Diabetic kidney disease

糖尿病肾病
  • 文章类型: Journal Article
    Finerenone已被批准用于治疗糖尿病肾病(DKD),降低心肾风险。目前缺乏用于DKD管理的finenone治疗的实际数据。本研究旨在首次在现实医学环境中探讨菲雷酮对中国DKD人群肾脏参数的影响。特别是与肾素-血管紧张素系统抑制剂(RASi)和钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)联合使用。
    选择42例DKD患者并完成6个月的finenerone治疗。每次就诊时收集肾脏参数和不良反应。
    尿白蛋白与肌酐比值中位数(UACR)为1426.11(755.42,3638.23)mg/g。其中,UACR为300-5000mg/g的患者比例为76.2%,UACR>5000mg/g的患者比例为14.3%。估计肾小球滤过率(eGFR)的中位数为54.50(34.16,81.73)mL/min/1.73m2。Finenerone在整个研究期间显着降低UACR(p<0.05)。在第6个月,UACR的最大下降为73%。此外,在第6个月,UACR降低30%或更多的患者比例为68.42%.开始使用finenerone后,eGFR的下降幅度较小(9-11%)(p>.05)。由于高钾血症(2.4%)和急性肾损伤(2.4%),每位患者均停用了finetenone。没有病人报告低血压,乳房疼痛,和男性乳房发育症。
    这项来自中国的研究首次表明,在现实世界的DKD治疗中,finerenone降低了UACR,具有可控的安全性。RASi的三联疗法,SGLT2i,在晚期DKD患者中,对于降低白蛋白尿和降低高钾血症风险可能是一种有前景的治疗策略.
    UNASSIGNED: Finerenone has been approved for treating diabetic kidney disease (DKD) with reducing cardiorenal risk. Real-world data on finerenone treatment for the management of DKD are presently lacking. This study aimed to investigate the effect of finerenone on the renal parameters of the Chinese DKD population in the real-world medical setting for the first time, especially in combination with renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i).
    UNASSIGNED: Forty-two DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters and adverse effects were collected at every visit.
    UNASSIGNED: The median urine albumin-to-creatinine ratio (UACR) was 1426.11 (755.42, 3638.23) mg/g. Among them, the proportion of patients with a UACR of 300-5000 mg/g was 76.2%, and the proportion of patients with a UACR of >5000 mg/g was 14.3%. The median estimated glomerular filtration rate (eGFR) was 54.50 (34.16, 81.73) mL/min/1.73 m2. Finerenone decreased the UACR significantly throughout the study period (p < .05). The maximal decline of UACR at month 6 was 73%. Moreover, the proportion of patients with a 30% or greater reduction in UACR was 68.42% in month 6. There was a smaller decline (9-11%) in the eGFR after initiating finerenone (p > .05). One patient each discontinued finerenone due to hyperkalemia (2.4%) and acute kidney injury (2.4%). No patient reported hypotension, breast pain, and gynecomastia.
    UNASSIGNED: This study from China first demonstrated finerenone decreased UACR with manageable safety in real-world DKD treatment. A triple regimen of RASi, SGLT2i, and finerenone may be a promising treatment strategy for lowering albuminuria and reducing hyperkalemia risk in advanced DKD patients.
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  • 文章类型: Journal Article
    在美国,糖尿病肾病(DKD)影响约三分之一的2型糖尿病患者,对医疗保健系统造成重大经济负担,并影响患者的生活质量。
    本研究的目的是量化DKD不同阶段患者的护理负担,并监测这些阶段医疗费用的变化。
    这项研究使用了退伍军人事务国家数据库中的数据,重点关注2016年1月至2022年3月期间诊断为DKD的美国退伍军人。使用描述性统计汇总每月的所有原因的医疗保健费用。我们使用广义线性模型根据阶段计算DKD专利护理的成本,透析阶段,和肾脏替代疗法.
