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Androgenic Steroid Hormones and Endurance Exercise in Athletic Women. 雄性类固醇激素与运动女性的耐力锻炼
Pub Date : 2024-09-01 Epub Date: 2024-07-02 DOI: 10.3390/endocrines5030018
Anthony C Hackney, Raul Cosme Ramos Prado, Eimear Dolan

This study investigated the impact of intensive endurance exercise on circulating androgenic steroid hormones in women. Fifteen normally menstruating athletic women participated. They completed intensive endurance exercise (treadmill running) until volitional fatigue in their follicular phase, with blood samples collected at pre-exercise, volitional fatigue, 90 min and 24 h into recovery. The steroid hormones (total, free testosterone, dehydroepiandrosterone [DHEA], and DHEA-sulfate [DHEA-S], cortisol) were analyzed in blood sera. Non-parametric statistics were used to assess changes across exercise and recovery. At volitional fatigue, all hormones, except free testosterone, were significantly (p < 0.05) increased compared to pre-exercise levels. Most hormones remained elevated through 90 min of recovery, with DHEA, DHEA-S, and total testosterone changes being significant (p < 0.05). At 24 h of recovery, hormonal levels were reduced; specifically, DHEA, DHEA-S, and total testosterone compared to baseline (p < 0.01 to 0.06). Increases in cortisol levels at volitional fatigue and 90 min of recovery were correlated with reductions in total testosterone, DHEA, and DHEA-S observed at 24 h of recovery (rho > -0.62, p < 0.05). In conclusion, in menstruating women performing intensive endurance exercise during their follicular phase, their androgenic steroid hormones remain elevated during early recovery but are suppressed at 24 h of recovery. The latter finding indicates that establishing a resting endocrine equilibrium requires a longer recovery period than 24 h.

这项研究调查了高强度耐力运动对女性体内循环雄性类固醇激素的影响。15 名月经正常的运动女性参加了这项研究。她们在卵泡期完成高强度耐力运动(跑步机跑步)直至自愿疲劳,并在运动前、自愿疲劳、90 分钟和恢复后 24 小时采集血液样本。对血清中的类固醇激素(总睾酮、游离睾酮、脱氢表雄酮 [DHEA]、DHEA-硫酸盐 [DHEA-S]、皮质醇)进行分析。非参数统计用于评估运动和恢复期间的变化。与运动前水平相比,在自愿疲劳时,除游离睾酮外,所有激素均显著升高(p < 0.05)。大多数激素在 90 分钟的恢复期内保持升高,其中 DHEA、DHEA-S 和总睾酮变化显著(p < 0.05)。恢复 24 小时后,激素水平有所降低,特别是 DHEA、DHEA-S 和总睾酮与基线相比有所降低(p < 0.01 至 0.06)。在自愿疲劳和恢复 90 分钟时,皮质醇水平的增加与恢复 24 小时后观察到的总睾酮、DHEA 和 DHEA-S 的减少相关(rho > -0.62,p <0.05)。总之,月经期妇女在卵泡期进行高强度耐力锻炼时,其雄性类固醇激素在恢复早期会保持升高,但在恢复 24 小时后会受到抑制。后一项发现表明,建立静息内分泌平衡需要比 24 小时更长的恢复期。
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引用次数: 0
Isolated Growth Hormone Deficiency 孤立的生长激素缺乏症
Pub Date : 2024-08-08 DOI: 10.3390/endocrines5030025
A. Ibba, C. Guzzetti, Lavinia Sanfilippo, Sandro Loche
Growth hormone deficiency (GHD) is the most frequent pituitary hormone deficiency in childhood, with an incidence of 1 in 4000–10,000 live births. GHD can be congenital (genetic or due to hypothalamic/pituitary abnormalities) or acquired and can be isolated (IGHD) or associated with other pituitary hormone deficiencies, but most cases are idiopathic. GH stimulation testing is commonly used in the diagnostic workup of GHD, except for some clinical conditions that do not require GH stimulation tests for the diagnosis. Children with GHD receive replacement therapy with daily injections of recombinant human GH (rhGH). RhGH therapy is effective in increasing short-term height gain and adult height in patients with GHD. The safety of long term GH therapy has been confirmed in many large international studies. Recently, long-acting weekly GH formulations have been introduced, showing good efficacy and safety profiles.
