Inc., Sanofi, Zealand Pharma A/S, Amgen Inc. Advisory Panel; Vertex Pharmaceuticals Incorporated, Abata Therapeutics. K.C. Herold: Consultant; Sanofi. M.J. Redondo: None. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730475","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}
引用次数: 0
235-OR: Quality of Life and Health Utility 12 Years after Randomization to Bariatric Surgery vs. Medical Therapy in Patients with Type 2 Diabetes and Obesity—The ARMMS-T2D Study 235-OR:2 型糖尿病和肥胖症患者随机接受减肥手术与药物治疗 12 年后的生活质量和健康效用--ARMMS-T2D 研究
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-235-or
DONALD C. SIMONSON, WILLIAM F. GOURASH, DAVID ARTERBURN, BO HU, SANGEETA R. KASHYAP, MARY-ELIZABETH PATTI, PHILIP SCHAUER, DAVID E. CUMMINGS, ANITA COURCOULAS, ALI AMINIAN, JOHN M. JAKICIC, ASHLEY H. VERNON, JOHN P. KIRWAN
Introduction & Objective: T2D and obesity are associated with reduced quality of life (QoL) and health utility (HU), but long-term effects of metabolic/bariatric surgery (MBS) vs. a medical/lifestyle intervention (MLI) on these outcomes are not known. Methods: We studied 228 patients with T2D and obesity who were randomized to MBS (RYGB, gastric band, or sleeve gastrectomy; n = 152) vs. MLI (n = 76) in the ARMMS-T2D study. QoL (SF-36; including Physical Component Score [PCS], Mental Component Score [MCS], and 8 scale scores) and HU (SF-6D) were measured annually for 12 yrs. Results: At baseline, age = 49.2 ± 8.0 yrs., 68% were female, 68% White, BMI = 36.3 ± 3.4 kg/m², HbA1c = 8.7 ± 1.6%. PCS improved significantly in MBS at year 1, remained higher vs. MLI over 12 yrs. (p < 0.001), and was associated with better general health (p < 0.001), physical function (p = 0.001), energy (p = 0.003), and reduced pain (p = 0.03). Change in BMI was greater after MBS vs. MLI (-18.6 ± 12.4% vs. -11.4 ± 10.9%, p < 0.001), and significantly correlated with change in PCS (r = -0.43, p < 0.001). In contrast, MCS (p = 0.14), emotional well-being (p = 0.53), role emotional (p = 0.43), and social functioning (p = 0.11) did not change from baseline and were similar between groups over 12 yrs. Changes in PCS and MCS were not associated with change in HbA1c. Among patients taking insulin at baseline, those who discontinued insulin had higher PCS (p < 0.001) over time. HU was moderately low at baseline (0.69 ± 0.08) and did not change significantly in either group during 12 yrs. Conclusions: MBS produced sustained weight loss that correlated with improved PCS, including better general health, physical function, energy, and less pain. PCS improved more in patients who discontinued insulin. There were no significant differences between groups over time in MCS or in HU. These differences may help patients with T2D and obesity make informed decisions about their best treatment options. Disclosure D.C. Simonson: Stock/Shareholder; Phase V Technologies, Inc. Advisory Panel; GI Windows. W.F. Gourash: None. D. Arterburn: None. B. Hu: None. S.R. Kashyap: Research Support; Fractyl Health, Inc. Advisory Panel; GI Dynamics. Research Support; Janssen Pharmaceuticals, Inc. M. Patti: Research Support; Dexcom, Inc. Consultant; Hanmi Pharm. Co., Ltd., MBX Biosciences. Other Relationship; Fractyl Health, Inc. Consultant; AstraZeneca, Spruce Biosciences. P. Schauer: Research Support; Ethicon, Inc. Other Relationship; Ethicon, Inc. Research Support; Medtronic. Other Relationship; Medtronic, Novo Nordisk. Advisory Panel; Lilly Diabetes, GI Dynamics, Heron. Stock/Shareholder; Mediflix, SE Healthcare. Other Relationship; Klens. Advisory Panel; Persona, Keyron. Stock/Shareholder; Metabolic Health International LTD. D.E. Cummings: None. A. Courcoulas: Research Support; Allurion, Eli Lilly and Company. A. Aminian: Research Support; Medtronic. Consultant; Medt
导言& 目的:T2D和肥胖与生活质量(QoL)和健康效用(HU)降低有关,但代谢/减肥手术(MBS)与医疗/生活方式干预(MLI)对这些结果的长期影响尚不清楚。研究方法我们对 ARMMS-T2D 研究中随机接受 MBS(RYGB、胃束带或袖状胃切除术;n = 152)与 MLI(n = 76)治疗的 228 名 T2D 和肥胖症患者进行了研究。在长达 12 年的时间里,每年测量一次 QoL(SF-36;包括身体成分评分 [PCS]、心理成分评分 [MCS] 和 8 个量表评分)和 HU(SF-6D)。结果显示基线年龄 = 49.2 ± 8.0 岁,68% 为女性,68% 为白人,体重指数 = 36.3 ± 3.4 kg/m²,血红蛋白 A1c = 8.7 ± 1.6%。MBS 的 PCS 在第 1 年有明显改善,12 年后仍高于 MLI(pamp &;lt;0.001),并与总体健康状况改善(pamp &;lt;0.001)、身体功能改善(p = 0.001)、精力充沛(p = 0.003)和疼痛减轻(p = 0.03)相关。MBS 与 MLI 相比,BMI 的变化更大(-18.6 ± 12.4% vs. -11.4 ± 10.9%,p &;lt;0.001),并且与 PCS 的变化显著相关(r = -0.43,p &;lt;0.001)。相比之下,MCS(p = 0.14)、情绪幸福感(p = 0.53)、角色情感(p = 0.43)和社会功能(p = 0.11)与基线相比没有变化,并且在 12 年中各组之间的情况相似。PCS 和 MCS 的变化与 HbA1c 的变化无关。在基线时服用胰岛素的患者中,随着时间的推移,停用胰岛素的患者的 PCS 较高(p < 0.001)。HU 在基线时为中等偏低(0.69 ± 0.08),12 年间两组患者的 HU 均无显著变化。结论:多巴胺苯丙胺类兴奋剂能持续减轻体重,并改善患者的 PCS,包括改善一般健康状况、身体机能、精力和减轻疼痛。停用胰岛素的患者的 PCS 改善幅度更大。随着时间的推移,各组之间在 MCS 或 HU 方面没有明显差异。这些差异可能有助于患有 T2D 和肥胖症的患者就最佳治疗方案做出明智的决定。披露 D.C. Simonson:股票/股东;Phase V Technologies, Inc.顾问小组;GI Windows。W.F. Gourash:无。D. Arterburn:无:无。B. Hu:无。S.R. Kashyap:研究支持;Fractyl Health, Inc.顾问团;GI Dynamics.研究支持;Janssen Pharmaceuticals, Inc.M. Patti:研究支持;Dexcom, Inc.顾问;Hanmi Pharm.Co., Ltd., MBX Biosciences.其他关系;Fractyl Health, Inc.顾问;AstraZeneca、Spruce Biosciences。P. Schauer:研究支持;Ethicon, Inc.其他关系;Ethicon, Inc.研究支持;Medtronic.其他关系;美敦力、诺和诺德。顾问团;礼来糖尿病、GI Dynamics、Heron。股票/股东;Mediflix、SE Healthcare。其他关系;Klens。顾问团;Persona、Keyron。股票/股东;Metabolic Health International LTD.D.E. Cummings:无。A. Courcoulas:研究支持;Allurion、礼来公司。A. Aminian:研究支持;美敦力。顾问;美敦力、Ethicon, Inc.研究支持;Ethicon, Inc.顾问团;礼来公司。J.M. Jakicic:研究支持;Epitomee。顾问团;Wondr Health。顾问;Education Initiatives, Inc.A.H. Vernon:无。J.P. Kirwan:无。资助国立卫生研究院(U01 DK114156)
