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Diabetes mellitus in stable chronic heart failure and the combination with humoral activation, their association, and prediction of 2-year adverse outcomes. Data from the FAR NHL registry 稳定型慢性心力衰竭患者的糖尿病及其与体液激活的结合、两者之间的关联以及两年不良预后的预测。来自 FAR NHL 登记处的数据
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-09-12 DOI: 10.1111/1753-0407.13605
Karel Labr, Jindrich Spinar, Jiri Parenica, Lenka Spinarova, Jan Krejci, Filip Malek, Petr Ostadal, Ondrej Ludka, Jiri Jarkovsky, Klara Benesova, Ruzena Labrova, Monika Spinarova

Background/Aim

The study aims to describe the role of diabetes in patients with heart failure.

Methods

In all, 1052 chronic heart failure patients were included in the FARmacology and NeuroHumoral Activation (FAR NHL) multicenter prospective registry. They had ejection fraction below 50% and were on stable medication for at least 1 month.

Results

More than one-third (38.9%) of the patients had diabetes mellitus (DM). Diabetic patients (N = 409) were older (median 67 vs. 64, p < 0.001), had higher body mass index (BMI) (30 vs. 28 kg/m2, p < 0.001), much more frequently had ischemic heart disease (71 vs. 47%, p < 0.001), hypertension (80 vs. 67%, p < 0.001), dyslipidemia (89 vs. 69%, p < 0.001), worse renal function (estimated glomerular filtration rate [eGFR] median 63 vs. 73 mL/min/1.73 m2, p < 0.001), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) (median 681 vs. 463 pg/mL, p = 0.003). All-cause death, left ventricle assist device implantation, and orthotopic heart transplantation were set as the combined primary end point, which was present in 15.5% (163 patients) within the 2-year follow-up. In the 2-year follow-up, 81.0% of patients with diabetes survived without a primary end point, while 85.4% of the patients without diabetes survived, the difference being on the verge of statistical significance (p = 0.089). DM is a statistically significant predictor of NT-proBNP value in univariate analysis, but it is not an independent predictor in a multivariate analysis. When the NT-proBNP level was high, the presence of DM did not influence the prognosis.

Conclusion

The combination of diabetes and NT-proBNP levels may better stratify the prognosis of patients with chronic heart failure.

背景/目的 该研究旨在描述糖尿病在心力衰竭患者中的作用。 方法 FARmacology and NeuroHumoral Activation(FAR NHL)多中心前瞻性登记共纳入了 1052 名慢性心力衰竭患者。这些患者的射血分数低于 50%,且服用稳定药物至少 1 个月。 结果 超过三分之一(38.9%)的患者患有糖尿病(DM)。糖尿病患者(N = 409)年龄较大(中位数为 67 岁对 64 岁,P < 0.001),体重指数(BMI)较高(30 kg/m2 对 28 kg/m2,P < 0.001),患有缺血性心脏病(71% 对 47%,P < 0.001)、高血压(80% 对 67%,P < 0.001)、血脂异常(89% 对 69%,p <0.001)、肾功能较差(估计肾小球滤过率[eGFR]中位数为 63 对 73 mL/min/1.73 m2,p <0.001)以及 N 端脑钠肽原(NT-proBNP)较高(中位数为 681 对 463 pg/mL,p = 0.003)。全因死亡、左心室辅助装置植入和正位心脏移植被设定为合并的主要终点,在2年的随访中,15.5%的患者(163例)出现了这一情况。在2年的随访中,81.0%的糖尿病患者在未出现主要终点的情况下存活了下来,而85.4%的非糖尿病患者存活了下来,差异接近统计学意义(P = 0.089)。在单变量分析中,DM 对 NT-proBNP 值的预测具有统计学意义,但在多变量分析中,DM 并非独立的预测因素。当 NT-proBNP 水平较高时,DM 的存在并不影响预后。 结论 糖尿病和 NT-proBNP 水平的结合可更好地对慢性心力衰竭患者的预后进行分层。
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引用次数: 0
Association between serum β2-microglobulin and left ventricular hypertrophy in patients with type 2 diabetes mellitus: A cross-sectional study 2 型糖尿病患者血清β2-微球蛋白与左心室肥厚之间的关系:一项横断面研究。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-19 DOI: 10.1111/1753-0407.13599
Yuling Zhang, Guiliang Peng, Weiling Leng, Ying Li, Haiyan Li, Ling Zhou, Lichao Ge, Jiaqing Shao, Xing Li, Min Long

Background

Beta 2-microglobulin (β2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of β2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum β2-MG and LVH in T2DM patients.

Methods

The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum β2-MG levels were measured, and participants were categorized into four groups (Q1–Q4) by their serum β2-MG quartile. The relationship of serum β2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning.

Results

The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum β2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05–1.31); p = 0.006]. When considering β2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09–1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36–2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between β2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of β2-MG for LVH in T2DM patients.

Conclusion

Elevated serum β2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.