生长激素缺乏症(GHD)是儿童时期最常见的垂体激素缺乏症,发病率为每4000-10000名活产婴儿中就有1例。生长激素缺乏症可以是先天性的(遗传或下丘脑/垂体异常所致),也可以是后天获得的,可以是孤立的(IGHD),也可以与其他垂体激素缺乏症伴发,但大多数病例是特发性的。GH 刺激试验通常用于 GHD 的诊断工作,但某些临床病症无需进行 GH 刺激试验即可确诊。GHD患儿接受每日注射重组人GH(rhGH)的替代治疗。RhGH 疗法能有效提高 GHD 患者的短期身高增长和成年身高。许多大型国际研究都证实了长期 GH 治疗的安全性。最近,长效每周 GH 制剂问世,显示出良好的疗效和安全性。
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引用次数: 0
Bitter Phytochemicals Acutely Lower Blood Glucose Levels by Inhibition of Glucose Absorption in the Gut 苦味植物化学物质通过抑制肠道对葡萄糖的吸收来降低血糖水平
Pub Date : 2024-07-25 DOI: 10.3390/endocrines5030022
Kimberly Marie Palatini Jackson, Reham Mhawish, S. Komarnytsky
For early hominids, frequent encounters with plant foods necessitated the ability to discern bitter poisons and adjust the activity of the gastrointestinal system in anticipation of carbohydrate-rich meals. Plants bitters were also used historically to manage a variety of metabolic and digestive disorders despite an immense structural diversity of bitter phytochemicals without a common molecular target. Our study confirms these observations in a standardized C57BL/6J prediabetic mouse model using 24 model compounds by demonstrating acute lower peak blood glucose values and improved glucose tolerance following intragastric, but not intraperitoneal, treatment. The administration of the synthetic bitter compound denatonium benzoate yielded similar results that were attenuated by co-application of the allosteric inhibitor of the bitter TAS2R receptors. We also show that these effects occur dose-dependently; associate with reduced glucose uptake, increased intracellular [Ca2+] fluxes, and enhanced GLP-1 expression; and are attenuated by the TAS2R inhibitor in the neuroendocrine STC-1 intestinal cells. These findings support the view that inhibition of glucose transport from the intestinal lumen to the blood by TAS2R bitter receptor signaling in the gut may represent a common mechanism in the acute response to oral ingestion of bitter phytochemicals.
对于早期类人猿来说,由于经常接触植物性食物,因此必须具备辨别苦味毒物的能力,并在进食富含碳水化合物的食物时调整肠胃系统的活动。尽管苦味植物化学物质的结构种类繁多,却没有一个共同的分子靶标,但历史上人们还是用苦味植物来控制各种代谢和消化紊乱。我们的研究证实了在使用 24 种模型化合物的标准化 C57BL/6J 糖尿病前期小鼠模型中的上述观察结果,结果表明,经胃内而非腹腔治疗后,血糖峰值急剧下降,葡萄糖耐量得到改善。服用合成苦味化合物苯甲酸地那铵也会产生类似的结果,而同时服用苦味 TAS2R 受体的异构抑制剂则会减弱这种结果。我们还发现,这些效应的发生与剂量有关,与葡萄糖摄取减少、细胞内[Ca2+]通量增加和 GLP-1 表达增强有关,并在神经内分泌 STC-1 肠细胞中被 TAS2R 抑制剂减弱。这些发现支持这样一种观点,即肠道中的 TAS2R 苦味受体信号抑制葡萄糖从肠腔向血液的转运可能代表了口服苦味植物化学物质后急性反应的一种共同机制。
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引用次数: 0
Differences in Exercise-Linked Biomarkers between Premenopausal and Postmenopausal Middle-Aged Females 绝经前和绝经后中年女性运动相关生物标志物的差异
Pub Date : 2024-07-23 DOI: 10.3390/endocrines5030021
Anthony J. Giannopoulos, Ahmad Mohammad, M. I. Retsidou, J. Tucker, D. Bornath, Seth F. McCarthy, Rek MacPherson, Tom J. Hazell, P. Klentrou