{"title":"235-OR: Quality of Life and Health Utility 12 Years after Randomization to Bariatric Surgery vs. Medical Therapy in Patients with Type 2 Diabetes and Obesity—The ARMMS-T2D Study","authors":"DONALD C. SIMONSON, WILLIAM F. GOURASH, DAVID ARTERBURN, BO HU, SANGEETA R. KASHYAP, MARY-ELIZABETH PATTI, PHILIP SCHAUER, DAVID E. CUMMINGS, ANITA COURCOULAS, ALI AMINIAN, JOHN M. JAKICIC, ASHLEY H. VERNON, JOHN P. KIRWAN","doi":"10.2337/db24-235-or","DOIUrl":"https://doi.org/10.2337/db24-235-or","url":null,"abstract":"Introduction & Objective: T2D and obesity are associated with reduced quality of life (QoL) and health utility (HU), but long-term effects of metabolic/bariatric surgery (MBS) vs. a medical/lifestyle intervention (MLI) on these outcomes are not known. Methods: We studied 228 patients with T2D and obesity who were randomized to MBS (RYGB, gastric band, or sleeve gastrectomy; n = 152) vs. MLI (n = 76) in the ARMMS-T2D study. QoL (SF-36; including Physical Component Score [PCS], Mental Component Score [MCS], and 8 scale scores) and HU (SF-6D) were measured annually for 12 yrs. Results: At baseline, age = 49.2 ± 8.0 yrs., 68% were female, 68% White, BMI = 36.3 ± 3.4 kg/m², HbA1c = 8.7 ± 1.6%. PCS improved significantly in MBS at year 1, remained higher vs. MLI over 12 yrs. (p < 0.001), and was associated with better general health (p < 0.001), physical function (p = 0.001), energy (p = 0.003), and reduced pain (p = 0.03). Change in BMI was greater after MBS vs. MLI (-18.6 ± 12.4% vs. -11.4 ± 10.9%, p < 0.001), and significantly correlated with change in PCS (r = -0.43, p < 0.001). In contrast, MCS (p = 0.14), emotional well-being (p = 0.53), role emotional (p = 0.43), and social functioning (p = 0.11) did not change from baseline and were similar between groups over 12 yrs. Changes in PCS and MCS were not associated with change in HbA1c. Among patients taking insulin at baseline, those who discontinued insulin had higher PCS (p < 0.001) over time. HU was moderately low at baseline (0.69 ± 0.08) and did not change significantly in either group during 12 yrs. Conclusions: MBS produced sustained weight loss that correlated with improved PCS, including better general health, physical function, energy, and less pain. PCS improved more in patients who discontinued insulin. There were no significant differences between groups over time in MCS or in HU. These differences may help patients with T2D and obesity make informed decisions about their best treatment options. Disclosure D.C. Simonson: Stock/Shareholder; Phase V Technologies, Inc. Advisory Panel; GI Windows. W.F. Gourash: None. D. Arterburn: None. B. Hu: None. S.R. Kashyap: Research Support; Fractyl Health, Inc. Advisory Panel; GI Dynamics. Research Support; Janssen Pharmaceuticals, Inc. M. Patti: Research Support; Dexcom, Inc. Consultant; Hanmi Pharm. Co., Ltd., MBX Biosciences. Other Relationship; Fractyl Health, Inc. Consultant; AstraZeneca, Spruce Biosciences. P. Schauer: Research Support; Ethicon, Inc. Other Relationship; Ethicon, Inc. Research Support; Medtronic. Other Relationship; Medtronic, Novo Nordisk. Advisory Panel; Lilly Diabetes, GI Dynamics, Heron. Stock/Shareholder; Mediflix, SE Healthcare. Other Relationship; Klens. Advisory Panel; Persona, Keyron. Stock/Shareholder; Metabolic Health International LTD. D.E. Cummings: None. A. Courcoulas: Research Support; Allurion, Eli Lilly and Company. A. Aminian: Research Support; Medtronic. Consultant; Medt","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730484","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}
引用次数: 0
349-OR: Reduction of RNA-Editing Enzyme ADAR1 in Human Islets Triggers an Interferon Response and Impairs Beta-Cell Function 349-OR:人胰岛中的 RNA 编辑酶 ADAR1 减少会引发干扰素反应并损害 Beta 细胞功能
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-349-or
CHUNHUA DAI, AJAY K. SINGH, REBEKAH BRANTLEY, AMBER BRADLEY, REGINA JENKINS, DIANE C. SAUNDERS, MARCELA BRISSOVA, EREZ LEVANON, AGNES KLOCHENDLER, YUVAL DOR, ALVIN C. POWERS
Introduction & Objective: It is thought that viral infection triggers islet inflammation, an interferon signature, and autoimmunity resulting in type 1 diabetes. Despite extensive research, an inciting virus has not been identified. We hypothesized that impaired RNA editing and accumulation of double-stranded RNA in beta cells triggers an interferon response, causing islet inflammation, autoimmunity, and beta cell destruction. While RNA editing regulated by adenosine deaminases acting on RNA (ADAR) has been studied in some organs and in cancer, little is known about the role of ADAR in human islets. Method: To elucidate the role of ADAR1 in human islets, we first studied ADAR expression and distribution in human pancreas across postnatal developmental timeline (1 day, 4 months, 2, 6, 10, 35 years). Then we transduced human pseudoislets with a shRNA for ADAR and examined their function and gene expression. The transduced pseudoislets were also transplanted into NSG mice. Insulin secretion was measured and grafts were studied. Results: We found that ADAR1 expression at all ages was greater in endocrine cells than acinar cells. Using the shRNA approach, ADAR mRNA levels were reduced by 70% (n=11 donors). After 7-day culture, expression of dsRNA sensors, IFNB1, IRF7, IRF9, and interferon-stimulated genes was increased while INS and MAFA expression was reduced in ADAR knockdown islets without changes in insulin secretion. However, 3 weeks post transplantation, glucose/arginine-stimulated human insulin secretion was significantly decreased in mice with the ADAR shRNA graft compared with scrambled shRNA control graft (0.117 vs 0.300 ng/mL, p=0.0001, n=3 donors). Analysis of pseudoislet grafts 4 weeks after transplantation showed marked accumulation of mouse CD45+ cells around ADAR-knockdown islet grafts. Conclusion: Interruption of RNA editing in human islets activates the interferon signaling pathway leading to islet inflammation and beta cell dysfunction. Disclosure C. Dai: None. A.K. Singh: None. R. Brantley: None. A. Bradley: None. R. Jenkins: None. D.C. Saunders: None. M. Brissova: None. E. Levanon: Advisory Panel; ADARX, Exsilio. A. Klochendler: None. Y. Dor: None. A.C. Powers: None.
