Journal of Diabetes最新文献_第2页

The Role of Incretins in Obstructive Sleep Apnea “GLP1RAs and GLP1RA/GIPRAs in OSA” 肠促胰岛素在阻塞性睡眠呼吸暂停中的作用“GLP1RAs和GLP1RA/GIPRAs in OSA”。

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-11-20 DOI: 10.1111/1753-0407.70170

Ana Lucia Fuentes, Gurleen Dhami, Jeremy Pettus, Praveen Akuthota, Atul Malhotra

Mechanisms of action and effects of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists on multiple organ systems relevant to obstructive sleep apnea and cardiometabolic health.

GLP-1受体激动剂和双GLP-1/GIP受体激动剂对阻塞性睡眠呼吸暂停和心脏代谢健康相关多器官系统的作用机制和影响

引用次数: 0

Recent Articles—Skeletal Muscle and Other Topics in Diabetes 最近的文章-骨骼肌和其他主题的糖尿病。

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-11-18 DOI: 10.1111/1753-0407.70169

Zachary Bloomgarden

<p>This commentary summarizes recently published research, giving several important findings. Deficiency of skeletal muscle appears, like excess of visceral fat, to strongly contribute to the development of diabetes. Concerns about GLP-1RA in contributing to low muscle mass may be overstated, with the benefits of the class appearing to outweigh adverse effects; however, approaches to prevention of muscle loss with GLP-1RA and with diabetes itself are important. Low muscle strength is a strong predictor of mortality and frailty; and resistance exercise may be a key approach in patient management. Cardiovascular risks differ between type 1 diabetes (T1D) and type 2 diabetes (T2D), with risk reduction important for both.</p><p>Obesity treatments (semaglutide, tirzepatide, and bariatric surgery) generally lower the risk of obesity-related cancers, but bariatric surgery may increase the risk for procedure-related cancers. Metabolic syndrome raises the risk of developing Parkinson's disease. Both hypoglycemia and higher levels of HbA1c are associated with the development of dementia.</p><p>In analysis of development of T2D among participants with prediabetes in the UK biobank, the 12% with sarcopenia at baseline, based on lower handgrip strength, muscle mass and walking pace, had 19.3% versus 14.9% T2D rates over a mean 11.4 year-follow-up. Those with sarcopenia had, on average, slightly higher baseline BMI, but interestingly the association of sarcopenia with T2D was particularly great among those with waist: hip ratio < 0.9, suggesting sarcopenia to be an additional factor, like excess visceral fat, in causing development of T2D [<span>1</span>].</p><p>Botte and coworkers offer an interesting perspective on the role of low muscle strength (related both to low muscle mass and low muscle quality) in metabolic disorders [<span>2</span>]. Given the recognition of the importance of sarcopenia, it is instructive to summarize portions of their analysis. Low muscle strength is associated with ~2.5-fold greater all-cause mortality [<span>3-5</span>]. With aging, myosteatosis may have a particularly great impact on muscle strength, predicting fall risk and all-cause mortality more than muscle mass in older adults [<span>6</span>]. BMI correlates with higher appendicular lean mass, but not with grip strength [<span>7</span>]. Potential sarcopenia treatment approaches include selective androgen receptor modulators (SARMS) [<span>8</span>], growth hormone secretagogues [<span>9</span>], ghrelin agonists, and fast-twitch skeletal muscle troponin inhibitors [<span>10</span>], but at present none of these appear satisfactory. Recent efforts have targeted the myostatin pathway, which physiologically leads to inhibition of muscle growth [<span>11</span>]. Bimagrumab, an activin receptor antagonist, promotes skeletal muscle growth and fat loss, and may have benefits for bone health. While activins are also involved in reproductive hormone regulation, the selectivity