While the exercise-induced responses of circulated biomarkers related to inflammation and brain health are well documented in humans, little is known about the effect of menopausal status on these responses. This study compared the responses of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) to high-intensity exercise between pre- and postmenopausal middle-aged females. Eight premenopausal (44 ± 3 years) and seven postmenopausal (57 ± 2 years) females performed a high-intensity interval training (HIIT) session consisting of 10 × 1 min running intervals (90% maximum heart rate) separated by 1 min passive recovery intervals. Blood samples were collected at baseline (fasted), pre-exercise (postprandial), and at 0, 30, and 90 min post-HIIT and analyzed for interleukin (IL-6) and 10 (IL-10), tumour necrosis factor-alpha (TNF-α), and BDNF. IL-6 significantly increased from pre-exercise to 0 min post-HIIT in postmenopausal (+40%, p = 0.01) and to 30 min post-HIIT in premenopausal females (+60%, p = 0.02). IL-6 remained elevated at 90 min post-HIIT in premenopausal (+104%, p = 0.05) and to a higher degree in postmenopausal females (+385%, p < 0.001). IL-10 showed no response. TNF-α increased from pre- to 0 min post-HIIT (+10%, p = 0.05), then decreased to below pre-exercise at 30 min (−10%, p = 0.02) and 90 min (−5%, p = 0.04) in both groups. BDNF increased immediately post-HIIT in premenopausal (+60%, p < 0.001) but not postmenopausal females. The differences in IL-6 and BDNF responses to HIIT between pre- and postmenopausal females provide evidence of the role of female reproductive hormones in the regulation of these exercise-induced responses.
虽然运动诱导的与炎症和大脑健康相关的循环生物标志物的反应在人类中已有大量记载,但人们对绝经状态对这些反应的影响知之甚少。本研究比较了绝经前和绝经后中年女性的炎症细胞因子和脑源性神经营养因子(BDNF)对高强度运动的反应。8 名绝经前(44 ± 3 岁)和 7 名绝经后(57 ± 2 岁)女性进行了高强度间歇训练(HIIT),包括 10 × 1 分钟的跑步间歇(90% 最大心率)和 1 分钟的被动恢复间歇。在基线(空腹)、运动前(餐后)、HIIT 后 0 分钟、30 分钟和 90 分钟收集血液样本,分析白细胞介素(IL-6)和 10(IL-10)、肿瘤坏死因子-α(TNF-α)和 BDNF。绝经后女性的 IL-6 从运动前到 HIIT 后 0 分钟明显升高(+40%,p = 0.01),绝经前女性的 IL-6 从运动前到 HIIT 后 30 分钟明显升高(+60%,p = 0.02)。绝经前(+104%,p = 0.05)和绝经后女性(+385%,p < 0.001)在 HIIT 后 90 分钟内 IL-6 仍保持升高。IL-10 无反应。TNF-α 在 HIIT 后 0 分钟内从运动前上升(+10%,p = 0.05),然后在 30 分钟(-10%,p = 0.02)和 90 分钟(-5%,p = 0.04)时下降到运动前的水平。在绝经前(+60%,p < 0.001)而非绝经后的女性中,BDNF在HIIT后立即增加(+60%,p < 0.001)。绝经前和绝经后女性对 HIIT 的 IL-6 和 BDNF 反应的差异证明了女性生殖激素在调节这些运动诱导反应中的作用。
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引用次数: 0
Beverage Consumption Patterns and Their Association with Metabolic Health in Adults from Families at High Risk for Type 2 Diabetes in Europe—The Feel4Diabetes Study 欧洲 2 型糖尿病高风险家庭成人的饮料消费模式及其与代谢健康的关系--Feel4Diabetes 研究
Pub Date : 2024-07-22 DOI: 10.3390/endocrines5030020
Paris Kantaras, Niki Mourouti, T. Mouratidou, Ekaterini Chatzaki, M. Karaglani, V. Iotova, N. Usheva, I. Rurik, P. Torzsa, Luis A. Moreno, S. Liatis, K. Makrilakis, Yannis Manios