    685,288例DKD患者以男性为主(96.51%),白色(74.42%),非西班牙裔(93.54%)。每位患者每月的平均费用(SD)为1,597美元(3,178美元),$1,772($4,269),$2,857($13,072),3722美元(12134美元),$5,505($14,639),和6,999美元(16,901美元)用于阶段1、2、3a,3b,分别为4和5。接受长期透析的患者的平均每月支出为$12,299。在肾脏替代疗法的第一个月,费用急剧达到峰值,为38,359美元,但随后在1年后下降至6,636美元。
    DKD的经济影响是深远的,强调需要有效的早期检测和疾病管理策略。防止患者发展到DKD晚期阶段将最大程度地减少DKD的经济影响,并将有助于医疗保健系统优化资源分配。
    糖尿病肾病(DKD)给美国的医疗保健系统带来了沉重负担。我们努力缩小疾病负担方面的知识差距,对美国退伍军人进行了DKD患者的护理成本分析.随着阶段进展,每位患者每月的总体护理费用从1,597美元(第1阶段)大幅增加至6,999美元(第5阶段).退伍军人开始接受长期透析后,每月费用超过10,000美元。定量摘要将有助于卫生保健系统在各个疾病部门有效分配资源。
    UNASSIGNED: In the United States, diabetic kidney disease (DKD) affects about one-third of individuals with type 2 diabetes, causing significant economic burdens on the health care system and affecting patients\' quality of life.
    UNASSIGNED: The aim of the study was to quantify the burden of care in patients at different stages of DKD and to monitor shifts in healthcare costs throughout these stages.
    UNASSIGNED: This study used data from the Veterans Affairs National database, focusing on US veterans diagnosed with DKD between January 2016 and March 2022. Aggregated all-cause health care costs per month were summarized using descriptive statistics. We used a generalized linear model to calculate the cost of DKD patent care based on the stages, dialysis phase, and kidney replacement therapy.
    UNASSIGNED: The cohort of 685,288 patients with DKD was predominantly male (96.51%), White (74.42%), and non-Hispanic (93.54%). The mean (SD) per-patient per-month costs were $1,597 ($3,178), $1,772 ($4,269), $2,857 ($13,072), $3,722 ($12,134), $5,505 ($14,639), and $6,999 ($16,901) for stages 1, 2, 3a, 3b, 4 and 5 respectively. The average monthly expenditure for patients receiving long-term dialysis was $12,299. Costs peaked sharply during the first month of kidney replacement therapy at $38,359 but subsequently decreased to $6,636 after 1 year.
    UNASSIGNED: The economic implications of DKD are profound, emphasizing the need for efficient early detection and disease management strategies. Preventing patients from progressing to advanced DKD stage will minimize the economic repercussions of DKD and will assist health care systems in optimizing resource allocation.
    Diabetic kidney disease (DKD) places a substantial burden on health care systems in the United States. In part of our effort to close the knowledge gap around the disease burden, care cost analysis for the patients with DKD was performed for US veterans. Along with stage progression, overall care costs per-patient per-month drastically increases from $1,597 (stage 1) to $6,999 (stage 5). Monthly costs exceeded $10,000 once veterans started to receive long-term dialysis. The quantitative summary will help health care systems efficiently allocate resources across various disease sectors.
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  • 文章类型: Journal Article
    糖尿病中氧化应激和炎症之间的因果关系,连同其相关的肾脏和心血管并发症,已经建立。16种治疗糖尿病肾病的潜在肾脏保护中草药(PRCHMDKD),这是科学的中药(植物药),分为五类(清热,滋阴,祛湿,补气,和协调公式),表现出共同的抗氧化特性,并靶向多种氧化应激途径。然而,时间响应,累积效应,这16种PRCHMDKD对整体和晚期DKD患者心肾和生存结局的安全性(高钾血症风险)仍未解决.
    这项回顾性队列研究分析了2000-2017年的国家健康保险索赔数据。四种统计方法,包括Cox比例风险模型,互补限制平均生存时间(RMST),倾向得分匹配,和终末期肾病(ESRD)的竞争风险分析,被用来调查这种关系。该研究包括43,480名PRCHMDKD用户和在整个DKD患者人群中相同数量的匹配非用户。对于晚期DKD患者,该队列包括1,422名PRCHMDKD用户和同等数量的匹配非用户.