背景:β2-微球蛋白(β2-MG)是 I 类主要组织相容性复合体(MHCI)的一个组成部分,最近有报道称它与 2 型糖尿病(T2DM)和心血管疾病有关。然而,β2-MG 与 T2DM 患者左心室肥厚(LVH)的关系仍不清楚。本研究旨在探讨T2DM患者血清β2-MG与左心室肥厚之间的相关性:回顾性分析包括 4602 名符合条件的 T2DM 患者,根据超声心动图检查结果分为 LVH 组和非 LVH 组。测量血清β2-MG水平,并根据血清β2-MG四分位数将参与者分为四组(Q1-Q4)。采用逻辑回归、受限立方样条曲线(RCS)、亚组分析和机器学习等方法评估了血清β2-MG水平与左心室缺血的关系:T2DM患者中LVH的发病率为31.12%。血清β2-MG水平每增加一个标准差,左心室肥厚的患病率就会增加 1.17 倍[OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]。当将β2-MG视为分类变量(四分位数)时,第三季度[OR = 1.36,(95% CI:1.09-1.69);p = 0.007]和第四季度[OR = 1.77,(95% CI:1.36-2.31);p 结论:血清β2-MG升高会导致左心室肥厚的发生率增加 17 倍:血清β2-MG水平的升高可能与T2DM患者左心室肥厚发病率的增加有关,这表明β2-MG在左心室肥厚的发展过程中起着潜在的作用。
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引用次数: 0
Influence of impaired glucose tolerance alone and combined with metabolic syndrome on long-term risk of cardiovascular events and mortality 单纯糖耐量受损和合并代谢综合征对心血管事件和死亡的长期风险的影响。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-19 DOI: 10.1111/1753-0407.13598
Fei Chen, Yifan He, Jinping Wang, Liping Yu, Qiuhong Gong, Yanyan Chen, Yali An, Siyao He, Guangwei Li, Bo Zhang

Background

This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality.

Methods

Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality.

Results

Over the 30-year follow-up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38–2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09–4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19–1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58–2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all-cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group.

Conclusion

IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required.