导言与目标:人们认为病毒感染会引发胰岛炎症、干扰素特征和自身免疫,从而导致 1 型糖尿病。尽管进行了大量研究,但仍未找到诱发病毒。我们假设,RNA 编辑功能受损和双链 RNA 在 beta 细胞中的积累会引发干扰素反应,导致胰岛炎症、自身免疫和 beta 细胞破坏。虽然在一些器官和癌症中研究了由作用于 RNA 的腺苷脱氨酶(ADAR)调控的 RNA 编辑,但对 ADAR 在人类胰岛中的作用却知之甚少。方法:为了阐明 ADAR1 在人胰岛中的作用,我们首先研究了 ADAR 在人胰岛中的表达和分布,研究时间跨越了人出生后的发育时间线(1 天、4 个月、2、6、10、35 年)。然后,我们用针对 ADAR 的 shRNA 转导了人假性小胰岛,并研究了它们的功能和基因表达。我们还将转导的假小体移植到 NSG 小鼠体内。对胰岛素分泌进行了测量,并对移植物进行了研究。结果:我们发现,在所有年龄段,ADAR1 在内分泌细胞中的表达均高于在尖突细胞中的表达。使用 shRNA 方法,ADAR mRNA 水平降低了 70%(n=11 供体)。培养7天后,dsRNA传感器、IFNB1、IRF7、IRF9和干扰素刺激基因的表达增加,而ADAR基因敲除的胰岛细胞中INS和MAFA的表达减少,但胰岛素分泌没有变化。然而,移植后 3 周,与乱码 shRNA 对照移植相比,使用 ADAR shRNA 移植的小鼠葡萄糖/精氨酸刺激的人胰岛素分泌明显减少(0.117 vs 0.300 ng/mL,p=0.0001,n=3 供体)。移植 4 周后对假性小鼠移植物的分析显示,ADAR 敲除的小鼠胰岛移植物周围有明显的小鼠 CD45+ 细胞聚集。结论人胰岛中 RNA 编辑的中断会激活干扰素信号通路,导致胰岛炎症和 beta 细胞功能障碍。披露 C. Dai:无。A.K. Singh:无。R. Brantley:无。A. Bradley:无。R. Jenkins:无。D.C. Saunders:无。M. Brissova:无。E. Levanon:顾问小组;ADARX、Exsilio。A. Klochendler:无:无。Y. Dor:无。A.C. Powers:无。
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引用次数: 0
1135-P: Pigment Epithelium–Derived Factor, Diabetic Kidney Disease, and Hypertension—Deciphering the Proteomic Response to Metabolic Bariatric Surgery in Adolescents 1135-P:色素上皮衍生因子、糖尿病肾病和高血压--解读蛋白质组对青少年代谢减肥手术的反应
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-1135-p
PHOOM NARONGKIATIKHUN, YE JI CHOI, NHUNG NGUYEN, KELLY NASH, KALIE L. TOMMERDAHL, MATTHIAS KRETZLER, THOMAS INGE, JUSTIN R. RYDER, LAURA PYLE, PETTER BJORNSTAD
Introduction & Objective: This study aims to explore the effects of metabolic bariatric surgery (MBS) on plasma proteins linked to diabetic kidney disease and hypertension in youth with type 2 diabetes (T2D). Methods: We measured 7604 proteins in 326 plasma samples from severely obese youth, both with and without T2D, in the Teen-LABS study, examining pre- and post-MBS changes (6 month, 1, 2-, 3-, 4-, and 5-year follow-up). This analysis focused on proteins identified in the TODAY cohort as predictors of severe albuminuria (ACR ≥300 mg/g) and hypertension (SBP≥130/80 mm Hg), in youth with T2D (n=374), using Cox proportional hazard models adjusted for age, sex, HbA1c, log-transformed triglycerides and estimated insulin sensitivity. A mixed model evaluated proteomic changes post-MBS, maintaining a 5% false discovery rate with reported q-values. Results: In Teen-LABS, several proteins associated with a higher risk of severe albuminuria and hypertension in TODAY showed notable post-surgical downregulation. Higher pigment epithelium-derived factor (PEDF) at baseline predicted onset to severe albuminuria (HR: 1.63, 95% CI 1.12, 2.37, per 1 SD increment) and hypertension (HR: 1.41, 95% CI 1.22, 1.63, per 1 SD increment) over 15 years in TODAY after multivariable adjustments. In Teen-LABS, PEDF decreased post-MBS compared to baseline at 6 months follow-up (logFC: -0.30, q-value=1.24x10-31), year 1 (logFC: -0.28, q-value=2.35x10-29), year 2 (logFC: -0.32, q-value=1.85x10-34), year 3 (logFC: -0.28, q-value=6.95x10-29), year 4 (logFC: -0.30, q-value=4.13x10-28) and year 5 (logFC: -0.30, q-value=2.78x10-26). Conclusion: These analyses show durable attenuation of plasma PEDF after MBS, a protein strongly associated with risk of severe albuminuria and hypertension in youth with T2D. PEDF is implicated in endothelial dysfunction and vascular damage through impaired angiogenesis and endothelial repair mechanisms. Disclosure P. Narongkiatikhun: None. Y. Choi: None. N. Nguyen: None. K. Nash: None. K.L. Tommerdahl: None. M. Kretzler: Research Support; Boehringer-Ingelheim, Certa, Traveere Pharmaceuticals, Maze Therapeutics, Roche Pharmaceuticals, AstraZeneca, Novo Nordisk, Moderna, Inc., Chinook Therapeutics Inc., angion, Lilly Diabetes, Renalytix, Gilead Sciences, Inc., Regeneron Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex. J.R. Ryder: None. L. Pyle: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. Funding National Institutes of Health
引言& 目的:本研究旨在探讨代谢减重手术(MBS)对2型糖尿病(T2D)患者血浆中与糖尿病肾病和高血压有关的蛋白质的影响。研究方法我们测量了 Teen-LABS 研究中 326 份严重肥胖青少年血浆样本中的 7604 种蛋白质,其中既有 T2D 患者,也有非 T2D 患者,并检查了减重手术前后(6 个月、1 年、2 年、3 年、4 年和 5 年随访)的变化。这项分析的重点是在 TODAY 队列中发现的可预测患有 T2D 的青少年(人数=374)严重白蛋白尿(ACR ≥300 mg/g)和高血压(SBP ≥130/80 mm Hg)的蛋白质,使用的是经年龄、性别、HbA1c、对数变换甘油三酯和估计胰岛素敏感性调整的 Cox 比例危险模型。混合模型评估了MBS后蛋白质组的变化,报告的q值保持了5%的误发现率。结果在 Teen-LABS 中,与 TODAY 中严重白蛋白尿和高血压风险较高相关的几种蛋白质在手术后出现了明显的下调。经多变量调整后,基线色素上皮衍生因子(PEDF)越高,预示 TODAY 15 年后会出现严重白蛋白尿(HR:1.63,95% CI 1.12,2.37,每 1 SD 增量)和高血压(HR:1.41,95% CI 1.22,1.63,每 1 SD 增量)。在 Teen-LABS 中,MBS 后与基线相比,PEDF 在 6 个月随访(logFC:-0.30,q-value=1.24x10-31)、第 1 年(logFC:-0.28,q-value=2.35x10-29)、第 2 年(logFC:-0.32,q-value=1.85x10-34)、第 3 年(logFC:-0.28,q-value=6.95x10-29)、第 4 年(logFC:-0.30,q-value=4.13x10-28)和第 5 年(logFC:-0.30,q-value=2.78x10-26)。结论这些分析表明,血浆中的 PEDF 在 MBS 后会持续减少,而这种蛋白质与患有 T2D 的青少年出现严重白蛋白尿和高血压的风险密切相关。PEDF 与血管生成和内皮修复机制受损导致的内皮功能障碍和血管损伤有关。披露 P. Narongkiatikhun:无。Y. Choi:无。N. Nguyen:无:无。K. Nash:无。K.L. Tommerdahl:无。M. Kretzler:研究资助;勃林格殷格翰、Certa、Traveere 制药公司、Maze Therapeutics、罗氏制药、阿斯利康、诺和诺德、Moderna 公司、Chinook Therapeutics 公司、angion、礼来糖尿病、Renalytix、吉利德科学公司、Regeneron 制药公司、杨森制药公司。T. Inge:顾问;美敦力、礼来公司、Brainstorm Therapeutics。股票/股东;Standard Bariatrics。顾问;Teleflex。J.R. Ryder:无。L. Pyle:无:无。P. Bjornstad:顾问;阿斯利康、勃林格殷格翰。顾问团;礼来糖尿病、诺和诺德、拜耳公司、Horizon Therapeutics plc。资助国立卫生研究院