    PRCHMDKD在整体和高级方面的使用,分别,DKD患者与ESRD调整后风险比的时间依赖性降低相关(0.66;95%CI,0.61-0.70vs.0.81;0.65-0.99),全因死亡率(0.48;0.47-0.49vs.0.59;0.50-0.70),和心血管死亡率(0.50;0.48-0.53vs.0.61;0.45-0.82)。在整体和高级中观察到RMST的显着差异,分别,DKD患者,偏爱PRCHMDKD使用:0.31年(95%CI,0.24-0.38)与ESRD为0.61年(0.13-1.10),2.71年(2.60-2.82)vs.全因死亡率为1.50年(1.03-1.98),和1.18年(1.09-1.28)vs.心血管死亡率为0.59年(0.22-0.95)。此外,高钾血症风险没有增加.尽管进行了多种敏感性分析,但这些发现仍然保持一致。值得注意的是,使用16种PRCHMDKD的至少4类或5类和多种植物性药物的累积效应可增强整体和晚期DKD患者的肾脏保护作用.这表明与DKD相关的氧化应激途径中涉及多个靶标。
    这项现实世界研究表明,使用这16种PRCHMDKD可提供时间依赖性的心肾和生存益处,同时确保DKD患者的安全性。
    UNASSIGNED: A causal connection between oxidative stress and inflammation in diabetes, along with its associated renal and cardiovascular complications, has been established. Sixteen prescribed potentially renoprotective Chinese herbal medicines for diabetic kidney disease (PRCHMDKD), which are scientific Chinese medicine (botanical drug) and categorized into five classes (clearing heat, nourishing yin, dampness dispelling, tonifying qi, and harmonizing formulas), exhibit shared antioxidative properties and target multiple oxidative stress pathways. However, the time-response, cumulative effects, and safety (hyperkalemia risk) of these sixteen PRCHMDKD on cardiorenal and survival outcomes in patients with overall and advanced DKD remain unresolved.
    UNASSIGNED: This retrospective cohort study analyzed national health insurance claims data in 2000-2017. Four statistical methods, including Cox proportional hazards models, complementary restricted mean survival time (RMST), propensity score matching, and competing risk analysis for end-stage renal disease (ESRD), were employed to investigate this relationship. The study included 43,480 PRCHMDKD users and an equal number of matched nonusers within the overall DKD patient population. For advanced DKD patients, the cohort comprised 1,422 PRCHMDKD users and an equivalent number of matched nonusers.
    UNASSIGNED: PRCHMDKD use in overall and advanced, respectively, DKD patients was associated with time-dependent reductions in adjusted hazard ratios for ESRD (0.66; 95% CI, 0.61-0.70 vs. 0.81; 0.65-0.99), all-cause mortality (0.48; 0.47-0.49 vs. 0.59; 0.50-0.70), and cardiovascular mortality (0.50; 0.48-0.53 vs. 0.61; 0.45-0.82). Significant differences in RMST were observed in overall and advanced, respectively, DKD patients, favoring PRCHMDKD use: 0.31 years (95% CI, 0.24-0.38) vs. 0.61 years (0.13-1.10) for ESRD, 2.71 years (2.60-2.82) vs. 1.50 years (1.03-1.98) for all-cause mortality, and 1.18 years (1.09-1.28) vs. 0.59 years (0.22-0.95) for cardiovascular mortality. Additionally, hyperkalemia risk did not increase. These findings remained consistent despite multiple sensitivity analyses. Notably, the cumulative effects of utilizing at least four or five classes and multiple botanical drugs from the sixteen PRCHMDKD provided enhanced renoprotection for patients with both overall and advanced DKD. This suggests that there is involvement of multiple targets within the oxidative stress pathways associated with DKD.
    UNASSIGNED: This real-world study suggests that using these sixteen PRCHMDKD provides time-dependent cardiorenal and survival benefits while ensuring safety for DKD patients.
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  • 文章类型: Journal Article
    目的:2型糖尿病(T2DM)和骨代谢紊乱的患病率随年龄增加而增加。糖尿病肾病(DKD)是T2DM最严重的微血管并发症之一,骨代谢紊乱与DKD的发生密切相关。骨转换标志物(BTMs)与老年T2DM患者肾脏疾病之间的关系尚不清楚。因此,本研究旨在调查大样本老年患者中常见BTMs与DKD之间的关联.目的是从骨代谢的角度为早期识别老年T2DM患者中DKD的高危个体提供依据。
    方法:在这项横断面研究中,BTMs是从2,051名住院中国患者的队列中收集的。25-羟基维生素D(25-OH-D),β-交叉圈(β-CTX),骨钙蛋白(OSTEOC),完整的甲状旁腺激素(iPTH),和总I型胶原N端前肽(TP1NP),还有DKD,使用回归分析和限制性三次样条(RCS)曲线分析尿白蛋白-肌酐比值(UACR)和估计肾小球滤过率(eGFR).