背景本研究旨在探讨伴有和不伴有代谢综合征(MetS)的糖耐量受损(IGT)对心血管(CV)事件和死亡率影响的潜在差异:本研究纳入了伴有代谢综合征的糖耐量受损患者(IGT_MetS)、不伴有代谢综合征的糖耐量受损患者(IGT_non_MetS)和不伴有代谢综合征的正常糖耐量(NGT)患者(N = 246、N = 294 和 N = 471)。研究采用 Cox 比例危险度回归法检测这三个组别与冠心病事件和死亡率之间的关系:在 30 年的随访期间,57 名(12.1%)NGT_non_MetS 患者、55 名(18.71%)IGT_non_MetS 患者和 74 名(30.08%)IGT_MetS 患者出现了冠心病死亡。调整风险因素后,与 NGT_non_MetS 组相比,IGT_non_MetS 组的 CV 死亡率危险比为 2(95% 置信区间 [CI],1.38-2.91),IGT_MetS 组的 CV 死亡率危险比为 2.96(95% 置信区间 [CI],2.09-4.19)。在心血管事件方面也观察到类似的模式,IGT_non_MetS 组的危险比为 1.49(95% CI,1.19-1.88),IGT_MetS 组的危险比为 1.97(95% CI,1.58-2.47)。敏感性分析显示,与 NGT_non_MetS 组相比,IGT_non_MetS 组和 IGT_MetS 组的危险比显示出更高的全因死亡风险、心肌梗死事件或心肌梗死死亡率以及中风事件或中风死亡率:结论:IGT_non_MetS 会增加心血管死亡和心血管事件的风险。结论:IGT_non_MetS 会增加心血管死亡和心血管事件的风险,而且当它与 MetS 同时发生时,会进一步增加心血管死亡和心血管事件的风险。这表明需要进行积极干预。
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引用次数: 0
Diabetic kidney disease—Recent updates 糖尿病肾病--最新进展。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-18 DOI: 10.1111/1753-0407.13612
Zachary Bloomgarden
<p>The ramifications of the effects of diabetes on the kidney and the relationships of renal disease to the complications of diabetes are manifold, and several recent studies have addressed important aspects of the implications and the management of diabetic kidney disease (DKD).</p><p>An estimate of the prevalence of DKD among persons with type 1 diabetes (T1D) was made based on the National Health and Nutrition Examination Survey (NHANES) database of 19 225 adults in the United States from 2015 to 2018; 47 had T1D, among whom 20 had estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m<sup>2</sup> or urine albumin/creatinine ratio (UACR) ≥30 mg/g, allowing estimates of 1 202 739 adults in the United States with T1D and a weighted estimate that 21.5% of people with T1D in the United States have DKD.<span><sup>1</sup></span> A report from the Centers for Disease Control Wide-Ranging Online Data for Epidemiologic Research database mortality statistics from 1999 to 2020 reflected the dramatic increase in mortality associated with DKD; more than 500 000 deaths were reported among adults with DKD during this period, with an age-adjusted annual mortality rate per 100 000 persons of approximately 2.0 in 1999–2005, increasing to approximately 4.0 in 2007–2010, but then to 22.0 in 2012–2019 and to 25.0 in 2020.<span><sup>2</sup></span> In an analysis suggesting interrelationships between DKD and cognitive function (CF), among 2977 people with type 2 diabetes (T2D) in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) memory in diabetes trial, there was a greater decline over 40 months in CF with standard than with intensive glycemic treatment among those with urine albumin <0.4 mg/dL, whereas those with higher levels of albuminuria had no evidence of benefit with intensive treatment, and for those with eGFR < 60, CF decline was greater with intensive than with standard glycemic treatment. Similarly, CF decline was greater with standard than intensive glycemic treatment in the subset age <60 years, suggesting that T2D with better renal function and lower age might particularly benefit from more intensive glycemic treatment.<span><sup>3</sup></span> There may be a different relationship between age and renal outcome with intensive lifestyle intervention (ILI); in a 12-year follow-up of the Look AHEAD (Action for Health in Diabetes) trial, prespecified analysis of the relationship between the ILI and age showed that among 5112 participants with baseline eGFR ≥ 45, those aged >60 years at baseline randomized to ILI had a 25% lower likelihood of eGFR decreasing to <45 mL/min/1.73 m<sup>2</sup>, whereas this was not seen in the younger participants.<span><sup>4</sup></span></p><p>The optimal blood pressure treatment target is still not certain. The 11 255-person Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing Risk of Vascular Events (ESPRIT) trial included 4359 persons with diabetes with systolic b
糖尿病对肾脏的影响以及肾脏疾病与糖尿病并发症的关系是多方面的,最近的几项研究探讨了糖尿病肾脏疾病(DKD)的影响和管理的重要方面。根据美国国家健康与营养调查(NHANES)数据库对 2015 年至 2018 年美国 19 225 名成人进行的调查,估计了 1 型糖尿病(T1D)患者中 DKD 的患病率;47 人患有 T1D,其中 20 人的估计肾小球滤过率(eGFR)≤60 mL/min/1.73 m2或尿白蛋白/肌酐比值(UACR)≥30 mg/g,因此估计美国有1 202 739名成人患有T1D,加权估计美国21.5%的T1D患者患有DKD。美国疾病控制中心广泛流行病学研究在线数据数据库 1999 年至 2020 年的死亡率统计报告显示,与 DKD 相关的死亡率急剧上升;据报告,在此期间,DKD 成人患者的死亡人数超过 50 万,1999-2005 年每 10 万人的年龄调整后年死亡率约为 2.0,2007-2010 年增至约 4.0,但 2012-2019 年增至 22.0,2020 年增至 25.0。2 在一项表明 DKD 与认知功能 (CF) 之间相互关系的分析中,在 "控制糖尿病心血管风险行动"(ACCORD)糖尿病记忆试验的 2977 名 2 型糖尿病 (T2D) 患者中,尿白蛋白为 0.4 mg/dL 的患者在接受标准血糖治疗 40 个月后的 CF 下降幅度大于接受强化血糖治疗的患者。对于 eGFR &lt; 60 的患者,强化血糖治疗的 CF 下降幅度大于标准血糖治疗。同样,在年龄为 60 岁的亚组中,标准血糖治疗比强化血糖治疗的 CF 下降幅度更大,这表明肾功能较好、年龄较小的 T2D 患者可能尤其能从强化血糖治疗中获益。年龄与强化生活方式干预(ILI)的肾脏结果之间可能存在不同的关系;在Look AHEAD(糖尿病健康行动)试验的12年随访中,对ILI与年龄之间关系的预设分析表明,在基线eGFR≥45的5112名参与者中,基线年龄为60岁、随机接受ILI治疗的参与者eGFR降至45 mL/min/1.73 m2的可能性降低了25%,而年轻参与者则没有出现这种情况。最佳血压治疗目标仍不确定。11 255 人参与的降低收缩压强化治疗对降低血管事件风险的影响(ESPRIT)试验纳入了 4359 名糖尿病患者,他们的收缩压(BP)从基线 147 降至试验时的平均收缩压 119(强化)与 135(标准),随访 3.4 年。心肌梗死(MI)、中风、心力衰竭(HF)、死亡和血管再通的综合终点在强化降压目标下的发生率明显低于标准降压目标,分别为9.7%和11.1%;强化降压治疗使心血管疾病死亡率降低了39%,且降低幅度特别大,具有显著的统计学意义。然而,3.0% 的强化治疗参与者与 1.8% 的对照组参与者相比,肾功能有所下降6 ,这是一个潜在的问题,因为在 ACCORD 血压试验和收缩压干预试验 (SPRINT) 中也有类似的强化降压治疗肾功能下降的报告。7有大量证据表明,血管紧张素受体阻滞剂(ARB)和血管紧张素转换酶抑制剂(ACEi)对 DKD 患者有保护肾脏的作用,但这些药物往往会因肾功能恶化而停用。