{"title":"1135-P: Pigment Epithelium–Derived Factor, Diabetic Kidney Disease, and Hypertension—Deciphering the Proteomic Response to Metabolic Bariatric Surgery in Adolescents","authors":"PHOOM NARONGKIATIKHUN, YE JI CHOI, NHUNG NGUYEN, KELLY NASH, KALIE L. TOMMERDAHL, MATTHIAS KRETZLER, THOMAS INGE, JUSTIN R. RYDER, LAURA PYLE, PETTER BJORNSTAD","doi":"10.2337/db24-1135-p","DOIUrl":"https://doi.org/10.2337/db24-1135-p","url":null,"abstract":"Introduction & Objective: This study aims to explore the effects of metabolic bariatric surgery (MBS) on plasma proteins linked to diabetic kidney disease and hypertension in youth with type 2 diabetes (T2D). Methods: We measured 7604 proteins in 326 plasma samples from severely obese youth, both with and without T2D, in the Teen-LABS study, examining pre- and post-MBS changes (6 month, 1, 2-, 3-, 4-, and 5-year follow-up). This analysis focused on proteins identified in the TODAY cohort as predictors of severe albuminuria (ACR ≥300 mg/g) and hypertension (SBP≥130/80 mm Hg), in youth with T2D (n=374), using Cox proportional hazard models adjusted for age, sex, HbA1c, log-transformed triglycerides and estimated insulin sensitivity. A mixed model evaluated proteomic changes post-MBS, maintaining a 5% false discovery rate with reported q-values. Results: In Teen-LABS, several proteins associated with a higher risk of severe albuminuria and hypertension in TODAY showed notable post-surgical downregulation. Higher pigment epithelium-derived factor (PEDF) at baseline predicted onset to severe albuminuria (HR: 1.63, 95% CI 1.12, 2.37, per 1 SD increment) and hypertension (HR: 1.41, 95% CI 1.22, 1.63, per 1 SD increment) over 15 years in TODAY after multivariable adjustments. In Teen-LABS, PEDF decreased post-MBS compared to baseline at 6 months follow-up (logFC: -0.30, q-value=1.24x10-31), year 1 (logFC: -0.28, q-value=2.35x10-29), year 2 (logFC: -0.32, q-value=1.85x10-34), year 3 (logFC: -0.28, q-value=6.95x10-29), year 4 (logFC: -0.30, q-value=4.13x10-28) and year 5 (logFC: -0.30, q-value=2.78x10-26). Conclusion: These analyses show durable attenuation of plasma PEDF after MBS, a protein strongly associated with risk of severe albuminuria and hypertension in youth with T2D. PEDF is implicated in endothelial dysfunction and vascular damage through impaired angiogenesis and endothelial repair mechanisms. Disclosure P. Narongkiatikhun: None. Y. Choi: None. N. Nguyen: None. K. Nash: None. K.L. Tommerdahl: None. M. Kretzler: Research Support; Boehringer-Ingelheim, Certa, Traveere Pharmaceuticals, Maze Therapeutics, Roche Pharmaceuticals, AstraZeneca, Novo Nordisk, Moderna, Inc., Chinook Therapeutics Inc., angion, Lilly Diabetes, Renalytix, Gilead Sciences, Inc., Regeneron Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc. T. Inge: Consultant; Medtronic, Eli Lilly and Company, Brainstorm Therapeutics. Stock/Shareholder; Standard Bariatrics. Consultant; Teleflex. J.R. Ryder: None. L. Pyle: None. P. Bjornstad: Consultant; AstraZeneca, Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes, Novo Nordisk, Bayer Inc., Horizon Therapeutics plc. Funding National Institutes of Health","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730485","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}
引用次数: 0
1004-P: Remote Initiation of Continuous Glucose Monitoring in Older Adults Using Insulin 1004-P: 对使用胰岛素的老年人进行远程连续血糖监测
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-1004-p
CATHERINE MAHONEY, CHRISTINE SLYNE, MEDHA MUNSHI, COLIN D. CONERY, HALEY BRABANT, NOA KRAKOFF, JANE D. BULGER, RUTH S. WEINSTOCK, ELENA TOSCHI
Background & Objective: Initiation of continuous glucose monitoring (CGM) remotely in adults with diabetes (DM) has been shown beneficial. However, this model has not been evaluated in older adults. The objective of this study was to assess the benefit and challenges encountered by older patients on multiple daily insulin injections (MDI) initiating CGM using a virtual platform. Methods: Older adults with DM who are participating in an ongoing study on initiation CGM remotely between January-December 2023 were interviewed. Interviews were transcribed, de-identified, coded, and qualitatively analyzed. Baseline demographic characteristics were collected. Results: Interim analysis of 24 interviews was conducted: age 72 ± 4 years, duration of diabetes 30 ± 15 years, 52% female, 76% white, 52% having type 1 diabetes (T1DM), 72% CGM naïve, HbA1C 8.1 ± 1.6, 92% on MDI, and 84% utilizing Medicare as primary insurance. Overarching themes were the use of remote education, initiation of CGM remotely, and ongoing use of CGM. All 