这篇评论总结了最近发表的研究，给出了几个重要的发现。骨骼肌缺乏，就像内脏脂肪过多一样，是糖尿病的重要诱因。对GLP-1RA导致低肌肉质量的担忧可能被夸大了，该类药物的益处似乎大于其副作用；然而，预防GLP-1RA和糖尿病本身的肌肉损失的方法是重要的。低肌肉力量是死亡率和虚弱的一个强有力的预测指标；抗阻运动可能是患者管理的关键方法。1型糖尿病（T1D）和2型糖尿病（T2D）的心血管风险不同，降低风险对两者都很重要。肥胖治疗（西马鲁肽、替西帕肽和减肥手术）通常可以降低肥胖相关癌症的风险，但减肥手术可能会增加手术相关癌症的风险。代谢综合征会增加患帕金森病的风险。低血糖和较高的HbA1c水平都与痴呆的发展有关。在英国生物银行对糖尿病前期患者T2D发展的分析中，12%的基线肌少症患者（基于较低的握力、肌肉质量和步行速度）在平均11.4年的随访中有19.3%对14.9%的T2D发病率。平均而言，肌肉减少症患者的基线BMI略高，但有趣的是，肌肉减少症与T2D的关联在腰臀比为0.9的人群中尤为明显，这表明肌肉减少症与内脏脂肪过多一样，是导致T2D[1]发展的另一个因素。Botte和他的同事们提出了一个有趣的观点，即低肌肉力量（与低肌肉质量和低肌肉质量相关）在代谢紊乱中的作用。鉴于认识到肌肉减少症的重要性，总结他们的部分分析是有指导意义的。低肌力与2.5倍的全因死亡率相关[3-5]。随着年龄的增长，肌骨化病可能对肌肉力量有特别大的影响，预测老年人跌倒风险和全因死亡率比肌肉质量更重要。BMI与较高的阑尾瘦质量相关，但与握力无关。潜在的肌少症治疗方法包括选择性雄激素受体调节剂（SARMS）[8]、生长激素分泌剂[9]、生长素激动剂和快速收缩骨骼肌肌钙蛋白抑制剂[10]，但目前这些方法都不令人满意。最近的研究针对肌肉生长抑制素途径，该途径在生理上导致肌肉生长的抑制。Bimagrumab是一种激活素受体拮抗剂，促进骨骼肌生长和脂肪减少，可能对骨骼健康有益。虽然激活素也参与生殖激素调节，但bimagrumab对ActRIIB的选择性及其药代动力学似乎限制了其对生殖激素通路的影响。然而，尽管bimagrumab与瘦体重的增加有关，但它似乎并没有改善功能能力，无论是力量还是身体表现[13,14]。在一项针对70岁非肥胖者的大型研究中，bimagrumab增加了瘦体重，减少了脂肪量，但没有增加活动量，副作用包括腹泻、肌肉痉挛、胰腺和肝脏酶[15]升高。替西帕肽[16]和半马鲁肽[17]均与改善肌肉功能有关，利拉鲁肽配合抗阻训练可增加瘦质量并减轻体重[18]。因此，肠促胰岛素受体激活剂，特别是与阻力运动结合使用时，可能是治疗肥胖和肌肉减少症的最佳方法。Pandey等人分析了semaglutide与安慰剂对1145例保留射血分数（HFpEF）心力衰竭患者的影响，发现semaglutide对生活质量的最大改善是在虚弱bbb水平最高的患者亚群中发现的。这意味着，由于担心这些患者会有更多的副作用或更大程度的肌肉损失导致虚弱，而不是虚弱是使用强效GLP-1RA的相对禁禁症，虚弱似乎是使用这些药物的一个特别强烈的适应症。在英国生物银行（UK Biobank）对467 200名参与者进行了14.6年的随访，其中177 407人患有基于腰围、高血压、低HDL、高甘油三酯或高血糖的代谢综合征（MS）， 3222人患上帕金森病（PD）；经临床因素和多基因PD风险评分调整后，MS与PD增加39%相关，风险与MS成分的数量成正比。Patsoukaki等人。对瑞典国家登记的38351例1型糖尿病（T1D）和366575例T2D患者进行了5年随访，报告了心血管疾病发生率和死亡率及其与CV危险因素的关系。50岁前，心肌梗死（MI）在T2D中的发生率比T1D高54%，但在50 - 59岁、60-69岁和70岁以上时，心肌梗死在T2D中的发生率分别比T1D低17%、33%和35%。50岁之前，T2D患者发生心力衰竭的可能性比T1D患者高60%，但在50岁及以上时，T1D和T2D患者的风险相似。总体而言，T2D患者卒中的可能性比T1D患者低9%，在50-59岁、60-69岁和70岁以上年龄，T2D患者的CV死亡率分别比T1D患者低19%、25%和20%。进一步的分析揭示了个体危险因素与心血管疾病的特定关联。女性患心血管疾病的风险降低了35%。与HbA1c为6.3的患者相比，HbA1c为7.7的患者总体心血管疾病风险增加24%，心肌梗死风险增加34%，心血管疾病死亡率增加14%。较高的低密度脂蛋白胆固醇与心肌梗死的显著增加有关，但令人惊讶的是，与较低的心力衰竭和心血管疾病死亡风险有关。该分析的一个主要结论是，降低心血管疾病风险对T1D和T2D同样重要，特别是在老年人群中，这使得作者认为应该在T1D人群中进行SGLT2抑制剂、GLP-1受体激动剂和矿化皮质激素拮抗剂的心脏肾脏益处研究，就像对T2D所做的那样。一项有趣的研究观察了在倾向评分调整的对照组中，用二肽基肽酶4抑制剂（DPP4i）治疗的肥胖相关癌症（OAC）（乳腺癌、结直肠、胆囊癌、肝癌、多发性骨髓瘤、食管癌、卵巢癌、胰腺癌、肾癌、贲门癌、甲状腺癌和子宫癌）与用semaglutide（64178对配对，1.5年随访）和替西帕肽（19682对配对，0.8年随访）治疗的肥胖相关癌症（OAC）的发生率。在TriNetX电子健康记录网络[22]中进行胃旁路手术（9642对匹配，4.9年随访）。西马鲁肽组总OAC可能性降低12%，替西帕肽组降低16%（但不显著），减肥手术组降低15%。对于特定部位，使用西马鲁肽，结直肠癌减少20%，肝癌减少25%，胰腺癌减少24%；使用替西肽卵巢癌降低69%；通过减肥手术，肝癌减少44%，子宫癌减少41%，食管癌和贲门癌分别增加4.8倍和10.5倍。考虑到GLP-1RA的随访时间相对较短，个体癌症的数量较少，结果可能存在偏差，作者认为医生可能不太可能在早期症状随后与恶性肿瘤相关的患者中开始使用这些药物，但总OAC的发现确实支持肥胖与恶性肿瘤相关的认识，并表明减少肥胖的措施可能有利于减少恶性肿瘤。另一个值得关注的发现是，减肥手术增加了食管癌和贲门癌，这与这些手术令人担忧的并发症相一致。一项对40项研究的荟萃分析显示，有低血糖史的糖尿病患者患痴呆的可能性增加1.5倍，阿尔茨海默病和血管性痴呆的研究结果也类似，一项研究显示痴呆与低血糖发作次数较多有关。HbA1c水平越高，患痴呆的可能性越大。检查HbA1c变异性和糖尿病病程信息的研究表明，这些因素也与痴呆的可能性增加有关。作者声明无利益冲突。

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引用次数: 0

Comment on “Sitagliptin, a DPP-4 Inhibitor, Effectively Promotes the Healing of Diabetic Foot Ulcer: A Randomized Controlled Trial” “西格列汀，DPP-4抑制剂，有效促进糖尿病足溃疡愈合：一项随机对照试验”评论

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-11-05 DOI: 10.1111/1753-0407.70165