最近对 18 项符合条件的研究进行的个体患者荟萃分析探讨了在大白蛋白尿慢性肾病 4 期和 5 期患者中使用这些药物的重要问题:在 1739 名 eGFR 为 30(中位数:23)、UACR 中位数为 1215 的参与者中,ACEi 或 ARB 可使肾衰竭或肾移植终末期肾病(ESKD)的风险降低 34%,对有糖尿病和无糖尿病患者的益处相似。最近一项引人关注的研究表明,二甲双胍对 DKD 有肾脏保护作用;在对 2007 年至 2016 年 137 514 例新诊断的 T2D 患者进行随访时,采用倾向得分匹配法,在控制基线肌酐、HbA1c 和其他药物等因素的情况下,接受二甲双胍治疗的患者中,血清肌酐持续加倍至少 3 个月的比例降低了 29%,GFR ≤ 15 mL/min/1.73 m2 的发生率降低了 39%,ESKD 的发生率降低了 45%。 9 使用钠-葡萄糖共转运体-2 抑制剂(SGLT2i)对 DKD 患者有保护作用。对 10 584 名 T2D 和 DKD 患者进行的一项研究显示,索他利氟嗪可将 eGFR 下降≥50%、肾衰竭、eGFR 下降至 15%、需要透析或移植的可能性降低 33%-40%。12 SGLT2i 似乎可降低发生高钾血症的可能性。一项倾向得分匹配研究比较了新开始服用 SGLT2i 和二肽基肽酶 4 抑制剂 (DPP4i) 以及胰高血糖素样肽-1 受体激动剂 (GLP-1RA) 的成人 T2D 患者,使用了一个包含 70 万人的数据集,发现每种药物的高钾血症发生率分别为 25.3% 和 18.5%。SGLT2i与DPP4i相比,高钾血症发生率分别为25.3对18.5;GLP-1RA与DPP4i相比,高钾血症发生率分别为28.5对22.1;GLP-1RA与SGLT2i相比,高钾血症发生率分别为22.1对19.8/1000人年。在一项涉及 43 589 名 DKD 患者的 27 项研究的网络荟萃分析中,联合使用 SGLT2i 和 ACEi/ARB 比单独使用 ACEi/ARB 的高钾血症风险低 61%。人们对使用矿皮质激素拮抗剂 (MRA) 越来越感兴趣,最近的一项比较分析表明,非甾体类 MRA 非格列酮(fineerenone)与 SGLT2i 卡格列净(canagliflozin)对终末期肾病发展的疗效相似,对总死亡率和 CV(心血管)死亡率的影响也相似,但 MRA 与高钾血症相关的可能性更大而不是更小。GLP-1RA semaglutide 在 FLOW(每周一次使用 semagLutide 评估肾功能)试验中进行了研究,该试验有 3533 名 eGFR 为 50-75 和 UACR 为 300 或 eGFR 为 25-50 和 UACR 为 100 的 T2D 患者参加。与安慰剂相比,随机接受每日 1 克塞马鲁肽治疗的患者每 100 患者年的肾脏事件(eGFR、肾衰竭或肾衰竭死亡率下降≥50%)分别为 5.8 例和 7.5 例,NNT 为 20;CV 事件和死亡率分别下降 18% 和 20%,NNT 为 45 例和 39 例。16 一项对 12 项 SGLT2i 试验的荟萃分析研究了在使用 SGLT2i 的同时使用 GLP-1RA 的效果(非随机),结果显示同时使用两种药物的患者的 eGFR 下降斜率降低了 50%。相反,在 FLOW 试验中,有 550 名参与者在基线时服用 SGLT2i;根据血清肌酐和胱抑素 C 计算,这种治疗与 104 周时 eGFR 下降幅度较小有关,但两者之间的相互作用并无统计学意义。对 6696 名开始使用 GLP-1 受体激动剂并加用 SGLT2i 的患者和 8942 名开始使用 SGLT-2 抑制剂并加用 GLP-1 受体激动剂的患者进行的人群数据集分析显示,在 GLP-1RA 基础上加用 SGLT2i 发生严重肾脏事件的可能性降低了 57%,在 SGLT2i 基础上加用 GLP-1RA 发生严重肾脏事件的可能性
{"title":"Diabetic kidney disease—Recent updates","authors":"Zachary Bloomgarden","doi":"10.1111/1753-0407.13612","DOIUrl":"10.1111/1753-0407.13612","url":null,"abstract":"&lt;p&gt;The ramifications of the effects of diabetes on the kidney and the relationships of renal disease to the complications of diabetes are manifold, and several recent studies have addressed important aspects of the implications and the management of diabetic kidney disease (DKD).&lt;/p&gt;&lt;p&gt;An estimate of the prevalence of DKD among persons with type 1 diabetes (T1D) was made based on the National Health and Nutrition Examination Survey (NHANES) database of 19 225 adults in the United States from 2015 to 2018; 47 had T1D, among whom 20 had estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; or urine albumin/creatinine ratio (UACR) ≥30 mg/g, allowing estimates of 1 202 739 adults in the United States with T1D and a weighted estimate that 21.5% of people with T1D in the United States have DKD.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; A report from the Centers for Disease Control Wide-Ranging Online Data for Epidemiologic Research database mortality statistics from 1999 to 2020 reflected the dramatic increase in mortality associated with DKD; more than 500 000 deaths were reported among adults with DKD during this period, with an age-adjusted annual mortality rate per 100 000 persons of approximately 2.0 in 1999–2005, increasing to approximately 4.0 in 2007–2010, but then to 22.0 in 2012–2019 and to 25.0 in 2020.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In an analysis suggesting interrelationships between DKD and cognitive function (CF), among 2977 people with type 2 diabetes (T2D) in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) memory in diabetes trial, there was a greater decline over 40 months in CF with standard than with intensive glycemic treatment among those with urine albumin &lt;0.4 mg/dL, whereas those with higher levels of albuminuria had no evidence of benefit with intensive treatment, and for those with eGFR &lt; 60, CF decline was greater with intensive than with standard glycemic treatment. Similarly, CF decline was greater with standard than intensive glycemic treatment in the subset age &lt;60 years, suggesting that T2D with better renal function and lower age might particularly benefit from more intensive glycemic treatment.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; There may be a different relationship between age and renal outcome with intensive lifestyle intervention (ILI); in a 12-year follow-up of the Look AHEAD (Action for Health in Diabetes) trial, prespecified analysis of the relationship between the ILI and age showed that among 5112 participants with baseline eGFR ≥ 45, those aged &gt;60 years at baseline randomized to ILI had a 25% lower likelihood of eGFR decreasing to &lt;45 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, whereas this was not seen in the younger participants.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The optimal blood pressure treatment target is still not certain. The 11 255-person Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing Risk of Vascular Events (ESPRIT) trial included 4359 persons with diabetes with systolic b","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Management of diabetic ketoacidosis in children: Does early insulin glargine help improve outcomes? 儿童糖尿病酮症酸中毒的管理:早期使用格列卫胰岛素有助于改善疗效吗?
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 DOI: 10.1111/1753-0407.13597
Rebecca Ohman-Hanson, G. Todd Alonso, Laura Pyle, Ryan McDonough, Mark Clements