    结果:较高的25-OH-D水平与较低的DKD发生率和降低的UACR独立相关。RCS曲线显示25-OH-D与DKD呈线性关系,接近L形。β-CTX与UACR呈独立正相关。OSTEOC与UACR呈独立正相关,与eGFR呈负相关。iPTH与DKD发病率和UACR呈独立正相关,与eGFR呈负相关。此外,RCS曲线显示OSTEOC与iPTH和DKD的非线性关联,接近J形,拐点分别为10.875ng/L和34.15pg/mL。TP1NP与UACR发病率呈独立正相关,与eGFR呈负相关。在RCS模型中,随着TP1NP水平的升高,风险估计值显着增加。
    结论:BTMs与老年T2DM患者肾脏疾病密切相关。这些发现可能有助于临床医生为老年T2DM患者建立更多的预防措施和有针对性的治疗策略。
    OBJECTIVE: The prevalence of type 2 diabetes mellitus (T2DM) and bone metabolism disorders increase with age. Diabetic kidney disease (DKD) is one of the most serious microvascular complications of T2DM, and bone metabolism disorders are closely linked to the occurrence of DKD. The relationship between bone turnover markers(BTMs) and the kidney disease in elderly patients with T2DM remains unclear. Therefore, this study aims to investigate the association between common BTMs and DKD in a large sample of elderly patients. The goal is to provide a basis for early identification of high-risk individuals for DKD among elderly T2DM patients from a bone metabolism perspective.
    METHODS: In this cross-sectional study, BTMs were collected from a cohort of 2,051 hospitalized Chinese patients. The relationships between 25-hydroxyvitamin D (25-OH-D), β-CrossLaps (β-CTX), osteocalcin (OSTEOC), intact parathyroid hormone (iPTH), and total type I collagen N-terminal propeptide (TP1NP), and DKD, as well as urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were analyzed using regression analysis and restrictive cubic spline (RCS) curves.
    RESULTS: Higher 25-OH-D levels were independently linked to a lower incidence of DKD and decreased UACR. The RCS curves showed a linear association of 25-OH-D and DKD, approaching the L-shape. β-CTX was independently and positively correlated with UACR. There is an independent positive correlation between OSTEOC and UACR and a negative correlation with eGFR. iPTH is independently and positively correlated with DKD incidence and UACR, and negatively correlated with eGFR. Additionally, the RCS curves showed a non-linear association of OSTEOC and iPTH and DKD, approaching the J-shape, and the point of inflection is 10.875 ng/L and 34.15 pg/mL respectively. There is an independent positive correlation between TP1NP and UACR incidence, and a negative correlation with eGFR. Risk estimates significantly increase with higher TP1NP levels in the RCS model.
    CONCLUSIONS: BTMs are closely associated with kidney disease in elderly patients with T2DM. These discoveries potentially assist clinicians in establishing more preventive measures and targeted treatment strategies for elderly patients with T2DM.
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  • 文章类型: Journal Article
    目标:在其超过25年的运营范围内,观测,全国范围内,多中心芬兰糖尿病肾病(FinnDiane)研究旨在揭示糖尿病肾病的潜在机制,特别关注其代谢危险因素。我们试图汇编与该主题相关的关键发现,并提供有关1型糖尿病患者糖尿病肾脏疾病自然病程的最新观点。
    方法:在这篇叙述性综述中,FinnDiane研究发表的与该主题相关的文章与其他人发表的作品一起被识别和总结,当相关。
    结果:FinnDiane研究强调了血糖异常和胰岛素抵抗的重要性,内脏脂肪量增加,高血压和血脂异常-尤其是高甘油三酯和残余胆固醇-是糖尿病肾病的危险因素。腹部肥胖等因素似乎会影响疾病的早期阶段,而代谢综合征的存在在后期阶段变得有牵连。流行病学报告显示,在最初的下降之后,蛋白尿的累积发病率在1980年代后趋于稳定,肾功能衰竭的进展率仍然很高。幸运的是,23%的FinnDiane队列回归到蛋白尿的晚期阶段,改善其整体预后。
    结论:与1型糖尿病相关的蛋白尿负担仍然很大,因此,新型肾脏保护疗法备受期待。此外,考虑到代谢因素影响糖尿病肾病早期和晚期的进展,应强调确保达到他们的治疗目标。
    OBJECTIVE: Across its operational span of more than 25 years, the observational, nationwide, multicentre Finnish Diabetic Nephropathy (FinnDiane) Study has aimed to unravel mechanisms underlying diabetic kidney disease, with a special focus on its metabolic risk factors. We sought to compile key findings relating to this topic and to offer a current perspective on the natural course of diabetic kidney disease among individuals with type 1 diabetes.