Sabika Ayesha, Umaima Parveen, Noor Un Nisa Irshad

<p>The study conducted by Gao et al. offers valuable evidence regarding the therapeutic potential of sitagliptin in the management of diabetic foot ulcers (DFUs) [<span>1</span>]. The authors have identified opportunities for adjunctive therapies in a condition that continues to be a morbidity by demonstrating enhancements in ulcer healing and endothelial progenitor cell (EPC) mobilization. Nonetheless, several methodological and interpretative considerations need discussion to place these results in a broader clinical context.</p><p>A major concern is the trial's inadequate blinding. The authors state that “blinding was applied exclusively to the personnel responsible for performing area calculations and laboratory evaluator evaluations,” yet patients and treating clinicians were aware of allocation because no placebo was used. This is not a true double-blind study and risks performance and observer bias. In double-blind randomized controlled trials, such as the protocol by O'Reilly et al. [<span>2</span>], both patients and clinicians are blinded to ensure wound care and unbiased outcome assessment. Awareness of sitagliptin could have influenced wound care intensity, follow-up decisions, or judgments of healing, exaggerating the benefit.</p><p>Second, the lack of standardized conventional therapy further complicates interpretation. “Conventional therapy” was described broadly to include vasodilators, neurotrophic agents, antibiotics, and wound debridement, but administration was left to the clinician's discretion. In contrast to O'Reilly et al., where standard wound care methods were routinely implemented, such diversity presents significant confounding factors. If the sitagliptin group received more consistent background therapy, observed differences in healing may reflect uneven supportive care rather than a true pharmacologic effect.</p><p>Third, the outcome definition is limited. Ulcer healing was defined strictly as 100% area reduction, with substantial partial improvements (e.g., 80%–99%) excluded from the primary endpoint. This all-or-nothing approach neglects clinically meaningful outcomes. As Gottrup et al. emphasized [<span>3</span>], wound-healing studies should also consider infection, pain, resource use, and cost-effectiveness. Moreover, while Gao et al. reported CD34+ and SDF-1α changes, reliance on surrogate endpoints is insufficient. Pichu et al. review that biomarker data alone cannot substitute for patient-centered outcomes or hard endpoints such as amputation or recurrence [<span>4</span>].</p><p>Finally, the short follow-up duration represents a significant methodological flaw. Follow-up was capped at 12 weeks or until complete healing. However, it frequently takes several months for Wagner Grades 3–4 ulcers to close. In order to evaluate healing, safety, and amputation outcomes, patients with advanced DFUs treated with cryopreserved umbilical cord were monitored for a year in the Marston et al. study [<span>5</span>]. Limit

Gao等人的研究为西格列汀在糖尿病足溃疡（DFUs）治疗中的治疗潜力提供了有价值的证据。作者通过证明溃疡愈合和内皮祖细胞（EPC）动员的增强，确定了在持续发病的情况下辅助治疗的机会。尽管如此，需要讨论一些方法学和解释性的考虑，以便将这些结果置于更广泛的临床背景下。一个主要的担忧是该试验的盲法不充分。作者指出，“盲法只适用于负责执行区域计算和实验室评估人员评估的人员”，然而患者和治疗临床医生都知道分配，因为没有使用安慰剂。这不是一个真正的双盲研究，存在表现和观察者偏差的风险。在双盲随机对照试验中，如O'Reilly等人的方案，患者和临床医生都是盲的，以确保伤口护理和公正的结果评估。对西格列汀的认识可能影响了伤口护理强度、随访决定或愈合判断，夸大了其益处。其次，缺乏标准化的常规治疗方法进一步使解释复杂化。“常规治疗”被广泛地描述为包括血管扩张剂、神经营养剂、抗生素和伤口清创，但给药则由临床医生自行决定。与O'Reilly等人相比，常规实施标准伤口护理方法，这种多样性带来了显著的混淆因素。如果西格列汀组接受更一致的背景治疗，观察到的愈合差异可能反映了不均衡的支持治疗，而不是真正的药理作用。第三，结果定义是有限的。溃疡愈合被严格定义为100%的面积缩小，主要终点排除了实质性的部分改善（例如80%-99%）。这种全有或全无的方法忽略了临床有意义的结果。正如Gottrup等人强调的那样，伤口愈合研究还应考虑感染、疼痛、资源使用和成本效益。此外，虽然Gao等人报道了CD34+和SDF-1α的变化，但对替代终点的依赖是不够的。Pichu等人回顾了单独的生物标志物数据不能替代以患者为中心的结果或硬终点，如截肢或复发bb0。最后，随访时间短是一个重要的方法缺陷。随访时间为12周或直至完全愈合。然而，瓦格纳3-4级溃疡通常需要几个月的时间才能愈合。为了评估愈合、安全性和截肢结果，在Marston等人的研究中，对使用低温保存脐带治疗的晚期dfu患者进行了为期一年的监测。将观察限制在12个有审查偏差的风险，在这个短时间内没有愈合的溃疡被错误地标记为“无效”。这种截断可能会限制长期的可靠性和低估实际的愈合潜力。综上所述，Gao等人提供了促进DFU愈合的重要证据。然而，盲法、背景治疗标准化、结果测量和随访时间限制可能会限制普遍性和夸大疗效。为了确定西格列汀治疗DFU的实际功能，需要更彻底的随机对照试验，严格的盲法，标准化的护理和延长的随访。概念化：Sabika Ayesha， Umaima Parveen。数据管理：Sabika Ayesha， Umaima Parveen。写作原稿准备：Sabika Ayesha， Umaima Parveen。调查、监督和写作审查：Noor Un Nisa irshhad。所有作者都阅读并批准了最终的手稿。作者没有什么可报告的。作者没有什么可报告的。作者声明无利益冲突。

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引用次数: 0

Long-Term Effects of Intensive Lifestyle Intervention on Cardiometabolic Outcomes in Patients With Diabetes in Real-World Clinical Practice: A 15-Year Longitudinal Study 现实世界临床实践中强化生活方式干预对糖尿病患者心脏代谢结局的长期影响：一项15年的纵向研究

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-11-05 DOI: 10.1111/1753-0407.70153

Abdelrahman Khater, Marwa Al-Badri, Tareq Salah, Shilton E. Dhaver, Karim Kibaa, Osama Hamdy

Introduction

We previously demonstrated that achieving and maintaining ≥ 7% weight loss at 1 year in patients with diabetes (DM), through multidisciplinary intensive lifestyle intervention (ILI) in real-world clinical practice, predicts improvement in cardiometabolic outcomes at 5 and 10 years. In this prospective follow-up, we report 15-year results.