100% surveyed participants favorably rated the remote education and its ease of scheduling as well as the overall value of CGM. All participants were able to initiate and maintained CGM use successfully with remote education assistance, with 95% of participants planning to continue to use CGM after study completion. The challenges reported with the CGM use included difficulty with mobile application (33%), annoyance with alarms (50%), and concerns for Medicare coverage (42%). Conclusions: The results of this qualitative analysis show that in our cohort, remote initiation of CGM in older adults was perceived positively, despite some challenges. Disclosure C. Mahoney: None. C. Slyne: None. M. Munshi: Consultant; Sanofi. C.D. Conery: None. H. Brabant: None. N. Krakoff: None. J.D. Bulger: None. R.S. Weinstock: Research Support; Eli Lilly and Company, Tandem Diabetes Care, Inc., Diasome, Amgen Inc., MannKind Corporation, Insulet Corporation, Novo Nordisk. Other Relationship; Dexcom, Inc. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sanofi. Funding The Leona M. and Harry B. Helmsley Charitable Trust
背景 & 目的:对成人糖尿病患者进行远程连续血糖监测(CGM)已被证明是有益的。然而,这种模式尚未在老年人中进行评估。本研究旨在评估每日多次胰岛素注射(MDI)的老年患者使用虚拟平台启动 CGM 的益处和遇到的挑战。方法:对 2023 年 1 月至 12 月期间参与正在进行的远程启动 CGM 研究的 DM 老年患者进行访谈。对访谈内容进行转录、去标识、编码和定性分析。同时还收集了基线人口特征。结果对 24 个访谈进行了中期分析:年龄 72 ± 4 岁,糖尿病病程 30 ± 15 年,52% 女性,76% 白人,52% 患有 1 型糖尿病 (T1DM),72% 未使用 CGM,HbA1C 8.1 ± 1.6,92% 使用 MDI,84% 使用医疗保险作为主要保险。首要主题是使用远程教育、远程启动 CGM 和持续使用 CGM。所有接受调查的 100% 参与者都对远程教育及其时间安排的便捷性以及 CGM 的整体价值给予了好评。所有参与者都能在远程教育的帮助下成功启动并坚持使用 CGM,95% 的参与者计划在研究完成后继续使用 CGM。据报告,使用 CGM 所面临的挑战包括手机应用困难(33%)、警报烦人(50%)以及对医疗保险覆盖范围的担忧(42%)。结论:这项定性分析的结果表明,在我们的队列中,尽管存在一些挑战,但老年人对远程启动 CGM 的看法是积极的。披露 C. Mahoney:无。C. Slyne:无。M. Munshi:赛诺菲顾问。C.D. Conery:无:无。H. Brabant:无。N. Krakoff:无。J.D. Bulger:无。R.S. Weinstock:研究支持;礼来公司、Tandem 糖尿病护理公司、Diasome、安进公司、MannKind 公司、Insulet 公司、诺和诺德公司。其他关系;Dexcom,Inc.E. Toschi:顾问;Vertex 制药公司、赛诺菲。资金来源 Leona M. and Harry B. Helmsley 慈善信托基金
{"title":"1004-P: Remote Initiation of Continuous Glucose Monitoring in Older Adults Using Insulin","authors":"CATHERINE MAHONEY, CHRISTINE SLYNE, MEDHA MUNSHI, COLIN D. CONERY, HALEY BRABANT, NOA KRAKOFF, JANE D. BULGER, RUTH S. WEINSTOCK, ELENA TOSCHI","doi":"10.2337/db24-1004-p","DOIUrl":"https://doi.org/10.2337/db24-1004-p","url":null,"abstract":"Background & Objective: Initiation of continuous glucose monitoring (CGM) remotely in adults with diabetes (DM) has been shown beneficial. However, this model has not been evaluated in older adults. The objective of this study was to assess the benefit and challenges encountered by older patients on multiple daily insulin injections (MDI) initiating CGM using a virtual platform. Methods: Older adults with DM who are participating in an ongoing study on initiation CGM remotely between January-December 2023 were interviewed. Interviews were transcribed, de-identified, coded, and qualitatively analyzed. Baseline demographic characteristics were collected. Results: Interim analysis of 24 interviews was conducted: age 72 ± 4 years, duration of diabetes 30 ± 15 years, 52% female, 76% white, 52% having type 1 diabetes (T1DM), 72% CGM naïve, HbA1C 8.1 ± 1.6, 92% on MDI, and 84% utilizing Medicare as primary insurance. Overarching themes were the use of remote education, initiation of CGM remotely, and ongoing use of CGM. All 100% surveyed participants favorably rated the remote education and its ease of scheduling as well as the overall value of CGM. All participants were able to initiate and maintained CGM use successfully with remote education assistance, with 95% of participants planning to continue to use CGM after study completion. The challenges reported with the CGM use included difficulty with mobile application (33%), annoyance with alarms (50%), and concerns for Medicare coverage (42%). Conclusions: The results of this qualitative analysis show that in our cohort, remote initiation of CGM in older adults was perceived positively, despite some challenges. Disclosure C. Mahoney: None. C. Slyne: None. M. Munshi: Consultant; Sanofi. C.D. Conery: None. H. Brabant: None. N. Krakoff: None. J.D. Bulger: None. R.S. Weinstock: Research Support; Eli Lilly and Company, Tandem Diabetes Care, Inc., Diasome, Amgen Inc., MannKind Corporation, Insulet Corporation, Novo Nordisk. Other Relationship; Dexcom, Inc. E. Toschi: Consultant; Vertex Pharmaceuticals Incorporated, Sanofi. Funding The Leona M. and Harry B. Helmsley Charitable Trust","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730543","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}
引用次数: 0
104-OR: State-Dependent Activity in Hindbrain Glucagon-Like Peptide 1—Producing Neurons Regulates Consummatory and Valence Behavior through Functionally Interconnected Hypothalamic and Limbic Circuits 104-OR: 后脑胰高血糖素样肽 1(Glucagon-Like Peptide 1)产生神经元的状态依赖性活动通过功能上相互关联的下丘脑和边缘环路调控消费行为和价值行为
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-104-or