Background

Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition.

Objective

This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia.

Methods

Patients aged <21 years presenting with DKA to Children's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h of overlap with intravenous [IV] insulin) and Late (<2 h of overlap) cohorts.

Results

We reviewed 546 DKA admissions (365 Early and 181 Late). Rebound hyperglycemia (>180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (<70 mg/dL) during IV insulin administration was higher in the Early group than in the Late group (27% vs. 19%, p = 0.042). Hypoglycemia within 12 h of IV insulin discontinuation was lower in the Early group (16% vs. 26%, p = 0.012). Recurrent ketosis, hypokalemia, and cerebral edema were not different between the groups.

Conclusions

Early glargine administration in pediatric DKA management is safe, decreases the rate of rebound hyperglycemia, and improves the transition to subcutaneous insulin. Hypoglycemia is less frequent following IV insulin discontinuation with early glargine, but the IV insulin rate may need to be reduced to minimize hypoglycemia during IV insulin infusion.

背景:糖尿病酮症酸中毒(DKA)缓解后的反跳性高血糖在 1 型糖尿病儿童患者中很常见,这增加了 DKA 复发的风险,并使向皮下注射胰岛素的过渡复杂化。多项研究表明,在 DKA 治疗期间尽早使用长效胰岛素类似物可安全地改善这种过渡:本研究旨在确定在 DKA 患儿中早期使用格列卫胰岛素是否可预防反跳性高血糖和复发性酮症,同时不会增加低血糖或低钾血症的发生率:我们回顾了546例DKA患儿,这些患儿的年龄与静脉注射[IV]胰岛素重叠4小时:我们回顾了 546 例 DKA 住院病例(365 例早期病例和 181 例晚期病例)。早期组的反跳性高血糖(>180 mg/dL)较低(66% 对 85%,P ≤ 0.0001)。低血糖(结论:在小儿 DKA 治疗中早期使用格列卫是安全的,可降低反跳性高血糖的发生率,并改善向皮下注射胰岛素的过渡。使用早期格列卫停用静脉注射胰岛素后,低血糖发生率较低,但可能需要降低静脉注射胰岛素的速度,以尽量减少静脉注射胰岛素期间的低血糖。
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引用次数: 0
The combined effect of triglyceride–glucose index and high-sensitivity C-reactive protein on cardiovascular outcomes in patients with chronic coronary syndrome: A multicenter cohort study 甘油三酯-葡萄糖指数和高敏 C 反应蛋白对慢性冠状动脉综合征患者心血管预后的联合影响:一项多中心队列研究。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 DOI: 10.1111/1753-0407.13589
Qinxue Li, Ying Song, Zheng Zhang, Jingjing Xu, Zhenyu Liu, Xiaofang Tang, Xiaozeng Wang, Yan Chen, Yongzhen Zhang, Pei Zhu, Xiaogang Guo, Lin Jiang, Zhifang Wang, Ru Liu, Qingsheng Wang, Yi Yao, Yingqing Feng, Yaling Han, Jinqing Yuan

Background

The triglyceride–glucose (TyG) index and high-sensitivity C-reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS).

Methods

A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all-cause death, nonfatal myocardial infarction, and revascularization.

Results

During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE.

Conclusion

Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk populations and guiding management strategies among CCS patients.