In total, 3274 adults (65.2% females) from six European countries were included in this cross-sectional analysis using data from the baseline assessment of the Feel4Diabetes study. Anthropometric, sociodemographic, dietary and behavioral data were assessed, and the existence of metabolic syndrome (MetS) was recorded. Beverage consumption patterns (BCPs) were derived via principal component analysis. Three BCPs were derived explaining 39.5% of the total variation. BCP1 was labeled as “Alcoholic beverage pattern”, which loaded heavily on high consumption of beer/cider, wine and other spirits; BCP2 was labeled as “High in sugars beverage pattern” that was mainly characterized by high consumption of soft drinks with sugar, juice containing sugar and low consumption of water; and BCP3 was labeled as “Healthy beverage pattern” that was mainly characterized by high consumption of water, tea, fruit juice freshly squeezed or prepacked without sugar and low consumption of soft drinks without sugar. After adjusting for various confounders, BCP2 was positively associated with elevated triglycerides (p = 0.001), elevated blood pressure (p = 0.001) elevated fasting glucose (p = 0.008) and the existence of MetS (p = 0.006), while BCP1 was inversely associated with reduced HDL-C (p = 0.005) and BCP3 was inversely associated with elevated blood pressure (p = 0.047). The establishment of policy actions as well as public health nutritional education can contribute to the promotion of a healthy beverage consumption.
这项横断面分析共纳入了来自六个欧洲国家的 3274 名成年人(65.2% 为女性),使用的数据来自 Feel4Diabetes 研究的基线评估。对人体测量、社会人口、饮食和行为数据进行了评估,并记录了是否存在代谢综合征(MetS)。通过主成分分析得出了饮料消费模式(BCPs)。得出的三种 BCP 可解释总变异的 39.5%。BCP1 被标记为 "酒精饮料模式",其主要特征是大量饮用啤酒/苹果酒、葡萄酒和其他烈性酒;BCP2 被标记为 "高糖饮料模式",其主要特征是大量饮用含糖软饮料和含糖果汁,而少量饮用水;BCP3 被标记为 "健康饮料模式",其主要特征是大量饮用水、茶、鲜榨果汁或预包装无糖果汁,而少量饮用无糖软饮料。调整各种混杂因素后,BCP2 与甘油三酯升高(p = 0.001)、血压升高(p = 0.001)、空腹血糖升高(p = 0.008)和 MetS 存在(p = 0.006)呈正相关,而 BCP1 与高密度脂蛋白胆固醇降低(p = 0.005)呈反相关,BCP3 与血压升高(p = 0.047)呈反相关。制定政策行动和开展公共卫生营养教育有助于促进健康饮料的消费。
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引用次数: 0
Human and Murine Cell Lines for Adrenocortical Carcinoma and Pheochromocytoma 肾上腺皮质癌和嗜铬细胞瘤的人类和小鼠细胞系
Pub Date : 2024-07-05 DOI: 10.3390/endocrines5030019
Edlira Luca, A. Abate, Katharina Wang, Stefan R. Bornstein, Sandra Sigala, Felix Beuschlein, Svenja Nölting, C. Hantel
Adrenocortical carcinoma (ACC) and pheochromocytoma (PCC) are malignancies originating from distinct layers of the adrenal gland. ACCs arise from the adrenal cortex, are often detected at advanced stages and are associated with poor prognosis. PCCs are mostly benign, arise from the adrenal medulla and have a variable prognosis, with 10% of PCCs resulting in metastasis. Genetic background strongly influences metastasis of PCCs, and no reliable biomarkers that predict metastatic behavior exist to date. Current therapeutic strategies for both ACCs and PCCs are overall limited. Thus, novel preclinical models and drug screening approaches need to be established to aid in the identification of more promising drugs and treatment schemes. In this review, we summarize the currently available human and murine cell lines for both tumor entities.