MIGUEL DURAN, SONJA VIRKUS, KYLIE A. MCMICHEN, YASLLE ANDRADE CAVALCANTE MORAES, ESHITA YADAV, JAGJOT K. SINGH, ZOE FOKAKIS, SAMANTHA Q. STOCKING, SAMUEL O. POOLE, CHAD S. HUNTER, KIRK M. HABEGGER, JAMES A. HARDAWAY
Introduction: Glucagon-like peptide 1 (GLP-1) therapeutics have experienced a meteoric rise in adoption, but our understanding of the endogenous systems that produce GLP-1 and how they regulate behavior remain incomplete. Preproglucagon neurons in the nucleus of the solitary tract (GcgNTS neurons) are the primary source of GLP-1 in the brain. In this study, we examined the neurophysiological and causal contributions of GcgNTS neurons to consummatory and valence behavior. Methods: electrophysiology, in vivo optogenetics, fiber photometry. Results: Using electrophysiology, we observed that GcgNTS neuron neural firing and excitability is reduced in response to 24-hour food deprivation that varied by sex. Conversely, GcgNTS neurons significantly increase their firing rate after a brief 1-hour chow refeed after food deprivation. Consistent with this, GcgNTS neurons display elevated Fos levels following binge-like consumption of palatable high-fat diet. Using in vivo optogenetics, we observed that optogenetic activation of GcgNTS neurons produced anxiety and negative valence that varied by sex. High-frequency activation of GcgNTS neurons also reduced feeding and appetitive behavior. Interestingly, high-frequency activation of GcgNTS neurons produced lasting effects that persisted after cessation of laser illumination. Using a novel transgenic mouse, Gcg-IRES-FlpO, crossed to Glp1r-Cre mice combined with viral and transgenic reporters, we found that GcgNTS neurons and Glp1r neurons in the hypothalamus and amygdala make reciprocal connections. Currently, we are measuring functional connections between GcgNTS neurons and Glp1r neurons in the paraventricular nucleus of the hypothalamus and amygdala. Conclusions: GcgNTS neurons control valence and consumption, interacting with an interconnected GLP-1R-expressing network in the hypothalamus and amygdala. Disclosure M. Duran: None. S. Virkus: None. K.A. McMichen: None. Y. Andrade Cavalcante Moraes: None. E. Yadav: None. J.K. Singh: None. Z. Fokakis: None. S.Q. Stocking: None. S.O. Poole: None. C.S. Hunter: None. K.M. Habegger: Research Support; Eli Lilly and Company. Consultant; Glyscend Inc. Stock/Shareholder; Glyscend Inc. Consultant; Merck & Co., Inc. Research Support; Novo Nordisk. Advisory Panel; Abvance Therapeutics. J.A. Hardaway: None. Funding K01DK115902R03DK129561P30DK079626P30DK056336
简介:胰高血糖素样肽1(GLP-1)治疗药物的应用如雨后春笋般涌现,但我们对产生GLP-1的内源性系统及其如何调节行为的了解仍不全面。孤束核中的前胰高血糖素神经元(GcgNTS 神经元)是大脑中 GLP-1 的主要来源。在这项研究中,我们考察了 GcgNTS 神经元对消耗行为和情绪行为的神经生理学和因果贡献。方法:电生理学、体内光遗传学、纤维光度计。结果通过电生理学研究,我们观察到 GcgNTS 神经元的神经发射和兴奋性在 24 小时食物剥夺后会降低,且因性别而异。相反,GcgNTS神经元在被剥夺食物后短暂进食1小时后,其发射率会显著增加。与此相一致的是,GcgNTS神经元在暴饮暴食般摄入适口的高脂肪饮食后显示出升高的Fos水平。我们使用体内光遗传学方法观察到,光遗传学激活 GcgNTS 神经元会产生焦虑和负性情绪,并因性别而异。高频激活 GcgNTS 神经元也会减少进食和食欲行为。有趣的是,高频激活 GcgNTS 神经元产生的持久效应在停止激光照射后仍然存在。利用一种新型转基因小鼠 Gcg-IRES-FlpO 与 Glp1r-Cre 小鼠杂交,并结合病毒和转基因报告,我们发现 GcgNTS 神经元与下丘脑和杏仁核中的 Glp1r 神经元之间存在相互联系。目前,我们正在测量 GcgNTS 神经元与下丘脑室旁核和杏仁核中 Glp1r 神经元之间的功能连接。结论GcgNTS神经元与下丘脑和杏仁核中相互关联的GLP-1R表达网络相互作用,控制着情绪和消耗。披露 M. Duran:无。S. Virkus: 无。K.A. McMichen:无。Y. Andrade Cavalcante Moraes: None.E. Yadav:无。J.K. Singh:无。Z. Fokakis:Z. Fokakis: None.S.Q. Stocking:无。S.O. Poole:无。C.S. Hunter:无。K.M. Habegger:研究支持;礼来公司。顾问;Glyscend Inc.股票/股东;Glyscend Inc.顾问;Merck & Co.研究支持;诺和诺德顾问团; Abvance Therapeutics.J.A. Hardaway:无。Funding K01DK115902R03DK129561P30DK079626P30DK056336
{"title":"104-OR: State-Dependent Activity in Hindbrain Glucagon-Like Peptide 1—Producing Neurons Regulates Consummatory and Valence Behavior through Functionally Interconnected Hypothalamic and Limbic Circuits","authors":"MIGUEL DURAN, SONJA VIRKUS, KYLIE A. MCMICHEN, YASLLE ANDRADE CAVALCANTE MORAES, ESHITA YADAV, JAGJOT K. SINGH, ZOE FOKAKIS, SAMANTHA Q. STOCKING, SAMUEL O. POOLE, CHAD S. HUNTER, KIRK M. HABEGGER, JAMES A. HARDAWAY","doi":"10.2337/db24-104-or","DOIUrl":"https://doi.org/10.2337/db24-104-or","url":null,"abstract":"Introduction: Glucagon-like peptide 1 (GLP-1) therapeutics have experienced a meteoric rise in adoption, but our understanding of the endogenous systems that produce GLP-1 and how they regulate behavior remain incomplete. Preproglucagon neurons in the nucleus of the solitary tract (GcgNTS neurons) are the primary source of GLP-1 in the brain. In this study, we examined the neurophysiological and causal contributions of GcgNTS neurons to consummatory and valence behavior. Methods: electrophysiology, in vivo optogenetics, fiber photometry. Results: Using electrophysiology, we observed that GcgNTS neuron neural firing and excitability is reduced in response to 24-hour food deprivation that varied by sex. Conversely, GcgNTS neurons significantly increase their firing rate after a brief 1-hour chow refeed