背景:甘油三酯-葡萄糖(TyG)指数和高敏C反应蛋白(hsCRP)分别是胰岛素抵抗和全身炎症的常用生物标志物。我们的目的是研究 TyG 和 hsCRP 与慢性冠状动脉综合征(CCS)患者主要不良心血管事件(MACE)的联合关联:本研究共纳入了9421名慢性冠状动脉综合征患者。主要终点定义为包括全因死亡、非致死性心肌梗死和血管重建在内的MACE复合终点:在为期两年的随访期间,共记录了 660 例(7.0%)MACE。根据TyG水平将参与者平均分为三组。与TyG T1组相比,TyG T3组发生MACE的风险明显更高。值得注意的是,在TyG最高三分位数的患者中,hsCRP>3毫克/升与MACE风险增加有显著相关性,而在TyG中低组中结果并不显著。根据 hsCRP 和 TyG 将患者分为六组后,Cox 回归分析显示,TyG T3 组和 hsCRP >3 mg/L 组患者的 MACE 风险明显高于 TyG T1 组和 hsCRP ≤3 mg/L 组。然而,TyG和hsCRP对MACE风险没有明显的交互作用:我们的研究表明,同时评估 TyG 和 hsCRP 可能对识别高危人群和指导 CCS 患者的管理策略很有价值。
{"title":"The combined effect of triglyceride–glucose index and high-sensitivity C-reactive protein on cardiovascular outcomes in patients with chronic coronary syndrome: A multicenter cohort study","authors":"Qinxue Li,&nbsp;Ying Song,&nbsp;Zheng Zhang,&nbsp;Jingjing Xu,&nbsp;Zhenyu Liu,&nbsp;Xiaofang Tang,&nbsp;Xiaozeng Wang,&nbsp;Yan Chen,&nbsp;Yongzhen Zhang,&nbsp;Pei Zhu,&nbsp;Xiaogang Guo,&nbsp;Lin Jiang,&nbsp;Zhifang Wang,&nbsp;Ru Liu,&nbsp;Qingsheng Wang,&nbsp;Yi Yao,&nbsp;Yingqing Feng,&nbsp;Yaling Han,&nbsp;Jinqing Yuan","doi":"10.1111/1753-0407.13589","DOIUrl":"10.1111/1753-0407.13589","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The triglyceride–glucose (TyG) index and high-sensitivity C-reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all-cause death, nonfatal myocardial infarction, and revascularization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP &gt;3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP &gt;3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk populations and guiding management strategies among CCS patients.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.13589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The efficacy of interventions to prevent type 2 diabetes among women with recent gestational diabetes mellitus—A living systematic review and meta-analysis 对近期妊娠糖尿病妇女采取干预措施预防 2 型糖尿病的效果--活体系统综述和荟萃分析。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 DOI: 10.1111/1753-0407.13590
Vivian Y. Lee, Mohammad R. Monjur, Joseph Alvin Santos, Anushka Patel, Rong Liu, Gian Luca Di Tanna, Yashdeep Gupta, Alpesh Goyal, Saumiyah Ajanthan, Devarsetty Praveen, J. K. Lakshmi, H. Asita de Silva, Nikhil Tandon

Background

While previously considered a transient condition, with no lasting adverse impact, gestational diabetes mellitus (GDM) is now a well-established risk factor for developing type 2 diabetes mellitus (T2DM). The risk of developing T2DM appears to be particularly high in the first few years after childbirth, providing a compelling case for early intervention. This review provides an up-to-date systematic review and meta-analysis to assess the effectiveness of interventions to reduce incidence of T2DM in women with a recent history of GDM.

Methods

The search was conducted on October 20, 2023 with an annual surveillance planned for the next 5 years to maintain a living systematic review. The inclusion criteria were randomized controlled trials of any type in women within 5 years of GDM-complicated pregnancy that reported outcomes of T2DM diagnosis or measures of dysglycemia with a follow-up of at least 12 months.

Results

Seventeen studies met our inclusion criteria and have been included in this review. There were 3 pharmacological and 14 lifestyle interventions. Intervention was not associated with significant reduction in the primary outcome of T2DM (risk ratio, 0.78; 95% confidence interval [CI]: 0.43–1.41; p = 0.41; I2 = 79%) compared with the control group (placebo or usual care). However, meta-analysis of the four studies reporting hazard ratios suggested a reduction in diabetes incidence (hazard ratio, 0.68; 95% CI: 0.48–0.97; p = 0.03; I2 = 31%).

Conclusion

This review provides equivocal evidence about the efficacy of interventions to reduce the risk of T2DM in women within 5 years of GDM-complicated pregnancy and highlights the need for further studies, including pharmacotherapy.

背景:妊娠期糖尿病(GDM)以前被认为是一种短暂的疾病,不会产生持久的不良影响,但现在它已成为罹患 2 型糖尿病(T2DM)的一个公认的危险因素。在分娩后的最初几年中,罹患 T2DM 的风险似乎特别高,这为早期干预提供了令人信服的理由。本综述提供了最新的系统综述和荟萃分析,以评估干预措施对降低近期有 GDM 病史的妇女 T2DM 发病率的有效性:检索于 2023 年 10 月 20 日进行,并计划在未来 5 年内每年进行一次监测,以保持系统性综述的活力。纳入标准是对 GDM 并发妊娠 5 年内的妇女进行的任何类型的随机对照试验,这些试验报告了 T2DM 诊断结果或血糖异常测量结果,随访时间至少为 12 个月:结果:17 项研究符合我们的纳入标准,并被纳入本综述。其中有 3 项药物干预和 14 项生活方式干预。干预与 T2DM 主要结果的显著降低无关(风险比为 0.78;95% 置信区间 [CI]:0.43-1.41; p = 0.41; I2 = 79%)。然而,对四项报告危险比的研究进行的荟萃分析表明,糖尿病发病率有所降低(危险比为 0.68;95% 置信区间:0.48-0.97;P = 0.03;I2 = 31%):本综述为降低 GDM 并发妊娠 5 年内妇女 T2DM 风险的干预措施的疗效提供了不明确的证据,并强调了进一步研究(包括药物治疗)的必要性。
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引用次数: 0
Association between estimated glucose disposal rate control level and stroke incidence in middle-aged and elderly adults 中老年人估计葡萄糖处置率控制水平与中风发病率之间的关系。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 DOI: 10.1111/1753-0407.13595
Jiangnan Yao, Feng Zhou, Lingzhi Ruan, Yiling Liang, Qianrong Zheng, Jiaxin Shao, Fuman Cai, Jianghua Zhou, Hao Zhou

Background

To estimate glucose disposal rate (eGDR) as a newly validated surrogate marker of insulin resistance. Few studies have explored the association between changes in eGDR levels and stroke incidence. This study aims to explore the effect of the level of eGDR control on stroke and events.