肾上腺皮质癌(ACC)和嗜铬细胞瘤(PCC)是源自肾上腺不同层次的恶性肿瘤。ACC 来自肾上腺皮质,通常在晚期才被发现,预后较差。PCC多为良性,起源于肾上腺髓质,预后不一,10%的PCC会导致转移。遗传背景对 PCC 的转移有很大影响,迄今为止还没有可靠的生物标志物来预测转移行为。目前针对 ACC 和 PCC 的治疗策略总体上都很有限。因此,需要建立新的临床前模型和药物筛选方法,以帮助确定更有前景的药物和治疗方案。在这篇综述中,我们总结了这两种肿瘤实体目前可用的人类和鼠类细胞系。
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引用次数: 0
A Retrospective Analysis of the Outcomes of Pregnancies in Women Affected by Overt Diabetes Compared to Women Affected by Pre-Existing Type 2 Diabetes 对受显性糖尿病影响的妇女与受原有 2 型糖尿病影响的妇女的妊娠结果进行回顾性分析
Pub Date : 2024-06-11 DOI: 10.3390/endocrines5020017
M. Dalfrà, S. Burlina, Maria Giulia Fioretti, Annunziata Lapolla
Background: Pregestational diabetes mellitus, if not well controlled, determines maternal and fetal complications. According to the new diagnostic criteria for gestational diabetes, the diagnosis of diabetes mellitus can also occur in early pregnancy (overt diabetes). Aim: This study aims to determine pregnancy outcomes in women with overt diabetes compared to women with pre-existing type 2 diabetes. Methods: In this retrospective study, we selected women with pre-existing type 2 and overt diabetes who had at least one pregnancy in the 2010–2022 period at the Diabetic Care Unit of Padova. Results: We analyzed 83 pregnancies, and overt diabetes was diagnosed in 18 pregnancies. In total, 95.5% of patients with overt diabetes and 48% of T2DM patients were immigrants (p < 0.143). No patients with overt diabetes planned their pregnancy, while pregnancy was planned in 26.3% of patients with pre-exiting type 2 diabetes (p < 0.05). Periconception and first-trimester glycemic control were the worst in patients with overt diabetes (HbA1c 9.7 ± 3.1% vs. 7.3% ± 2.3%, p < 0.044, at first visit; 8.1 ± 1.9% and 7.0 ± 1.6%, p < 0.037 in the first trimester) with respect to patients with pre-existing type 2 diabetes. As for maternal outcomes, 16.6% of pregnancies ended in miscarriage, and 5.5% of women developed gestational hypertension; as for newborn outcomes, 16.6% of newborns were LGA, and 11.1% were affected by congenital anomalies without any significant difference with respect to women with pre-existing type 2 diabetes. The high rate of congenital malformations in pregnancies of women with overt diabetes is probably a result of the poor, metabolic control observed during the periconception period when the organogenesis of the fetus takes place. Conclusions: It is essential to utilize procedures for diabetes screening in women of childbearing age not only at the beginning of the pregnancy, but also during the preconception phase or the postmenarcheal period when strong risk factors for diabetes onset are present, such as a high BMI, glycemic disorders, and those who fall under high-risk ethnicity categories.