Methods

We evaluated 122 patients with DM and obesity (mean age 53.2 ± 10.0 years, 68% females, 90.2% type 2 DM, mean DM duration 9.1 ± 8.6 years, mean BMI 38.4 ± 5.2 kg/m²) who completed a 12-week ILI program. The cohort achieved an average weight loss of 10.7 ± 4.6 kg (−9.6%, p < 0.001) at 12 weeks and was divided into two groups at 1 year: group A, who maintained < 7% weight loss (47.5%) and group B, who maintained ≥ 7% weight loss (52.5%).

Results

At 15 years, the cohort maintained an average weight loss of 8.6 ± 11.9 kg (−7.6%, p < 0.001). Group B demonstrated superior sustained weight loss (12.9 ± 12.0 kg, −11.0%) compared to group A (3.8 ± 10.0 kg, −4.0%) with p < 0.001 between groups. A1C in group B improved from 7.3% ± 1.1% to 6.3% ± 0.8% at 12 weeks and remained at 7.3% ± 1.5% at 15 years, while group A's A1C increased from 6.7% ± 0.9% to 7.9% ± 1.8% (p = 0.04 between groups). Both groups maintained LDL- and HDL-cholesterol improvements, but group A experienced significant worsening of serum triglycerides.

Conclusions

ILI in real-world clinical practice that results in ≥ 7% weight loss at 1 year in patients with DM and obesity is associated with continued improvement in cardiometabolic outcomes at 15 years.

我们之前证明，在现实世界的临床实践中，通过多学科强化生活方式干预（ILI），糖尿病（DM）患者在1年内实现并维持≥7%的体重减轻，可以预测5年和10年心脏代谢结果的改善。在这项前瞻性随访中，我们报告了15年的结果。方法122例糖尿病合并肥胖患者（平均年龄53.2±10.0岁，68%为女性，90.2%为2型糖尿病患者，平均糖尿病病程9.1±8.6年，平均BMI 38.4±5.2 kg/m2）完成了为期12周的ILI项目。该队列在12周时平均体重减轻10.7±4.6 kg (- 9.6%, p < 0.001)，并在1年时分为两组：A组保持7%的体重减轻（47.5%），B组保持≥7%的体重减轻（52.5%）。结果在15年时，该队列保持了8.6±11.9 kg的平均体重减轻（- 7.6%,p < 0.001）。与A组（3.8±10.0 kg,−4.0%）相比，B组表现出更好的持续体重减轻（12.9±12.0 kg,−11.0%），组间p <； 0.001。12周时，B组糖化血红蛋白由7.3%±1.1%提高到6.3%±0.8%，15年后维持在7.3%±1.5%，而A组糖化血红蛋白由6.7%±0.9%提高到7.9%±1.8%（组间p = 0.04）。两组低密度脂蛋白和高密度脂蛋白胆固醇均有改善，但A组血清甘油三酯明显恶化。结论：在现实世界的临床实践中，糖尿病和肥胖患者在1年内体重减轻≥7%与15年心脏代谢结果的持续改善相关。

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引用次数: 0

Diabetic Kidney and Liver Disease Concepts 糖尿病肾病和肝病的概念。

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-10-30 DOI: 10.1111/1753-0407.70163

Zachary T. Bloomgarden

<p>Using individual-level data from 23 340 participants in four placebo-controlled trials, EMPA-REG OUTCOME (7020 people with T2D and previous ASCVD), EMPEROR-Reduced and EMPEROR-Preserved (9711 with heart failure), and EMPA-KIDNEY (6609 with CKD at risk of progression), the authors studied the benefit of the sodium-glucose countertransporter 2 inhibitor (SGLT2i) empagliflozin when albuminuria is low, in the absence of diabetes, and among those with large acute estimated glomerular filtration rate (eGFR) dips on initiation of treatment, calculating off-treatment dip-free eGFR slopes by dividing the difference between off-treatment eGFR and randomization eGFR by the time between the two measurements in the 10 630 (45.5%) participants with measurement of off-treatment eGFR after discontinuing study treatment, of whom 6250 were allocated to empagliflozin [<span>1</span>]. The independent predictors of larger acute eGFR dips included older age (0.9% larger dip per 10 years), higher eGFR (4.6% larger dip for eGFR ≥ 85 vs. < 37 mL/min per 1.73 m<sup>2</sup>) and level of albuminuria (2.9% larger dip for urine albumin/creatinine ratio [UACR] ≥ 324 vs. < 6 mg/g), renin–angiotensin system inhibitor and diuretic use (1.1% and 0.8% larger dips with use vs. nonuse, respectively), higher systolic blood pressure (0.9% larger dip per 17 mmHg), lower hematocrit (0.9% larger dip per 4.8%), and lower BMI (0.5% larger dip per 5.8 kg/m<sup>2</sup>). A 4-week eGFR dip of more than 14% was seen in 2948 (24.5%) of 12 031 participants in the empagliflozin groups and 1219 (12.5%) of 9761 participants in the placebo groups, with 311 (2.6%) of those randomized to empagliflozin versus 154 (1.6%) of participants receiving placebo having an acute eGFR dip of more than 30%. The likelihood of a 50% or greater increase in follow-up serum creatinine among those allocated to empagliflozin was reduced by 20%, regardless of predicted size of acute eGFR dip, diabetes status, baseline eGFR, or albuminuria, previous heart failure, or by baseline NT-proBNP. Similarly, allocation to empagliflozin reduced the risk of acute kidney injury by 27% regardless of predicted size of acute eGFR dip, and this was again consistent in the other subgroups. The likelihood of a 40% or greater decrease in eGFR from baseline was reduced by 30%, and the likelihood of development of kidney failure was reduced by 34% with empagliflozin. The annual rate of decline in chronic eGFR slope decreased by 64% with empagliflozin, and this was greater among participants with diabetes (74%) than those without diabetes (42%). The relative decrease in chronic eGFR slope was 81%, 69%, 59%, and 41% less in participants with UACR < 30, 30 to < 300, 300 to < 1000, and 1000 or more, respectively, which the authors consider an argument in favor of starting SGLT2i early rather than waiting for albuminuria to develop. The authors suggest that, although acute increase in creatinine is listed as an adverse effect in