after food deprivation. Consistent with this, GcgNTS neurons display elevated Fos levels following binge-like consumption of palatable high-fat diet. Using in vivo optogenetics, we observed that optogenetic activation of GcgNTS neurons produced anxiety and negative valence that varied by sex. High-frequency activation of GcgNTS neurons also reduced feeding and appetitive behavior. Interestingly, high-frequency activation of GcgNTS neurons produced lasting effects that persisted after cessation of laser illumination. Using a novel transgenic mouse, Gcg-IRES-FlpO, crossed to Glp1r-Cre mice combined with viral and transgenic reporters, we found that GcgNTS neurons and Glp1r neurons in the hypothalamus and amygdala make reciprocal connections. Currently, we are measuring functional connections between GcgNTS neurons and Glp1r neurons in the paraventricular nucleus of the hypothalamus and amygdala. Conclusions: GcgNTS neurons control valence and consumption, interacting with an interconnected GLP-1R-expressing network in the hypothalamus and amygdala. Disclosure M. Duran: None. S. Virkus: None. K.A. McMichen: None. Y. Andrade Cavalcante Moraes: None. E. Yadav: None. J.K. Singh: None. Z. Fokakis: None. S.Q. Stocking: None. S.O. Poole: None. C.S. Hunter: None. K.M. Habegger: Research Support; Eli Lilly and Company. Consultant; Glyscend Inc. Stock/Shareholder; Glyscend Inc. Consultant; Merck & Co., Inc. Research Support; Novo Nordisk. Advisory Panel; Abvance Therapeutics. J.A. Hardaway: None. Funding K01DK115902R03DK129561P30DK079626P30DK056336","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730550","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}
引用次数: 0
1552-P: Mutations with Residual CFTR Function Are Associated to Better Glucose Tolerance and Insulin Secretion in Patients with Cystic Fibrosis 1552-P:具有残余 CFTR 功能的突变与囊性纤维化患者更好的葡萄糖耐受性和胰岛素分泌有关
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-1552-p
ANDREA FOPPIANI, FABIANA CICIRIELLO, FEDERICO ALGHISI, VINCENZINA LUCIDI, FEDERICA SILEO, MARIA CRISTINA LUCANTO, FABIOLA CORTI, CARLA COLOMBO, ALBERTO BATTEZZATI
People with Cystic Fibrosis (pwCF) exhibit a defect of insulin secretion[1], potentially leading to Cystic Fibrosis Related Diabetes. Little information exists about the molecular mechanism that links the defect of insulin secretion to the CF-causing variants of the CFTR gene[2,3]. We sought to describe the relationship between the CFTR function and β-cell function in pwCF. We studied 341 patients (193 (57%) females, 271 (79%) pancreatic insufficient, median (IQR) age 19 (15, 24) years) with the oral glucose tolerance test (OGTT), sampling glucose, insulin, and C-peptide before and every 30 minutes over the 2 hour OGTT, modeling β-cell function expressed by the β-cell glucose sensitivity[4]. Each patient was characterized by either having at least one allele with a residual function mutation (group 1, 85 (25%)), or a minimal function mutation on both alleles (group 2, 255 (75%) ). After adjusting for sex, pancreatic insufficiency (PI), and age, patients in group 1 displayed better glucose tolerance at all OGTT timepoint (all p=<0.05), and better β-cell glucose sensitivity (22 pmol×min⁻¹×m⁻²×mM⁻¹; 95% CI 9.6, 34; p=<0.001).Within the whole sample, 162 patients (82 (51%) females, 136 (84%) of group 2, 139 (86%) pancreatic insufficient, median (IQR) age 20 (15, 25) years) carried variants on both alleles that had been tested for chloride conductance in the Fischer Rat Thyroid cell line (http://cftr2.org). The mean chloride conductance of the most functional allele was positively related to β-cell glucose sensitivity (0.96; 95% CI 0.13, 1.8; p=0.025), with no PI interaction (interaction term -0.63; 95% CI -3.7, 2.4; p=0.7), and adjusting for differences in sex and age. In conclusion, we have shown that CFTR function is quantitatively related to β-cell function in pwCF. Even though exocrine PI is associated with worse β-cell function, the association of CFTR residual function and β-cell glucose sensitivity is not necessarily mediated by exocrine PI. Disclosure A. Foppiani: None. F. Ciciriello: None. F. Alghisi: None. V. Lucidi: None. F. Sileo: None. M. Lucanto: None. F. Corti: None. C. Colombo: None. A. Battezzati: None. Funding Cystic Fibrosis Research Foundation FFC#16/2005, FFC#21/2013, FFC#20/2016, and FFC#24/2019
囊性纤维化患者(pwCF)表现出胰岛素分泌缺陷[1],可能导致囊性纤维化相关糖尿病。关于胰岛素分泌缺陷与 CFTR 基因致病变体之间的分子机制[2,3],目前几乎没有任何信息。我们试图描述 CFTR 功能与 pwCF 中 β 细胞功能之间的关系。我们对 341 名患者(193 名(57%)女性,271 名(79%)胰腺功能不全,中位数(IQR)年龄 19(15,24)岁)进行了口服葡萄糖耐量试验(OGTT),在 2 小时 OGTT 之前和 2 小时 OGTT 期间每隔 30 分钟采集葡萄糖、胰岛素和 C 肽的样本,通过 β 细胞葡萄糖敏感性来模拟 β 细胞功能[4]。每位患者的特征是至少有一个等位基因存在残余功能突变(第 1 组,85 例(25%)),或两个等位基因都存在最小功能突变(第 2 组,255 例(75%))。在对性别、胰腺功能不全(PI)和年龄进行调整后,第1组患者在所有OGTT时间点的葡萄糖耐量均较好(所有p=<0.05),β细胞葡萄糖敏感性较好(22 pmol×min-¹×m-²×m-¹; 95% CI 9.6, 34; p=<0.001)。在整个样本中,162 名患者(82 名(51%)女性,136 名(84%)第 2 组患者,139 名(86%)胰腺功能不全患者,中位(IQR)年龄为 20(15,25)岁)的两个等位基因上都携带变体,这些变体已在费舍尔大鼠甲状腺细胞系(http://cftr2.org)中进行了氯传导测试。功能最强等位基因的平均氯离子传导率与β细胞葡萄糖敏感性呈正相关(0.96;95% CI 0.13,1.8;p=0.025),无PI交互作用(交互作用项-0.63;95% CI -3.7,2.4;p=0.7),并调整了性别和年龄差异。总之,我们已经证明,CFTR 功能与 pwCF 中的β细胞功能有定量关系。尽管外分泌 PI 与较差的 β 细胞功能有关,但 CFTR 残余功能与 β 细胞葡萄糖敏感性之间的关联并不一定是由外分泌 PI 介导的。披露 A. Foppiani:无。F. Ciciriello: 无。F. Alghisi:无。V. Lucidi:无。F. Sileo:无:无。M. Lucanto:无。F. Corti:无。C. Colombo:无。A. Battezzati:无。资助 囊性纤维化研究基金会 FFC#16/2005、FFC#21/2013、FFC#20/2016 和 FFC#24/2019