背景:妊娠期糖尿病如果控制不好,会导致母体和胎儿并发症。根据新的妊娠糖尿病诊断标准,妊娠早期也可诊断为糖尿病(显性糖尿病)。目的:本研究旨在确定明显糖尿病妇女与原有 2 型糖尿病妇女的妊娠结局。研究方法在这项回顾性研究中,我们选取了帕多瓦糖尿病护理中心在 2010-2022 年期间至少有一次妊娠的 2 型糖尿病患者和显性糖尿病患者。研究结果我们对 83 例妊娠进行了分析,其中 18 例妊娠确诊为显性糖尿病。共有 95.5% 的显性糖尿病患者和 48% 的 T2DM 患者是移民(P < 0.143)。没有明显糖尿病患者计划怀孕,而 26.3% 的前期 2 型糖尿病患者计划怀孕(p < 0.05)。与原有 2 型糖尿病患者相比,明显糖尿病患者的围孕期和妊娠头三个月血糖控制最差(首次就诊时 HbA1c 为 9.7 ± 3.1% 对 7.3% ± 2.3%,p < 0.044;妊娠头三个月分别为 8.1 ± 1.9% 和 7.0 ± 1.6%,p < 0.037)。在孕产妇结局方面,16.6%的孕妇流产,5.5%的孕妇罹患妊娠高血压;在新生儿结局方面,16.6%的新生儿为LGA,11.1%的新生儿患有先天性畸形,与已患有2型糖尿病的孕妇相比没有显著差异。患有显性糖尿病的孕妇先天性畸形发生率高,这可能是由于围孕期胎儿器官发育期间代谢控制不佳所致。结论:育龄妇女不仅要在怀孕初期进行糖尿病筛查,而且要在孕前阶段或月经后阶段进行糖尿病筛查,因为此时存在糖尿病发病的高危因素,如高体重指数、血糖紊乱以及属于高危种族的妇女。
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引用次数: 0
Resveratrol Effects on Metabolic Syndrome Features: A Systematic Review and Meta-Analysis 白藜芦醇对代谢综合征特征的影响:系统回顾和元分析
Pub Date : 2024-05-22 DOI: 10.3390/endocrines5020016
Gislaine C. Batista-Jorge, Antônio S. Barcala-Jorge, Deborah F. Lelis, Daniel E. Santos, Antônio H. Jorge, Renato S. Monteiro-Junior, Sérgio H. S. Santos
Resveratrol is a natural polyphenol with important anti-inflammatory and antioxidant properties for treating cardiometabolic disorders. Therefore, the present meta-analysis aimed to review and investigate the oral resveratrol supplementation effects on metabolic syndrome (MetS) components. The bibliographic search was carried out in 2023 in the following databases: PubMed, Web of Science, and Scopus. Studies that investigated the oral resveratrol effects on the MetS parameters were included. Statistical analyses were performed using RevMan Software V.5.3. The main findings showed that resveratrol significantly decreased systolic and diastolic blood pressure while having no significant effects on waist circumference and high-density lipoprotein levels. In addition, glucose level was significantly decreased in the subgroup of studies reporting change from baseline means, although the overall effect was not statistically significant (p = 0.81), while triglyceride levels were increased after the treatment period. In conclusion, the present meta-analysis evidenced the potential therapeutic effect of resveratrol on improving some MetS features, especially regarding systolic blood pressure, diastolic blood pressure, and glucose reduction; however, the results are still borderline and sometimes controversial, which might be justified by the methodological and statistical heterogeneity of the studies, with the latter varying from 17 to 57%.