    METHODS: In this narrative review, articles relevant to the subject published by the FinnDiane Study were identified and summarized together with work published by others, when relevant.
    RESULTS: The FinnDiane Study has underscored the significance of dysglycaemia and insulin resistance, increased visceral fat mass, hypertension and dyslipidaemia-particularly high triglycerides and remnant cholesterol-as risk factors for diabetic kidney disease. Factors like abdominal obesity seem to influence the early stages of the disease, while the presence of the metabolic syndrome becomes implicated at later stages. Epidemiological reports have revealed that after an initial decline, the cumulative incidence of albuminuria plateaued post-1980s, with the progression rate to kidney failure remaining high. Fortunately, 23% of the FinnDiane cohort regressed to less advanced stages of albuminuria, improving their overall prognosis.
    CONCLUSIONS: A substantial burden of albuminuria associated with type 1 diabetes persists, and therefore, novel kidney-protecting therapies are highly awaited. In addition, given that metabolic factors influence the progression of diabetic kidney disease both in its early and advanced stages, emphasis should be placed on ensuring that their treatment targets are met.
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  • 文章类型: Journal Article
    冠状病毒病2019(COVID-19)对中国糖尿病肾病(DKD)患者的影响尚未完全了解。本研究旨在调查肾活检后DKD队列中的感染状况,并分析疫苗接种和感染率。以及症状严重程度,DKD患者的各种肾脏病变。
    这项流行病学调查,以COVID-19为中心,采用了中国DKD和肾穿刺随访队列。定制的问卷可以实现标准化的数据收集。它收集了有关临床特征的数据,疫苗接种和感染状况,和不同的病理类型。该研究分析了各种病理类型的疫苗接种与感染状态之间的关系,评估感染患者的特征和治疗结果。
    总共,对来自中国26个省的437例DKD患者进行了中位随访,中位随访时间为44.6±20个月。COVID-19感染,疫苗接种,新型冠状病毒肺炎(NCP)发病率为73.68%,59.3%,和6.63%,分别。10例NCP患者患有严重肺炎或死于COVID-19。肾脏病理显示167例(38.22%)患者患有糖尿病肾病(DN),171(39.13%)患有非糖尿病肾病(NDRD),99例患有DN和NDRD(22.65%)。DN组的接种率最低(54.5%),全因死亡率最高(3.6%),和最高终点率(34.10%)。与感染前未接种疫苗的患者(117例)相比,接种疫苗的患者(198例)NCP降低(6.6%vs.13.7%),严重程度(1.0%与3.4%),和终点(9.10%与31.60%)率。
    疫苗接种可以预防感染并减轻DKD患者的COVID-19严重程度;因此,提高疫苗接种率尤为重要。
    ClinicalTrails.gov,NCT05888909。
    UNASSIGNED: The impact of coronavirus disease 2019 (COVID-19) on diabetic kidney disease (DKD) patients in China is not fully understood. This study aimed to investigate infection status in a DKD cohort post-renal biopsy and analyze vaccination and infection rates, as well as symptom severity, across various renal pathologies in DKD patients.
    UNASSIGNED: This epidemiological survey, centered on COVID-19, employed a Chinese DKD and renal puncture follow-up cohort. A customized questionnaire enabled standardized data gathering. It collected data on clinical characteristics, vaccination and infection statuses, and diverse pathological types. The study analyzed the relationship between vaccination and infection statuses across various pathological types, evaluating characteristics and treatment outcomes in patients with infections.