Methods

Data were obtained from the China Longitudinal Study on Health and Retirement (CHARLS). The eGDR control level was classified using K-means cluster analysis. Logistic regression analysis was used to explore the association between different eGDR control levels and incident stroke. Restrictive cubic spline regression was used to test the potential nonlinear association between cumulative eGDR and stroke incidence.

Results

Of the 4790 participants, 304 (6.3%) had a stroke within 3 years. The odds ratio (OR) was 2.34 (95% confidence interval [CI], 1.42–3.86) for the poorly controlled class 4 and 2.56 (95% CI, 1.53–4.30) for the worst controlled class 5 compared with class 1 with the best controlled eGDR. The OR for well-controlled class 2 was 1.28 (95% CI, 0.79–2.05), and the OR for moderately controlled class 3 was 1.95 (95% CI, 1.14–3.32). In restrictive cubic spline regression analysis, eGDR changes are linearly correlated with stroke occurrence. Weighted quartile and regression analysis identified waist circumference and hypertension as key variables of eGDR for predicting incident stroke.

Conclusions

Poorly controlled eGDR level is associated with an increased risk of stroke in middle-aged and elderly people. Monitoring changes in eGDR may help identify individuals at high risk of stroke early.

背景:估算葡萄糖处置率(eGDR),将其作为新近验证的胰岛素抵抗替代标志物。很少有研究探讨 eGDR 水平的变化与脑卒中发病率之间的关系。本研究旨在探讨 eGDR 控制水平对脑卒中和脑卒中事件的影响:方法:数据来自中国健康与退休纵向研究(CHARLS)。方法:数据来自中国健康与退休纵向研究(CHARLS),采用 K-均值聚类分析法对 eGDR 控制水平进行分类。采用逻辑回归分析探讨不同 eGDR 控制水平与卒中事件之间的关系。限制性三次样条回归用于检验累积 eGDR 与脑卒中发病率之间的潜在非线性关系:结果:在 4790 名参与者中,有 304 人(6.3%)在 3 年内发生了中风。与 eGDR 控制最好的 1 级相比,控制较差的 4 级的几率比 (OR) 为 2.34(95% 置信区间 [CI],1.42-3.86),控制最差的 5 级的几率比 (OR) 为 2.56(95% 置信区间 [CI],1.53-4.30)。控制良好的 2 级的 OR 值为 1.28(95% CI,0.79-2.05),控制中等的 3 级的 OR 值为 1.95(95% CI,1.14-3.32)。在限制性三次样条回归分析中,eGDR 的变化与中风发生率呈线性相关。加权四分位和回归分析确定腰围和高血压是 eGDR 预测卒中发生的关键变量:结论:控制不良的 eGDR 水平与中老年人中风风险增加有关。监测 eGDR 的变化有助于及早发现中风高危人群。
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引用次数: 0
Clinical characteristics and complication risks in data-driven clusters among Chinese community diabetes populations 中国社区糖尿病人群数据驱动集群的临床特征和并发症风险。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 DOI: 10.1111/1753-0407.13596
Binqi Li, Zizhong Yang, Yang Liu, Xin Zhou, Weiqing Wang, Zhengnan Gao, Li Yan, Guijun Qin, Xulei Tang, Qin Wan, Lulu Chen, Zuojie Luo, Guang Ning, Weijun Gu, Yiming Mu

Background

Novel diabetes phenotypes were proposed by the Europeans through cluster analysis, but Chinese community diabetes populations might exhibit different characteristics. This study aims to explore the clinical characteristics of novel diabetes subgroups under data-driven analysis in Chinese community diabetes populations.

Methods

We used K-means cluster analysis in 6369 newly diagnosed diabetic patients from eight centers of the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. The cluster analysis was performed based on age, body mass index, glycosylated hemoglobin, homeostatic modeled insulin resistance index, and homeostatic modeled pancreatic β-cell functionality index. The clinical features were evaluated with the analysis of variance (ANOVA) and chi-square test. Logistic regression analysis was done to compare chronic kidney disease and cardiovascular disease risks between subgroups.

Results

Overall, 2063 (32.39%), 658 (10.33%), 1769 (27.78%), and 1879 (29.50%) populations were assigned to severe obesity-related and insulin-resistant diabetes (SOIRD), severe insulin-deficient diabetes (SIDD), mild age-associated diabetes mellitus (MARD), and mild insulin-deficient diabetes (MIDD) subgroups, respectively. Individuals in the MIDD subgroup had a low risk burden equivalent to prediabetes, but with reduced insulin secretion. Individuals in the SOIRD subgroup were obese, had insulin resistance, and a high prevalence of fatty liver, tumors, family history of diabetes, and tumors. Individuals in the SIDD subgroup had severe insulin deficiency, the poorest glycemic control, and the highest prevalence of dyslipidemia and diabetic nephropathy. Individuals in MARD subgroup were the oldest, had moderate metabolic dysregulation and the highest risk of cardiovascular disease.

Conclusion

The data-driven approach to differentiating the status of new-onset diabetes in the Chinese community was feasible. Patients in different clusters presented different characteristics and risks of complications.