白藜芦醇是一种天然多酚,具有重要的抗炎和抗氧化作用,可用于治疗心脏代谢疾病。因此,本荟萃分析旨在回顾和研究口服白藜芦醇补充剂对代谢综合征(MetS)成分的影响。文献检索于 2023 年在以下数据库中进行:PubMed、Web of Science 和 Scopus。纳入了调查口服白藜芦醇对代谢综合征参数影响的研究。统计分析使用 RevMan 软件 V.5.3 进行。主要结果显示,白藜芦醇能显著降低收缩压和舒张压,而对腰围和高密度脂蛋白水平没有明显影响。此外,在报告与基线平均值相比变化的研究子组中,血糖水平明显下降,但总体效果无统计学意义(p = 0.81),而甘油三酯水平在治疗期后有所上升。总之,本荟萃分析证明了白藜芦醇对改善某些 MetS 特征的潜在治疗效果,尤其是在收缩压、舒张压和血糖降低方面;然而,研究结果仍不尽相同,有时还存在争议,其原因可能是研究的方法学和统计学异质性,后者从 17% 到 57% 不等。
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引用次数: 0
Which Diabetes Patients Will Benefit the Most from Once-Weekly Basal Insulin Analogs? A Review with a Special Focus on Type 1 Diabetes Patients 哪些糖尿病患者将从每周一次的基础胰岛素类似物中获益最多?特别关注 1 型糖尿病患者的综述
Pub Date : 2024-05-09 DOI: 10.3390/endocrines5020015
Chrysoula Kosmeri, Maria S Baltogianni, V. Giapros, E. Siomou, V. Tsinopoulou, Foteini Balomenou, Anastasios Serbis
Basal insulin analogs, typically administered once or twice daily, have been one of the two pillars of the multiple daily injection (MDI) insulin therapy of patients with type 1 diabetes (T1D) for the last twenty years. Recently, once-weekly basal insulin analogs have been developed and are in late-phase clinical trials. One of these analogs is insulin icodec (icodec), appropriately developed to bind reversibly to albumin and to be gradually released into the patient’s circulation. Icodec has been tried mostly in clinical trials of adult patients with type 2 diabetes. A recent phase 3a clinical trial comprising adult patients with T1D was designed to evaluate icodec’s efficacy and safety compared with a daily basal insulin analog (degludec) after a 26-week main phase plus a safety extension of another 26 weeks. Icodec showed non-inferiority to once-daily degludec in glycated hemoglobin (HbA1c) reduction at week 26, and no significant differences in time in range (TIR) (70–180 mg/dL) and in time above range (TAR) (>180 mg/dL). On the other hand, it was associated with increased rates of clinically significant hypoglycemia (blood glucose < 54 mg/dL) and severe hypoglycemia (external assistance need for recovery), remaining either below or close to the internationally recommended targets for hypoglycemia. Another once-weekly insulin analog, basal insulin Fc (BIF), has been investigated in a phase 2 clinical trial comprising adult patients with T1D, with equally promising results. These preliminary data suggest that once-weekly insulin analogs could be of use for some patients with T1D, for example, patients not taking insulin regularly or those who are on MDI and wish for fewer injections. In addition, due to its prolonged mode of action, it could decrease the risk of diabetic ketoacidosis and the need for hospitalization. Additionally, patients with T1D that struggle with wearing diabetes mellitus devices/closed-loop insulin pumps either due to the cost or due to skin issues may also benefit from long-acting insulin. There is increasing evidence of the benefits of adjunctive therapies to insulin in T1D patients, but these therapies are not FDA-approved due to a possible higher risk of diabetic ketoacidosis. These long-acting insulin analogues could be used with adjunctive therapies in selected patients. This review aims to present available data on the mode of action, clinical trial results, and possible benefits of once-weekly insulin analogs for patients with T1D. In addition, it intends to suggest a future research framework for important clinical questions, such as once-weekly insulin analog use and exercise, sick days, or surgery, that will enhance our knowledge regarding this indisputable innovation in insulin management.