    UNASSIGNED: In total, 437 patients with DKD from 26 Chinese provinces were followed up for a median of 44.6 ± 20 months. COVID-19 infection, vaccination, and novel coronavirus pneumonia (NCP) rates were 73.68%, 59.3%, and 6.63%, respectively. Ten patients with NCP had severe pneumonia or died of COVID-19. Renal pathology revealed that 167 (38.22%) patients had diabetic nephropathy (DN), 171 (39.13%) had non-diabetic renal disease (NDRD), and 99 had DN and NDRD (22.65%). The DN group had the lowest vaccination (54.5%), highest all-cause mortality (3.6%), and highest endpoint rates (34.10%). Compared to patients who were not vaccinated pre-infection (117 cases), vaccinated patients (198 cases) had reduced NCP (6.6% vs. 13.7%), severity (1.0% vs. 3.4%), and endpoint (9.10% vs. 31.60%) rates.
    UNASSIGNED: Vaccination can prevent infection and diminish COVID-19 severity in patients with DKD; therefore, increasing vaccination rates is particularly important.
    UNASSIGNED: ClinicalTrails.gov, NCT05888909.
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  • 文章类型: Journal Article
    Cotadutide是一种胰高血糖素样肽-1(GLP-1)和胰高血糖素受体激动剂,可改善2型糖尿病(T2D)和慢性肾脏疾病(CKD)患者的肾功能。在这个2b阶段的研究中,T2D和CKD患者,估计的肾小球滤过率[eGFR]为20或更高且低于90mL/min/1.73m2,尿白蛋白与肌酐之比[UACR]超过50mg/g)被随机分配为1:1:1:1:1至26周,标准治疗加皮下cotaduide,滴定至100、300或600μg,或安慰剂每日(双盲),或GLP-1激动剂司美鲁肽1mg,每周一次(开放标签)。共同主要终点是从基线到第14周结束的UACR中相对于安慰剂的绝对和百分比变化。在248名随机患者中,平均年龄67.1岁,19%是女性,平均eGFR为每1.73m255.3mL/min,几何平均值为UACR205.5mg/g(变异系数270.0),46.8%的患者同时接受钠-葡萄糖协同转运蛋白2抑制剂。Cotadutide剂量依赖性地降低了从基线到第14周结束的UACR,在300μg(-43.9%[95%置信区间-54.7至-30.6])和600μg(-49.9%[-59.3至-38.4])时达到显着性。严重的不良事件在不同组之间平衡。600μg的安全性和耐受性与semaglutide相当。因此,我们的研究表明,在T2D和CKD患者中,cotadutide显着降低UACR在标准的治疗之上,具有可接受的耐受性,表明肾脏保护益处需要在更大的研究中得到证实。
    Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD ,estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m2 and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks treatment with standard of care plus subcutaneous cotadutide up-titrated to100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once-weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m2, geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 μg (-43.9% [95%confidence interval -54.7 to -30.6]) and 600 μg (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 μg were comparable to semaglutide. Thus, our study shows that in patients with T2Dand CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study.
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  • 文章类型: Journal Article
    目的:促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3),游离甲状腺素(FT4)和糖尿病肾病(DKD)仍然存在争议,本研究分析了TSH与TSH之间的相关性,2型糖尿病(T2DM)患者FT3、FT4和DKD。
    方法:T2DM患者(1216例)根据血清TSH分为5组,FT3和FT4水平,尿白蛋白排泄率(UACR)的差异,比较估计的肾小球滤过率(eGFR)。二元logistic回归验证了TSH,FT3、FT4和UACR,eGFR。使用受试者工作特征(ROC)曲线分析DKD的TSH和FT3预测值。
    结果:亚临床甲状腺功能减退和明显甲状腺功能减退的T2DM患者中,eGFR降低的白蛋白尿患病率高于甲状腺功能正常的患者。TSH与UACR呈正相关(r=0.133,p<0.001),与eGFR呈正相关(r=-0.218,p<0.001),FT3与UACR呈负相关(r=-0.260,p<0.001),与eGFR呈正相关(r=0.324,p<0.001)。随着TSH从低常值水平向升高水平的变化以及FT3从高常值水平向降低水平的变化,白蛋白尿的患病率逐渐升高,在TSH组和FT3组中,eGFR降低的患病率逐渐升高.在调整了年龄之后,BMI,糖尿病的持续时间,TPOAb,TGAb,吸烟,饮酒,高血压,使用抗糖尿病药物(二甲双胍,钠-葡萄糖协同转运蛋白2抑制剂),HbA1c,CRP,TC,TG,LDL-C,和HDL-C,TSH和FT3均与UACR增加相关(TSH:OR1.253,p=0.001;FT3:OR0.166,p<0.001)和eGFR降低(TSH:OR1.245,p<0.001,FT3:OR0.579,p<0.001),但是在男性中没有发现TSH与eGFR<60mL/min/1.73m2的相关性。FT3的ROC曲线下面积(AUC)大于TSH(FT3:0.64;TSH:0.61)。
    结论:在T2DM患者中,TSH水平升高和FT3水平降低与DKD相关,而是以性别依赖的方式。FT3对DKD有较高的预测价值。
    OBJECTIVE: The relationship between thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and diabetic kidney disease (DKD) is still controversial, and this study analyzed the correlation between TSH, FT3, FT4 and DKD in patients with type 2 diabetes mellitus (T2DM).