作者利用4项安慰剂对照试验23340名参与者的个体水平数据，EMPA-REG OUTCOME（7020例T2D和既往ASCVD患者）、emperr - reduced和emperr - preserved（9711例心力衰竭患者）和EMPA-KIDNEY（6609例CKD进展风险患者），研究了钠-葡萄糖反转运蛋白2抑制剂（SGLT2i）恩格列净在蛋白尿低、无糖尿病的情况下的益处。在治疗开始时估计急性肾小球滤过率（eGFR）下降较大的患者中，通过将治疗后eGFR和随机化eGFR之间的差异除以两种测量之间的时间来计算治疗后无下降的eGFR斜率，10630（45.5%）参与者在停止研究治疗后测量了治疗后eGFR，其中6250人分配给恩格列净[1]。急性表皮生长因子受体下降较大的独立预测因子包括年龄较大的每十年下降(0.9%),更高的表皮生长因子受体(eGFR≥85 vs . & lt浸大4.6%;37毫升/每分钟1.73平方米)和水平蛋白尿(大2.9%下降为尿白蛋白/肌酐比值(UACR)≥324 vs . & lt; 6毫克/ g),肾素-血管紧张素系统抑制剂和利尿剂使用(使用与不使用较大的下降1.1%和0.8%,分别),较高的收缩压(浸大0.9%每17毫米汞柱),红细胞压积降低（每4.8%下降0.9%），BMI降低（每5.8 kg/m2下降0.5%）。在12031名恩帕列净组和9761名安慰剂组中，分别有2948名（24.5%）和1219名（12.5%）受试者出现了超过14%的4周eGFR下降，其中随机分配到恩帕列净组的受试者中有311名（2.6%）出现急性eGFR下降，而接受安慰剂组的受试者中有154名（1.6%）出现急性eGFR下降。在分配给恩格列净的患者中，随访血清肌酐增加50%或更高的可能性降低了20%，无论急性eGFR下降的预测大小、糖尿病状态、基线eGFR或蛋白尿、既往心力衰竭或基线NT-proBNP。同样，分配恩格列净使急性肾损伤的风险降低了27%，而不管急性eGFR下降的预测大小，这在其他亚组中也是一致的。使用恩格列净，eGFR从基线下降40%或更高的可能性降低了30%，发生肾衰竭的可能性降低了34%。使用恩格列净后，慢性eGFR斜率的年下降率下降了64%，糖尿病患者（74%）比无糖尿病患者（42%）更大。在UACR为30、30 ~ 300、300 ~ 1000和1000以上的患者中，慢性eGFR斜率的相对下降分别为81%、69%、59%和41%，作者认为这是支持早期开始SGLT2i治疗而不是等待蛋白尿发展的一个论据。作者认为，尽管急性肌酐升高在恩格列净和其他SGLT2i的产品标签中被列为不良反应，但分析表明这与不良结果无关，他们“不鼓励开始后常规重新测量eGFR”。在一项对800例微量或大量蛋白尿患者的研究中，芬纳酮和恩帕列净联合使用在减少蛋白尿方面的附加效益比单独使用芬纳酮高29%，比单独使用恩帕列净高32%[10]。在基线时接受或未接受GLP-1RA的患者中，效果相似，这意味着这三种药物，以及影响肾素-血管紧张素-醛固酮系统的药物的使用，可能都可以被认为是互补的，它们的心肾益处bb0。一项类似的分析比较了3533名T2D和CKD患者的随机化效应，在基线时接受矿皮质激素受体拮抗剂（MRA）的257名患者与未接受这种治疗的患者中，semaglutide与安慰剂的随机化期为3.4年。在接受MRA的组中，eGFR较基线或其他肾脏结果降低≥50%的患者为17%，而未随机接受semaglutide的患者为30%，肾脏事件减少49%，而在未接受MRA的患者中，semaglutide的肾脏结果发生率为19%，而未随机接受semaglutide的患者为23%，减少21%。虽然相互作用的测试显示这在统计上不显著，但数字差异显然有利于同时使用西马鲁肽和MRA。基于肌酐或胱抑素C的eGFR平均降低，在接受和未接受MRA的患者中显示出与西马鲁肽相似的保护作用。1060例T2D患者糖尿病酮症酸中毒（DKA）病例的分析，比较sglt2d治疗的267例患者和793例未使用bbb的患者。中位糖尿病持续时间为10年，SGLT2i使用2个月；入院时HbA1c 9.2%，酮5.7，乳酸1.5，碳酸氢盐8.8 mmol/L, pH 7.1，葡萄糖191，肌酐1。 1 mg / dL;平均DKA持续时间48 h。在SGLT2i使用者与非使用者的因果匹配比较中，葡萄糖为360 vs 463， pH为7.1 vs 7.2，乳酸为2.7 vs 3.5，酮为5.5 vs 5.4 mmol/L。低钾血症发生率在SGLT2i使用者和非使用者中分别为49%和39%，住院时间和ICU入院时间相似。总的来说，尽管SGLT2i使用者的血糖水平较低，酸中毒程度较高，但差异不大。最值得注意的是，SGLT2i使用者发生DKA的糖尿病管理不理想，这提示了一种合理的预防方法。成纤维细胞生长因子21 （Fibroblast growth factor 21, FGF21）主要在肝脏合成，增强肝脏胰岛素敏感性，降低肝脏甘油三酯积累，具有抗炎、抗氧化和抗纤维化作用，目前有几种FGF21类似物正在开发中。在一项2期研究中，126名活检证实的脂肪性肝炎和组织学F2或F3期纤维化患者接受FGF21类似物efruxifermin与安慰剂治疗96周，安慰剂组34名参与者中有8名（24%）出现≥1期纤维化改善，未出现MASH恶化，28 mg组26名中有12名（46%），50 mg组28名中有21名。安慰剂组肝脏脂肪减少10%，伊夫昔弗明28和59 mg组分别减少34%和41%，脂联素分别增加17%，28%和63%，有证据表明胰岛素抵抗减少，脂质改善，丙氨酸转氨酶和天冬氨酸转氨酶减少，瞬时弹性成像显示肝脏硬度降低。27名受试者中，有8人接受了50mg埃夫昔弗明治疗，疾病几乎完全逆转。副作用包括腹泻、恶心、呕吐和食欲增加。骨矿物质密度在第48周没有变化，虽然在第96周出现下降，但没有增加骨折。在对154名参与者进行的替西肽代谢反应与肝脏bx证实的MASH改善之间关系的个体参与者分析中，59%的参与者患有T2D， 80名参与者的MASH得到缓解，纤维化没有恶化，其中76人接受了替西肽治疗。有反应者体重减轻了16%，而无反应者体重减轻了7%。应答者的糖化血红蛋白、甘油三酯和肝脂肪降低幅度更大，胰岛素敏感性和脂联素增加幅度更大。纤维化的改善与体重减轻和HbA1c的改善相似。体重减轻与肝脏脂肪、肝脏僵硬和炎症相关。少突胶质细胞（OL）是中枢神经系统中的特化细胞，与星形胶质细胞和小胶质细胞一起支持神经元功能，OL产生髓鞘，髓鞘包括脑白质的很大一部分，参与学习和记忆以及神经元回路重塑；OL高度依赖糖酵解代谢底物，反过来为神经元轴突代谢提供能量[9]。在一项关于OL葡萄糖依赖性胰岛素性多肽受体（GIPR）信号传导作用的研究中，Hansford等人发现，GIPR在OL上高度表达，特别是在中下基底丘脑的中位凸起（ME），这是缺乏血脑屏障的大脑区域，因此直接暴露于循环激素和营养物质中，外周给药标记的GIP受体激动剂导致ME摄取OL。在饮食诱导的肥胖模型中，OL特异性G