基础胰岛素类似物通常每天给药一次或两次,在过去二十年中一直是每天多次注射(MDI)胰岛素治疗 1 型糖尿病(T1D)患者的两大支柱之一。最近,每周一次的基础胰岛素类似物已经开发出来,并已进入后期临床试验阶段。其中一种类似物是胰岛素 icodec(icodec),这种胰岛素可与白蛋白可逆结合,并逐渐释放到患者的血液循环中。Icodec 主要在 2 型糖尿病成年患者的临床试验中试用。最近的一项 3a 期临床试验由成年 T1D 患者参加,旨在评估 Icodec 与一种日用基础胰岛素类似物(degludec)相比的疗效和安全性。第26周时,Icodec的糖化血红蛋白(HbA1c)降低率与每日一次的degludec相比没有劣势,在范围内时间(TIR)(70-180 mg/dL)和超过范围时间(TAR)(>180 mg/dL)方面也没有显著差异。另一方面,它与临床显著低血糖(血糖< 54 mg/dL)和严重低血糖(需要外部协助恢复)的发生率增加有关,但仍低于或接近国际推荐的低血糖目标值。另一种每周一次的胰岛素类似物--基础胰岛素 Fc(BIF)已在一项由 T1D 成年患者参加的 2 期临床试验中进行了研究,结果同样令人鼓舞。这些初步数据表明,一周一次的胰岛素类似物可用于某些 T1D 患者,例如,不定期使用胰岛素的患者或使用 MDI 但希望减少注射次数的患者。此外,由于胰岛素类似物的作用时间较长,它可以降低糖尿病酮症酸中毒的风险和住院治疗的需要。此外,因费用或皮肤问题而难以佩戴糖尿病设备/闭环胰岛素泵的 T1D 患者也可能从长效胰岛素中获益。越来越多的证据表明,胰岛素辅助疗法对 T1D 患者有益,但由于可能会增加糖尿病酮症酸中毒的风险,这些疗法尚未获得 FDA 批准。这些长效胰岛素类似物可与辅助疗法一起用于部分患者。本综述旨在介绍有关单周胰岛素类似物的作用模式、临床试验结果以及对 T1D 患者可能带来的益处的现有数据。此外,它还打算就一些重要的临床问题提出未来的研究框架,如一周一次的胰岛素类似物的使用与运动、病假或手术,以增进我们对这一胰岛素管理领域无可争议的创新的了解。
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引用次数: 0
Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study 青少年和青年 1 型或 2 型糖尿病患者的神经变性和阿尔茨海默病神经病理学生物标志物:概念验证研究
Pub Date : 2024-05-06 DOI: 10.3390/endocrines5020014
Allison L. B. Shapiro, Christina Coughlan, Brianne M. Bettcher, Meghan E. Pauley, Jeongchul Kim, Petter Bjornstad, Benjamin Rajic, Jennifer Truong, Christopher Bell, Y. Choi, Keenan A. Walker, Huntington Potter, A. Liese, Dana Dabelea, Christopher T. Whitlow
Adult-onset diabetes increases one’s risk of neurodegenerative disease including Alzheimer’s disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.
成年糖尿病会增加罹患包括阿尔茨海默病(AD)在内的神经退行性疾病的风险;然而,与青年糖尿病(Y-DM)相关的风险仍未得到充分探索。我们对 SEARCH 队列中青春期和青年期 Y-DM 患者(1 型,n = 25;2 型,n = 25;59% 女性;青春期,年龄 = 15 岁/o [2。6];成年期,年龄 = 27.4 岁/o [2.2]),并与对照组(青春期,n = 25,年龄 = 14.8 岁/o [2.7];成年期,n = 21,年龄 = 24.9 岁/o [2.8])进行比较。血浆生物标志物包括胶质纤维酸性蛋白(GFAP)、神经丝蛋白轻链(NfL)、磷酸化 tau-181 (pTau181)和淀粉样 beta(Aβ40、Aβ42),均通过 Simoa 进行测量。一部分参与者(n = 7;年龄 = 27.5 岁/o [5.7])和六名对照组(年龄 = 25.1 岁/o [4.5])接受了 PET 扫描,以量化注意力缺失症敏感脑区的脑淀粉样蛋白和 tau 密度。与对照组相比,Y-DM 青少年的血浆 Aβ40、Aβ42 和 GFAP 水平较低,pTau181 水平较高(p < 0.05),这种模式一直持续到成年(p < 0.001)。所有生物标志物均显示,Y-DM 患者从青春期到成年期均有显著增加(p < 0.01),但 Y-DM 患者成年后的脑淀粉样蛋白或 tau 蛋白与对照组无显著差异。初步证据表明,Y-DM 患者中存在临床前注意力缺失症神经病理学,这表明他们罹患神经退行性疾病的风险可能会增加。
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