背景:欧洲人通过聚类分析提出了新型糖尿病表型,但中国社区糖尿病人群可能表现出不同的特征。本研究旨在通过数据驱动分析,探讨中国社区糖尿病人群中新型糖尿病亚组的临床特征:方法:我们对来自 REACTION(中国糖尿病患者风险评估)研究 8 个中心的 6369 名新诊断糖尿病患者进行了 K-均值聚类分析。聚类分析基于年龄、体重指数、糖化血红蛋白、同源模型胰岛素抵抗指数和同源模型胰岛β细胞功能指数。临床特征采用方差分析(ANOVA)和卡方检验进行评估。采用逻辑回归分析比较不同亚组之间的慢性肾病和心血管疾病风险:总体而言,2063 人(32.39%)、658 人(10.33%)、1769 人(27.78%)和 1879 人(29.50%)分别被归入严重肥胖相关性和胰岛素抵抗性糖尿病(SOIRD)、严重胰岛素缺乏性糖尿病(SIDD)、轻度年龄相关性糖尿病(MARD)和轻度胰岛素缺乏性糖尿病(MIDD)亚组。轻度胰岛素缺乏性糖尿病(MIDD)亚组中的个体风险负担较低,相当于糖尿病前期,但胰岛素分泌减少。SOIRD 亚组组员肥胖、胰岛素抵抗、脂肪肝、肿瘤、糖尿病家族史和肿瘤发病率高。SIDD 亚组中的患者胰岛素严重不足,血糖控制最差,血脂异常和糖尿病肾病发病率最高。MARD亚组的患者年龄最大,代谢失调程度中等,罹患心血管疾病的风险最高:结论:以数据为导向区分中国社区新发糖尿病状况的方法是可行的。不同群组的患者具有不同的特征和并发症风险。
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引用次数: 0
Probiotic treatment with viable α-galactosylceramide-producing Bacteroides fragilis reduces diabetes incidence in female nonobese diabetic mice 用能产生α-半乳糖酰胺的脆弱拟杆菌进行益生菌治疗可降低雌性非肥胖糖尿病小鼠的糖尿病发病率。
IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-08-13 DOI: 10.1111/1753-0407.13593
Camilla H. F. Hansen, Danica Jozipovic, Line F. Zachariassen, Dennis S. Nielsen, Axel K. Hansen, Karsten Buschard

Background

We aimed to investigate whether alpha-galactosylceramide (α-GalCer)-producing Bacteroides fragilis could induce natural killer T (NKT) cells in nonobese diabetic (NOD) mice and reduce their diabetes incidence.

Methods

Five-week-old female NOD mice were treated orally with B. fragilis, and islet pathology and diabetes onset were monitored. Immune responses were analyzed by flow cytometry and multiplex technology. Effects of ultraviolet (UV)-killed α-GalCer-producing B. fragilis and their culture medium on invariant NKT (iNKT) cells were tested ex vivo on murine splenocytes, and the immunosuppressive capacity of splenocytes from B. fragilis-treated NOD mice were tested by adoptive transfer to nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice.

Results

B. fragilis reduced the diabetes incidence from 69% to 33% and the percent of islets with insulitis from 40% to 7%, which doubled the serum insulin level compared with the vehicle-treated control mice. Furthermore, the early treatment reduced proinflammatory mediators in the serum, whereas the proportion of CD4+ NKT cell population was increased by 33%. B. fragilis growth media stimulated iNKT cells and anti-inflammatory M2 macrophages ex vivo in contrast to UV-killed bacteria, which had no effect, strongly indicating an α-GalCer-mediated effect. Adoptive transfer of splenocytes from B. fragilis-treated NOD mice induced a similar diabetes incidence as splenocytes from untreated NOD mice.

Conclusions

B. fragilis induced iNKT cells and M2 macrophages and reduced type 1 diabetes in NOD mice. The protective effect seemed to be more centered on gut–pancreas interactions rather than a systemic immunosuppression. B. fragilis should be considered for probiotic use in individuals at risk of developing type 1 diabetes.

背景:我们的目的是研究产生α-半乳糖甘油酰胺(α-GalCer)的脆弱拟杆菌(Bacteroides fragilis)是否能诱导非肥胖糖尿病(NOD)小鼠体内的自然杀伤T细胞(NKT)并降低其糖尿病发病率:方法:用脆弱拟杆菌口服治疗5周大的雌性NOD小鼠,并监测胰岛病理学和糖尿病发病情况。采用流式细胞术和多重技术分析免疫反应。在小鼠脾脏细胞体外测试了紫外线(UV)杀死的产α-GalCer的脆弱拟杆菌及其培养基对不变NKT(iNKT)细胞的影响,并通过将脆弱拟杆菌处理过的NOD小鼠脾脏细胞收养转移到非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠体内测试了其免疫抑制能力:结果:与用药物治疗的对照组小鼠相比,B. fragilis能将糖尿病发病率从69%降至33%,将胰岛炎小鼠的比例从40%降至7%,使血清胰岛素水平提高一倍。此外,早期治疗减少了血清中的促炎介质,而CD4+ NKT细胞的比例则增加了33%。B.fragilis生长培养基能刺激体内iNKT细胞和抗炎M2巨噬细胞,而紫外线杀死的细菌则没有作用,这有力地表明了α-GalCer介导的作用。经B. fragilis处理的NOD小鼠脾细胞的采纳转移诱导的糖尿病发病率与未经处理的NOD小鼠脾细胞的发病率相似:结论:B. fragilis能诱导iNKT细胞和M2巨噬细胞,降低NOD小鼠的1型糖尿病发病率。这种保护作用似乎更集中于肠道与胰腺之间的相互作用,而不是全身性的免疫抑制。对于有患1型糖尿病风险的人来说,应考虑使用B.fragilis益生菌。
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引用次数: 0
期刊
Journal of Diabetes
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