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引用次数: 0

Blood Pressure Variability and End-Stage Kidney Disease Among Individuals With Type 2 Diabetes: A Nationwide Cohort Study 2型糖尿病患者血压变异性和终末期肾病：一项全国性队列研究

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-10-23 DOI: 10.1111/1753-0407.70160

Youn Huh, Hae-Rim Kim, Hye Soon Park

Background

Longitudinal evidence of the relationship between blood pressure (BP) variability and end-stage kidney disease (ESKD) among individuals with type 2 diabetes is limited. Therefore, we evaluated the association between BP variability and ESKD in Korean adults with type 2 diabetes.

Methods

The study utilized data from the Korean National Health Insurance Service database, comprising health checkups conducted between 2004 and 2015. We enrolled 36 421 adults aged ≥ 19 years with type 2 diabetes who underwent at least two health checkups and were followed up until the end of 2017. BP variability was measured using the coefficient of variation, standard deviation, and variability independent of the mean. Hazard ratios (HRs) and 95% confidence intervals (CIs) for ESKD were determined using multivariate Cox proportional hazards regression analysis.

Results

During a median follow-up of 8.05 years, 290 patients with ESKD were identified. The highest quartile of systolic or diastolic BP variability presented a higher risk of ESKD than did the lowest quartile of systolic or diastolic BP variability. The group with the highest systolic and diastolic BP variability had a 77% higher risk of ESKD than did those in the lowest three quartiles of both systolic and diastolic BP variability. These associations were present in younger individuals without comorbidities.

Conclusions

Among individuals with type 2 diabetes, increased BP variability was associated with an increased risk of ESKD. These associations were similarly observed in younger individuals without comorbidities. Maintaining a consistent BP seems to be important to prevent progression to ESKD in individuals with type 2 diabetes.

背景：2型糖尿病患者血压（BP）变异性与终末期肾脏疾病（ESKD）之间关系的纵向证据有限。因此，我们评估了韩国成人2型糖尿病患者的血压变异性和ESKD之间的关系。方法：该研究利用了韩国国民健康保险服务数据库的数据，包括2004年至2015年进行的健康检查。我们招募了36421名年龄≥19岁的2型糖尿病患者，他们接受了至少两次健康检查，并随访至2017年底。使用变异系数、标准差和独立于平均值的变异来测量BP变异性。采用多变量Cox比例风险回归分析确定ESKD的风险比（hr）和95%置信区间（CIs）。结果：在中位8.05年的随访期间，确定了290例ESKD患者。收缩压或舒张压变异性最高的四分位数比收缩压或舒张压变异性最低的四分位数表现出更高的ESKD风险。收缩压和舒张压变异性最高的组发生ESKD的风险比收缩压和舒张压变异性最低的组高77%。这些关联存在于没有合并症的年轻个体中。结论：在2型糖尿病患者中，血压变异性增加与ESKD风险增加相关。在没有合并症的年轻个体中也同样观察到这些关联。在2型糖尿病患者中，维持稳定的血压似乎对预防进展为ESKD很重要。

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引用次数: 0

The Impact of Diabetes Mellitus-Related Oxidative Stress on Male Fertility: A Review 糖尿病相关氧化应激对男性生育能力影响的研究进展

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-10-22 DOI: 10.1111/1753-0407.70157

Simon Mwaringa Dena, Adesola Oluwaseun Adeleye, Kutullo Mohlala, Bridget Cebisile Langa, Chinyerum Sylvia Opuwari

Diabetes mellitus (DM) significantly impairs male reproductive health, largely through hyperglycemia-induced oxidative stress (OS). Elevated glucose activates detrimental metabolic pathways, notably the polyol pathway, which depletes antioxidant defenses and generates reactive oxygen species (ROS). This oxidative burden damages spermatozoa, leading to reduced motility, abnormal morphology, DNA fragmentation, and disrupted membrane integrity. OS also compromises the hypothalamic–pituitary–gonadal axis, lowering testosterone synthesis and impairing spermatogenesis. The formation of advanced glycation end products (AGEs) and chronic inflammation further exacerbate Leydig and Sertoli cell dysfunction, microvascular injury, and testicular apoptosis. Clinical evidence consistently links DM to deteriorated semen parameters, hormonal imbalances, and reduced natural conception rates, with poorer outcomes in assisted reproductive technologies. Obesity and metabolic syndrome, common comorbidities in DM, amplify oxidative stress and further impair fertility potential. While seminal plasma contains enzymatic and non-enzymatic antioxidants, these defenses are often insufficient in diabetic men. Targeted interventions, including antioxidant therapy, lifestyle modifications, glycemic control, and management of comorbidities, offer promise in mitigating oxidative damage. This review synthesizes current evidence on the molecular, endocrine, and clinical consequences of DM-related oxidative stress on male fertility, underscoring the need for integrated management strategies to preserve reproductive function in diabetic men.