    METHODS: T2DM patients (1216) were divided into five groups based on serum TSH, FT3, and FT4 levels, differences in urinary albumin excretion rate (UACR), estimated glomerular filtration rate (eGFR) were compared. Binary logistic regression verified independent correlations among TSH, FT3, FT4 and UACR, eGFR. TSH and FT3 predictive values for DKD were analyzed using receiver operating characteristic (ROC) curves.
    RESULTS: The prevalence of albuminuria with decreased eGFR was higher in T2DM patients with subclinical hypothyroidism and overt hypothyroidism than that in patients with normal thyroid function. TSH positively correlated with UACR (r = 0.133, p < 0.001) and positively correlated with eGFR (r = -0.218, p < 0.001), FT3 negatively correlated with UACR (r = -0.260, p < 0.001) and positively correlated with eGFR (r = 0.324, p < 0.001). With the change from the lower normal level to the increased level of TSH and the change from the higher normal level to the reduced level of FT3, the prevalence of albuminuria gradually increased, the prevalence of decreased eGFR gradually increased in TSH groups and FT3 groups. After adjusting for age, BMI, duration of diabetes, TPOAb, TGAb, smoking, drinking, hypertension, the use of anti-diabetic medications (metformin, sodium-glucose cotransporter 2 inhibitors), HbA1c, CRP, TC, TG, LDL-C, and HDL-C, both TSH and FT3 correlated with increased UACR (TSH: OR 1.253, p = 0.001; FT3: OR 0.166, p < 0.001) and decreased eGFR (TSH: OR 1.245, p < 0.001, FT3: OR 0.579, p < 0.001), but this correlation of TSH with eGFR < 60 mL/min/1.73 m2 was not found in male. The area under the ROC curve (AUC) for FT3 was greater than that for TSH (FT3: 0.64; TSH: 0.61).
    CONCLUSIONS: Increased TSH and reduced FT3 levels were associated with DKD in T2DM patients, but in a sex-dependent manner. FT3 had a higher predictive value for DKD.
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  • 文章类型: Journal Article
    溃疡性结肠炎(UC)和糖尿病肾病(DKD)是具有多方面发病机制的慢性疾病,对临床管理提出了重大挑战。虽然已经做出了大量努力来调查这些疾病的个体原因,UC和DKD之间的相互作用还没有得到很好的理解。本研究旨在通过孟德尔随机化(MR)分析阐明UC和DKD之间的遗传关联。为常见的生物学途径和潜在的临床意义提供新的见解。
    我们利用来自UC和DKD的大规模全基因组关联研究(GWAS)的数据进行了双向双样本MR研究。根据全基因组显著性和严格的统计标准精心选择仪器变量(IVs)。确保稳健的因果推理。各种MR方法,包括方差逆加权(IVW),用于评估UC和DKD之间的因果关系。还进行了敏感性分析以验证我们研究结果的稳健性。
    我们的分析揭示了UC的遗传易感性与DKD易感性增加之间存在显著的因果关系。具体来说,对UC有遗传易感性的个体发生DKD的风险高17.3%.然而,我们没有发现DKD与UC发病风险之间存在因果关系的证据.此外,我们确定了连接UC和DKD的共同遗传风险因素和分子通路,从而突出潜在的治疗靶点。
    这项研究强调了UC和DKD之间复杂的遗传相互作用,提示UC患者发生DKD的风险可能较高.了解这些共同的遗传途径可以促进对有DKD风险的个体的早期检测策略和有针对性的干预措施的发展。最终,这些见解可以改善患有这两种疾病的患者的临床结局.