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引用次数: 0
1927-LB: Impact of Continuous Glucose Monitoring Use on Hospitalizations in People with Type 2 Diabetes—Real-World Analysis 1927-LB: 连续血糖监测的使用对 2 型糖尿病患者住院治疗的影响--真实世界分析
IF 7.7 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-19 DOI: 10.2337/db24-1927-lb
SATISH K. GARG, IRL B. HIRSCH, ENRICO REPETTO, JANET K. SNELL-BERGEON, BRIAN ULMER, CHRISTOPHER PERKINS, RICHARD M. BERGENSTAL
Introduction & Objective: The increasing prevalence of diabetes in the US continues to drive a steady rise in healthcare resource utilization. The real-world impact of continuous glucose monitoring (CGM) on hospitalizations in a broad type 2 diabetes population is not completely understood. Methods: In this retrospective analysis, we used Optum's de-identified Market Clarity data of >79 million people to evaluate CGM use in 74,264 people with type 2 diabetes who were treated with non-insulin (NIT; n=25,788), basal insulin (BIT; n=25,292), and prandial insulin therapy (PIT; n=23,184). The primary outcomes were changes in all-cause hospitalizations (ACH), acute diabetes-related hospitalizations (ADH), and acute diabetes-related emergency room visits (ADER) during the 6- and 12-months post-index period. Results: ACH, ADH, and ADER were significantly reduced in the first 6 months (post-index) in all three groups: NIT (14%, 32%, 30%), BIT (25%, 57%, 37%), PIT (25%, 54%, 36%) respectively. (Figure 1) The reductions were sustained during 6-12 months in NIT (10%, 31%, 30%), BIT (23%, 56%, 34%), and PIT (19%, 49%, 36%) respectively (all p<0.0001). Conclusion: The use of CGM in real-world across different therapeutic regimes in people with type 2 diabetes was associated with significant reductions in all-cause hospitalizations, acute diabetes-related hospitalizations and ER visits. Disclosure S.K. Garg: Research Support; Eli Lilly and Company. Advisory Panel; Medtronic. Research Support; Medtronic. Advisory Panel; Novo Nordisk. Research Support; DarioHealth Corp., Dexcom, Inc., Diasome. Advisory Panel; Roche Diabetes Care. I.B. Hirsch: Advisory Panel; Abbott. Research Support; Dexcom, Inc. Advisory Panel; Roche Diabetes Care. Research Support; MannKind Corporation, Tandem Diabetes Care, Inc. Advisory Panel; embecta. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Vertex Pharmaceuticals Incorporated. E. Repetto: Employee; Roche Diabetes Care. J.K. Snell-Bergeon: None. B. Ulmer: Employee; Roche Diabetes Care. C. Perkins: Employee; Roche Diabetes Care. R.M. Bergenstal: Other Relationship; Abbott. Research Support; Arkray Marketing. Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur. Other Relationship; Dexcom, Inc., Eli Lilly and Company. Consultant; embecta, Hygieia. Research Support; Insulet Corporation. Consultant; MannKind Corporation. Other Relationship; Medtronic, Novo Nordisk. Consultant; Onduo LLC, Roche Diabetes Care. Other Relationship; Sanofi. Research Support; Tandem Diabetes Care, Inc. Other Relationship; UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. Funding Roche Diagnostics, Diabetes Care
导言与目标:美国糖尿病患病率不断上升,导致医疗资源利用率持续上升。连续血糖监测(CGM)对广大 2 型糖尿病患者住院治疗的实际影响尚不完全清楚。方法:在这项回顾性分析中,我们使用 Optum 的去标识化 Market Clarity 数据,对 74,264 名接受非胰岛素 (NIT;人数=25,788)、基础胰岛素 (BIT;人数=25,292) 和餐前胰岛素治疗 (PIT;人数=23,184) 的 2 型糖尿病患者使用 CGM 的情况进行了评估。主要结果是在指数期后的 6 个月和 12 个月期间,全因住院率 (ACH)、急性糖尿病相关住院率 (ADH) 和急性糖尿病相关急诊就诊率 (ADER) 的变化。结果:在指数发布后的前 6 个月中(指数发布后),所有三组的 ACH、ADH 和 ADER 均明显减少:NIT(分别为 14%、32%、30%)、BIT(分别为 25%、57%、37%)、PIT(分别为 25%、54%、36%)。(图 1)NIT 组(10%、31%、30%)、BIT 组(23%、56%、34%)和 PIT 组(19%、49%、36%)的降幅在 6-12 个月内保持不变(所有 p<0.0001)。结论在不同治疗方案的真实世界中,2 型糖尿病患者使用 CGM 可显著降低全因住院率、糖尿病相关急性住院率和急诊就诊率。披露 S.K. Garg:研究支持;礼来公司。顾问团;美敦力。研究支持;美敦力。顾问团;诺和诺德公司。研究支持;DarioHealth Corp.顾问小组;罗氏糖尿病护理公司。I.B. Hirsch:顾问团;雅培。研究支持;Dexcom, Inc.顾问小组;罗氏糖尿病护理公司。研究支持;MannKind Corporation、Tandem Diabetes Care, Inc.顾问团;embecta.研究支持;Tandem Diabetes Care, Inc.顾问团;Vertex Pharmaceuticals Incorporated。E. Repetto:罗氏糖尿病护理公司雇员。J.K. Snell-Bergeon:无。B. Ulmer:罗氏糖尿病护理公司员工。C. Perkins:罗氏糖尿病护理公司员工。R.M. Bergenstal:其他关系;雅培。研究支持;Arkray Marketing。顾问;Ascensia Diabetes Care、Bigfoot Biomedical, Inc.、CeQur。其他关系;Dexcom 公司、礼来公司。顾问;embecta、Hygieia。研究支持;Insulet 公司。顾问;MannKind 公司。其他关系;美敦力、诺和诺德。顾问;Onduo LLC、罗氏糖尿病护理公司。其他关系;赛诺菲。研究支持;Tandem Diabetes Care, Inc.其他关系;联合健康集团。顾问;Vertex Pharmaceuticals Incorporated、Zealand Pharma A/S。资助罗氏诊断公司、糖尿病护理公司。
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Diabetes
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