2型糖尿病早期应用利拉鲁肽的益处

随着2型糖尿病的病程进展,临床医生会面临越来越多的挑战,传统的降糖药物不能满足2型糖尿病复杂的治疗需求.胰升糖素样肽1( GLP-1)具有多重生理作用,可以满足糖尿病治疗的多方面需求.研究显示人GLP-1类似物——利拉鲁肽在2型糖尿病患者早期应用可有效控制血糖,同时保护β细胞、减低体重,并降低肥胖患者糖尿病前期的患病率,带来多重获益.本文就利拉鲁肽早期应用的临床益处作综述.     

利拉鲁肽对胰岛β细胞保护作用的研究进展

胰岛β细胞衰竭是糖尿病致病机制的核心,也是治疗2型糖尿病的关键靶点.已有众多基础及临床研究证实胰升糖素样肽1及其类似物利拉鲁肽具有葡萄糖依赖性降糖作用.同时,还具有显著改善胰岛β细胞功能的作用,为2型糖尿病的治疗提供了新的选择.     

艾塞那肽的作用机制及临床疗效

作为胰高血糖素样肽-1(GLP-1)的受体激动剂,艾塞那肽具有促进葡萄糖依赖的胰岛素分泌、抑制胰高血糖素分泌、增加胰岛素敏感性、延缓胃排空、降低食欲及食物摄人等作用.临床研究显示,艾塞那肽可显著降低2型糖尿病患者糖化血红蛋白( Hb) A1c、空腹血糖、餐后血糖水平并减轻患者体重,且对2型糖尿病心血管并发症有益.基于其独特的降糖模式,艾塞那肽已成为2型糖尿病治疗的新靶点.     

司美格鲁肽的临床应用研究进展

司美格鲁肽是一种新型的长效胰高糖素样肽-1受体激动剂(GLP-1RA), 和传统的GLP-1RA比较, 半衰期延长至7 d。笔者就分子结构和作用机制、降糖、心血管保护作用、减重、肾脏保护作用、在非酒精性脂肪肝病和神经退行性疾病中的治疗进展进行综述。除了降糖、减重作用显著外, 司美格鲁肽还可从多方面实现对心脑血管的保护, 包括保护血管内皮、降低血压、改善血脂、减轻炎症、改善微循环等, 且耐受性良好。同时, 司美格鲁肽还能降低2型糖尿病患者的白蛋白尿、保护肾脏、降低肾脏复合终点事件发生风险, 可用于糖尿病肾脏病的防治。司美格鲁肽还具有改善肝脏和大脑中的胰岛素抵抗, 发挥保护肝脏、减少肝脏中的脂肪含量以及提高认知能力、保护神经的作用, 亦是非酒精性脂肪性肝病和神经退行性疾病的治疗选择。     

司美格鲁肽治疗2型糖尿病合并动脉硬化性心血管疾病1例

回顾性分析1例在贵州省黔东南州人民医院内分泌代谢科治疗, 长期血糖控制不佳合并动脉硬化性心血管疾病(ASCVD)的2型糖尿病(T2DM)患者, 使用司美格鲁肽优化降糖方案有效控制血糖的诊疗过程并进行文献复习。患者为59岁男性, 因"发现血糖升高10余年, 血糖控制不佳2个月余"入院, 明确诊断为T2DM。经评估患者合并冠心病、肥胖、血脂异常等心血管高危因素, 在既往降糖方案门冬胰岛素30注射液(早、晚各32 U皮下注射), 联合阿卡波糖胶囊(100 mg, 3次/d)、盐酸二甲双胍(0.5 g, 2次/d)基础上进行调整, 保留二甲双胍治疗同时, 联用司美格鲁肽注射液(0.5 mg, 1次/周皮下注射)控制血糖, 简化降糖方式后血糖控制良好, 患者满意。胰高糖素样肽-1受体激动剂司美格鲁肽葡萄糖浓度依赖降糖, 能有效降低血糖, 低血糖风险低, 安全性高, 同时在心血管获益、减轻体重方面具有良好作用。     

钠-葡萄糖共转运蛋白2抑制剂联合胰高糖素样肽-1受体激动剂治疗2型糖尿病的研究进展

糖尿病是全球重要的公共卫生问题, 其并发症的发生发展更加影响患者的生活质量。因此糖尿病的治疗重点不仅在于血糖的控制, 还在于降低糖尿病并发症的发生率和死亡率。近年来对降糖药物的探索中, 钠-葡萄糖共转运蛋白2抑制剂联合胰高糖素样肽-1受体激动剂治疗2型糖尿病表现出降糖、降压、减重、调脂, 改善心血管、肾脏、肝脏功能等多方面的获益。该文总结了钠-葡萄糖共转运蛋白2抑制剂联合胰高糖素样肽-1受体激动剂治疗2型糖尿病的疗效及安全性。     