糖尿病（DM）主要通过高血糖诱导的氧化应激（OS）显著损害男性生殖健康。葡萄糖升高激活有害的代谢途径，特别是多元醇途径，它会消耗抗氧化防御并产生活性氧（ROS）。这种氧化负担损害精子，导致活力降低、形态异常、DNA断裂和膜完整性破坏。OS还损害下丘脑-垂体-性腺轴，降低睾酮合成并损害精子发生。晚期糖基化终产物（AGEs）的形成和慢性炎症进一步加剧了间质和支持细胞功能障碍、微血管损伤和睾丸凋亡。临床证据一致表明，糖尿病与精液参数恶化、激素失衡、自然受孕率降低以及辅助生殖技术的预后较差有关。肥胖和代谢综合征是糖尿病的常见合并症，可放大氧化应激并进一步损害生育潜力。虽然精浆中含有酶促和非酶促抗氧化剂，但糖尿病男性往往缺乏这些防御能力。有针对性的干预措施，包括抗氧化治疗、生活方式改变、血糖控制和合并症的管理，为减轻氧化损伤提供了希望。这篇综述综合了目前dm相关氧化应激对男性生育能力的分子、内分泌和临床影响的证据，强调需要综合管理策略来保护糖尿病男性的生殖功能。

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引用次数: 0

Effects of Intensive Systolic Blood Pressure Control on Kidney Outcomes in Patients With and Without CKD: A Post Hoc Analysis of SPRINT and ACCORD-BP Trials 强化收缩压控制对有和无CKD患者肾脏预后的影响：SPRINT和ACCORD-BP试验的事后分析

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-10-21 DOI: 10.1111/1753-0407.70162

Xiaoli Xu, Xuan Zhao, Yi Ding, Xianglin Wu, Qiuyu Cao, Kan Wang, Yu Xiang, Siyu Wang, Xiaoyun Zhang, Min Xu, Tiange Wang, Zhiyun Zhao, Yuhong Chen, Jieli Lu, Yufang Bi, Mian Li, Yu Xu

Background

The effects of intensive blood pressure (BP) control on adverse kidney outcomes remain undetermined.

Methods

This post hoc analysis included the Systolic Blood Pressure Intervention Trial (SPRINT) participants and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) participants receiving standard glucose-lowering treatment and satisfying SPRINT eligibility criteria. The risks of kidney events between intensive (systolic BP < 120 mmHg) and standard (systolic BP < 140 mmHg) controls in participants with or without baseline chronic kidney disease (CKD) were compared using Cox proportional hazards models.

Results

A total of 10,946 participants (2724 with CKD and 8222 without CKD) were included. During the intervention and post-intervention periods, the risk of renal failure was either reduced by intensive BP control in participants with CKD (HR = 0.46; 95% CI = 0.22–0.97) or was not significantly different between intensive and standard BP control in participants without CKD (HR = 0.88, 95% CI = 0.52–1.49; p_interaction = 0.128). The risk of ≥ 30% reduction in estimated glomerular filtration rate (eGFR) was increased and the risk of albuminuria was decreased by intensive BP control in participants with or without CKD. Intensive BP control increased the risk of CKD progression to moderate- or high-risk category, but not to very-high risk category according to the Kidney Disease Improving Global Outcomes (KDIGO) risk categories.

Conclusions

The intensive BP control might increase the risk of mild CKD progression but not of more advanced CKD progression or renal failure compared with the standard BP control.

背景：强化血压（BP）控制对肾脏不良结局的影响尚不确定。方法：本事后分析纳入收缩压干预试验（SPRINT）参与者和控制糖尿病心血管风险血压行动（ACCORD-BP）参与者，接受标准降糖治疗并满足SPRINT资格标准。结果：共纳入10,946名参与者（2724名CKD患者和8222名非CKD患者）。在干预期间和干预后，CKD患者强化血压控制可降低肾功能衰竭的风险（HR = 0.46; 95% CI = 0.22-0.97），而非CKD患者强化血压控制与标准血压控制之间无显著差异（HR = 0.88, 95% CI = 0.52-1.49； p交互作用= 0.128）。在有或没有CKD的参与者中，通过强化血压控制，估计肾小球滤过率（eGFR）降低≥30%的风险增加，蛋白尿的风险降低。根据肾脏疾病改善全球预后（KDIGO）风险分类，强化血压控制会增加CKD进展到中度或高风险类别的风险，但不会增加到非常高风险类别。结论：与标准血压控制相比，强化血压控制可能会增加轻度CKD进展的风险，但不会增加更晚期CKD进展或肾功能衰竭的风险。

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引用次数: 0

The Association of Insulin Sensitivity, Secretion, and Clearance With Subclinical Atherosclerosis in Middle-Aged Adults Without Diabetes: A Cross-Sectional Analysis of the SCAPIS Cohort 无糖尿病中年人胰岛素敏感性、分泌和清除率与亚临床动脉粥样硬化的关系：SCAPIS队列的横断面分析

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-10-19 DOI: 10.1111/1753-0407.70161

Rebecka Renklint, Per Liv, Ioannis Katsoularis, Tommy Olsson, Julia Otten

Object

Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD), with increased risk already observed in the prediabetic state. This study aimed to investigate the association of insulin sensitivity, secretion, and clearance with subclinical atherosclerosis in a randomly selected cohort of Swedish adults aged 50–64 years without known diabetes.