    UNASSIGNED: Ulcerative colitis (UC) and diabetic kidney disease (DKD) are chronic disorders with multifaceted pathogenesis, posing significant challenges in clinical management. While substantial efforts have been made to investigate the individual causes of these diseases, the interplay between UC and DKD is not well understood. This study aims to elucidate the genetic association between UC and DKD through Mendelian randomization (MR) analysis, offering new insights into common biological pathways and potential clinical implications.
    UNASSIGNED: We conducted a bidirectional two-sample MR study utilizing data from large-scale genome-wide association studies (GWAS) for both UC and DKD. Instrumental variables (IVs) were meticulously selected according to genome-wide significance and stringent statistical criteria, ensuring robust causal inference. Various MR methodologies, including inverse variance weighting (IVW), were employed to assess the causal relationships between UC and DKD. Sensitivity analyses were also performed to validate the robustness of our findings.
    UNASSIGNED: Our analysis revealed a significant causal relationship between genetic predisposition to UC and increased susceptibility to DKD. Specifically, individuals with a genetic susceptibility to UC exhibited a 17.3% higher risk of developing DKD. However, we found no evidence of a causal link between DKD and the risk of developing UC. Additionally, we identified shared genetic risk factors and molecular pathways linking UC and DKD, thereby highlighting potential therapeutic targets.
    UNASSIGNED: This study underscores the intricate genetic interplay between UC and DKD, suggesting that individuals with UC may be at an elevated risk for developing DKD. Understanding these shared genetic pathways could facilitate the development of early detection strategies and targeted interventions for individuals at risk of DKD. Ultimately, these insights could lead to improved clinical outcomes for patients suffering from both conditions.
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  • 文章类型: Journal Article
    目的:评估2型糖尿病(T2D)患者痴呆的可能性,区分有和没有微血管疾病的人。
    方法:利用台湾国家健康保险研究数据库,我们确定了2009年1月1日至2014年12月31日期间新诊断为T2D的个体.多变量Cox比例风险模型用于比较结果的风险。
    结果:与没有微血管疾病的匹配个体相比,患有微血管疾病的个体患全因痴呆的风险显著更高(校正风险比[95%置信区间]1.13[1.09,1.17])。此外,糖尿病肾病和糖尿病神经病变的个体与阿尔茨海默病的风险显著增加相关(1.16[1.02,1.32]和1.14[1.03,1.27]),血管性痴呆(1.21[1.06,1.38]和1.14[1.02,1.28])和其他痴呆(1.11[1.04,1.19]和1.10[1.04,1.16]),分别,与没有微血管疾病的人相比。
    结论:这项全国性的队列研究表明,患有T2D和微血管疾病的患者,特别是糖尿病肾病和糖尿病神经病变,与阿尔茨海默病的风险显著增高有关,血管性痴呆,其他痴呆和全因痴呆比那些没有微血管疾病。
    OBJECTIVE: To assess the likelihood of dementia in individuals with type 2 diabetes (T2D), distinguishing between those with and without microvascular diseases.
    METHODS: Leveraging the National Health Insurance Research Database in Taiwan, we identified individuals newly diagnosed with T2D from 1 January 2009 through 31 December 2014. Multivariable Cox proportional hazard models were used to compare the risk of outcomes.
    RESULTS: Individuals with microvascular disease had a significantly higher risk of all-cause dementia (adjusted hazard ratio [95% confidence interval] 1.13 [1.09, 1.17]) compared with matched individuals without microvascular disease. In addition, individuals with diabetic kidney disease and diabetic neuropathy were associated with a significantly increased risk of Alzheimer\'s disease (1.16 [1.02, 1.32] and 1.14 [1.03, 1.27]), vascular dementia (1.21 [1.06, 1.38] and 1.14 [1.02, 1.28]) and other dementia (1.11 [1.04, 1.19] and 1.10 [1.04, 1.16]), respectively, compared with those without microvascular disease.
    CONCLUSIONS: This nationwide cohort study showed that patients with T2D and microvascular disease, particularly diabetic kidney disease and diabetic neuropathy, were associated with a significantly higher risk of Alzheimer\'s disease, vascular dementia, other dementia and all-cause dementia than those without microvascular disease.
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