艾塞那肽临床研究新进展

肠促胰素是肠道在进餐后分泌的激素,能促进胰岛素的分泌.胰高糖素样肽1(GLP-1)是主要的肠促胰素,通过葡萄糖依赖的方式促进胰岛素分泌、抑制胰高糖素分泌以及延缓胃排空、增加饱腹感等作用维持体内血糖的稳定.另外,在2型糖尿病患者中,它还可改善β细胞功能.但是天然的GLP-1半寿期很短,无法用于临床治疗.艾塞那肽是从希拉巨蜥唾液中分离得到的一种多肽,它可与GLP-1受体结合,产生与GLP-1相似的生理效应,但它的半寿期远比GLP-1长,因此每天两次皮下注射即可产生满意的疗效.临床研究显示艾塞那肽可显著降低2型糖尿病患者HbA_(1C)、空腹血糖及餐后血糖,并降低体重.动物研究表明艾塞那肽还可改善β细胞功能、增加β细胞量.由于GLP-1受体激动剂的独特疗效,新近的糖尿病治疗指南已将其列入2型糖尿病的治疗药物.     

从糖尿病的心血管疾病风险看GLP-1类似物

2型糖尿病与心血管疾病风险密切相关.对于具有多重心血管危险因素的糖尿病患者,在安全有效控制血糖的同时,应强调全面强化干预血脂、血压等并存风险因素,才能有效降低糖尿病大血管病变的发生,带来良好的心血管益处.美国食品药品监督管理局(FDA)也强调需要考虑降糖药物的心血管方面的安全性.胰升糖素样肽1(GLP-1)具有葡萄糖浓度依赖性降糖作用及β细胞保护功能,此外还可减轻体重,并具有独特的的心血管保护效应.利拉鲁肽(Liraglutide)与人GLP-1的高度同源性充分保留了GLP-1的多项生理活性,同时作用于2型糖尿病的多个病理生理靶点,发挥GLP-1的多效作用.LEAD(Liraglutide Effect and Action in Diabetes)等研究结果证实,无论其单独应用还是与其他口服降糖药联用利拉鲁肽显示了优异的降糖效果,且出现低血糖风险很低.利拉鲁肽可通过降低血压,减轻体重全面干预多种心血管疾病危险因素,显示了GLP-1在心血管风险因素防控方面独特的优势.     

胰高糖素样肽-1受体激动剂在2型糖尿病患者早期血糖达标应用中的研究进展

糖尿病的发病率和患病率逐年升高, 是全球公共卫生的主要威胁。早期强化降糖能够延缓疾病进展, 降低糖尿病并发症的发生风险。"代谢记忆"假说为早期强化代谢控制所带来的持久益处提供了解释。胰高糖素样肽-1受体激动剂(GLP-1RA)被证实在2型糖尿病人群中可以有效改善血糖, 降低体重, 相关心血管结局研究也证实大多数GLP-1RA能够显著降低心血管不良事件风险。该文汇总归纳糖尿病早期干预治疗与GLP-1RA在早期降糖以及心肾获益方面的最新临床研究进展, 解析GLP-1RA降糖及改善心血管终点的机制, 为临床提供参考。     

利拉鲁肽(Liraglutide)——糖尿病治疗领域的热点新药——来自"对话糖尿病"(Diabetes Dialogue)的会议报道

"对话糖尿病"是一个世界性的糖尿病学术论坛.2008年第五届论坛的主要议题是2型糖尿病治疗新靶点,并特别介绍了当今糖尿病治疗领域的热点--肠促胰岛激素,尤其是胰高血糖素样肽1(GLP-1)与β细胞功能的研究进展.研究结果提示在胰岛素抵抗的背景下,β细胞功能持续减退是2型糖尿病进展的典型特征.由于GLP-1具有葡萄糖依赖性降糖作用且可改善β细胞功能,目前已成为学者们探索糖尿病治疗途径的新靶点.由诺和诺德公司研发的GLP-1类似物--利拉鲁肽(Liraglutide)正是针对上述糖尿病治疗新靶点的药物之一.大量研究证实利拉鲁肽不仅具有高效、持久的降糖效果,且可以显著改善β细胞功能.这些研究结果增强了人们使用GLP-1或GLP-1类似物治疗糖尿病的信心,使利拉鲁肽成为具有广阔前景的抗糖尿病药物.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.