Material and Methods

For this cross-sectional analysis, data from the Umeå site of the Swedish CArdioPulmonary BioImage Study (SCAPIS) were used, which included 2507 individuals aged 50–64 years. After applying exclusion criteria, 2054 participants remained. Insulin sensitivity, secretion, and clearance were calculated using an oral glucose tolerance test (OGTT). Atherosclerosis was assessed by coronary computed tomography angiography (CCTA) and carotid ultrasound, yielding coronary artery calcification scores (CACS), coronary segment involvement scores (SIS), and total carotid plaque counts. Ordinal regression models analyzed associations between insulin measures and atherosclerosis, adjusting for cardiovascular risk factors.

Results

Lower insulin sensitivity, as measured by the GUTT index, was associated with higher CACS and SIS, but not with carotid plaque count. No significant relationship was found between insulin secretion (Insulinogenic Index) and any atherosclerotic marker. Reduced insulin clearance was associated with CACS and SIS in unadjusted analyses; however, these associations did not persist after multivariable adjustment.

Conclusion

In individuals without diabetes, insulin resistance is associated with markers of subclinical coronary atherosclerosis, reinforcing its role in early CVD. Insulin secretion or clearance are not directly associated with measures of subclinical atherosclerosis in this population but may contribute indirectly via effects on circulating insulin levels.

2型糖尿病（T2D）是心血管疾病（CVD）的危险因素，在糖尿病前期已经观察到风险增加。这项研究旨在调查胰岛素敏感性、分泌和清除与亚临床动脉粥样硬化的关系，研究对象是随机选择的50-64岁无糖尿病的瑞典成年人。材料和方法本横断面分析的数据来自瑞典心肺生物图像研究（SCAPIS），其中包括2507名年龄在50-64岁之间的个体。在应用排除标准后，仍有2054名参与者。使用口服葡萄糖耐量试验（OGTT）计算胰岛素敏感性、分泌和清除率。通过冠状动脉计算机断层血管造影（CCTA）和颈动脉超声评估动脉粥样硬化，得出冠状动脉钙化评分（CACS）、冠状动脉段累及评分（SIS）和总颈动脉斑块计数。顺序回归模型分析了胰岛素测量和动脉粥样硬化之间的关系，调整了心血管危险因素。结果通过GUTT指数测量的胰岛素敏感性较低与较高的CACS和SIS相关，但与颈动脉斑块计数无关。胰岛素分泌（胰岛素生成指数）与任何动脉粥样硬化标志物之间没有明显关系。在未经调整的分析中，胰岛素清除率降低与CACS和SIS相关；然而，这些关联在多变量调整后并没有持续存在。结论在没有糖尿病的个体中，胰岛素抵抗与亚临床冠状动脉粥样硬化标志物相关，加强了其在早期CVD中的作用。胰岛素分泌或清除与亚临床动脉粥样硬化的测量没有直接关系，但可能通过对循环胰岛素水平的影响间接起作用。

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引用次数: 0

Diabetic Kidney Disease-Associated Pathological Angiogenesis: The Role of Aquaporin-1 糖尿病肾病相关病理性血管生成：水通道蛋白-1的作用

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes

Pub Date : 2025-10-17 DOI: 10.1111/1753-0407.70159

Fengyi Zhang, Jiayi Zhang, Xin Wang, Yaxin Chen, Ziyang Cheng, Jingjing Pan, Yufeng Zhang, Yujie Li, Wenbo Wang, Linhua Zhao

Diabetic kidney disease (DKD) is recognized as one of the leading causes of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide, representing a rapidly growing global public health concern. Despite significant advances in understanding the complex pathophysiological mechanisms of DKD, curative treatments are currently unavailable, and the reversal of established renal injury remains an elusive goal in clinical practice. Among various pathological features, aberrant angiogenesis has been closely associated with glomerular injury and the early development of proteinuria in DKD, playing a crucial role in driving disease progression. However, the molecular mechanisms underlying this pathological angiogenesis in DKD remain incompletely understood and warrant further elucidation. Recent research has increasingly implicated aquaporins (AQPs), a family of transmembrane water channel proteins, in the pathogenesis of both acute and chronic kidney disorders, including DKD. In particular, aquaporin-1 (AQP1), which is highly expressed in renal tissues, has emerged as a potential modulator of angiogenic activity within the kidney microenvironment. Although AQP1 and aberrant angiogenesis have been individually explored in the context of DKD, no comprehensive review has systematically examined their interrelationship. This review consolidates current evidence regarding the role of AQP1 in pathological angiogenesis during DKD progression, highlighting its potential significance and identifying gaps that warrant further investigation.

糖尿病肾病（DKD）是全球公认的慢性肾脏疾病（CKD）和终末期肾脏疾病（ESKD）的主要原因之一，是一个快速增长的全球公共卫生问题。尽管在理解DKD复杂的病理生理机制方面取得了重大进展，但目前尚无根治性治疗方法，并且在临床实践中逆转已建立的肾损伤仍然是一个难以捉摸的目标。在多种病理特征中，血管生成异常与肾小球损伤和蛋白尿的早期发展密切相关，在推动疾病进展中起着至关重要的作用。然而，DKD病理性血管生成的分子机制仍然不完全清楚，需要进一步阐明。最近的研究越来越多地涉及水通道蛋白（AQPs），一个跨膜水通道蛋白家族，在急性和慢性肾脏疾病，包括DKD的发病机制中。特别是在肾组织中高度表达的水通道蛋白-1 (AQP1)，已经成为肾脏微环境中血管生成活性的潜在调节剂。虽然AQP1和异常血管生成已经在DKD的背景下单独探讨，但没有全面的综述系统地研究它们之间的相互关系。这篇综述巩固了目前关于AQP1在DKD进展过程中病理性血管生成中的作用的证据，强调了其潜在的重要性，并确定了值得进一步研究的空白。

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引用次数: 0