二甲双胍50年进程

二甲双胍可通过减少肝脏葡萄糖输出,提高胰岛素的敏感性,改善胰岛素抵抗等作用降低血糖.目前,美国糖尿病联合会和欧洲糖尿病研究学会达成共识,认为二甲双胍是治疗2型糖尿病的一线用药并贯穿治疗始终.除降低血糖外,二甲双胍在改善脂代谢,保护血管,以及治疗非酒精性脂肪肝和多囊卵巢综合征等疾病的运用中都发挥着独特的作用.最新的研究发现,二甲双胍对促甲状腺激素也有一定影响.二甲双胍最常见的不良反应为胃肠道反应.乳酸酸中毒则非常罕见,故能安全地用于糖尿病前期与糖尿病的治疗.许多大型临床研究如英国前瞻性糖尿病研究均已证实二甲双胍治疗可对心血管疾病的预后产生有益影响.     

二甲双胍的临床应用进展

口服降血糖药二甲双胍用于治疗2型糖尿病已有49年的历史,近年发现二甲双胍有增加胰岛素敏感性等多方面的药理作用,从而拓宽了以胰岛素抵抗为中心的疾病如肥胖症、糖耐量减低、非酒精性脂肪肝、代谢综合征、多囊卵巢综合征、肝纤维化等症防治的适应证。本文介绍二甲双胍的临床应用进展。     

观察使用格列齐特缓释片、二甲双胍、阿卡波糖联合治疗对2型糖尿病的降糖作用和对胰岛素的影响

目的观察使用格列齐特缓释片、二甲双胍、阿卡波糖联合治疗对2型糖尿病的降糖作用和对胰岛素的影响。方法选择该院于2018年4月—2019年4月期间收治的120例2型糖尿病患者为该次研究对象,将所有患者按照治疗方案的不同分为对照组(n=60)与研究组(n=60),对照组采用二甲双胍治疗方案,研究组应用格列齐特缓释片、二甲双胍、阿卡波糖联合治疗方案,对比分析两组患者血糖水平、空腹胰岛素和胰岛素抵抗指数。结果观察组患者空腹血糖、餐后2 h血糖明显低于对照组,研究组空腹胰岛素高于对照组,同时胰岛素抵抗指数低于对照组(P<0.05)。结论针对2型糖尿病患者采用格列齐特缓释片、二甲双胍、阿卡波糖联合治疗效果尤为显著,能够有效降低患者血糖水平,提高体内胰岛素水平,同时降低胰岛素抵抗作用,临床使用价值较高。     

二甲双胍治疗糖尿病血管并发症的防治研究

目的研究二甲双胍对糖尿病血管并发症的临床疗效。方法选取自该院2013—2014年收治的80例2型糖尿病患者作为研究对象,采用口服二甲双胍250~500 mg,每天3次进行治疗。治疗3个月后,观察前后胰岛素抵抗指数、内皮依赖性血管舒张功能与非内皮依赖性血管舒张功能、血清TNF-α和可溶性细胞内粘附分子等数据变化。结果治疗后NMD明显改善,HOMA-IR出现降低趋势,空腹血糖、血胰岛素、血清以及s ICAM-I水平均下降,差异有统计学意义(P0.05)。结论二甲双胍针对糖尿病血管并发症,不仅可以阻止动脉粥样硬化的发生发展、降低心血管发生概率,而且能够减轻心肌缺血-再灌注损伤、抑制心肌重构、延缓心力衰竭的进展。     

盐酸二甲双胍治疗老年2型糖尿病合并非酒精性脂肪肝的疗效

<正>目前我国非酒精性脂肪肝(NAFLD)的临床发病率越来越高,尤其在老年人群中与其他慢性疾病(如2型糖尿病)伴发的NAFLD特别常见〔1〕。目前,NAFLD的病因及发病机制尚未得到完全阐明。越来越多的临床研究显示〔2〕,NAFLD与代谢紊乱综合征(如脂肪代谢紊乱、胰岛素抵抗、氧化应激等)关系密切。二甲双胍可多种机制增强胰岛素敏感性,缓解胰岛素抵抗,调节血糖水平。有研究显示〔3〕,二甲双胍还可使NAFLD患者肝脏的脂肪含量减少,进而避免肝细胞受损。本研究通过拟观察二甲双胍治疗前后NAFLD患者相关血生化指标的变化。     

二甲双胍在70例2型糖尿病患者治疗临床分析

目的探讨应用二甲双胍对糖尿病患者进行治疗的临床价值。方法选择2012年2月—2013年5月在该院接受治疗的70例2型糖尿病患者给予二甲双胍进行治疗,并对患者接受治疗后3个月的空腹血糖、空腹胰岛素、餐后2 h血糖及胰岛素等各项指标进行观察比较。结果接受二甲双胍治疗后,患者的胰岛素、血糖、糖化血红蛋白水平、LDL-C、TG等均有明显下降,与治疗前相比差异有统计学意义(P<0.05)。结论应用二甲双胍治疗糖尿病可有效提高临床治疗效果,值得临床推广应用。     

探讨胰岛素或磺脲类药物联合二甲双胍治疗初发2型糖尿病的临床疗效

目的分析胰岛素或磺脲类药物联合二甲双胍治疗在初发2型糖尿病患者治疗中的临床效果。方法选取2014年1月—2015年1月期间,该院收治的初发2型糖尿病患者92例,随机分为观察组与对照组,各46例,对照组采用磺脲类药物联合二甲双胍进行治疗,观察则采用胰岛素联合二甲双胍进行治疗,观察两组患治疗后的血糖情况,胰岛素指标以及并发症发生情况。结果治疗后,观察组患者的血糖水平与胰岛素指标等显著优于对照组(P0.05),并发症发生率疗效显著低对照组(P0.05)。结论胰岛素或磺脲类药物联合二甲双胍治疗在初发2型糖尿病患者治疗中均有显著的临床效果,但胰岛素联合应用二甲双胍治疗的临床效果更为显著,值得在临床上推广和应用。     

二甲双胍对2型糖尿病患者血管内皮功能的影响

目的研究二甲双胍对2型糖尿病患者血管内皮功能的影响。方法 93例血糖控制不满意的2型糖尿病(T2DM)患者随机分为二甲双胍组(500 mg,3次/d)及吡格列酮组(15 mg,1次/d),疗程12个月。观察血管内皮功能的变化。结果与治疗前相比,治疗12个月后两组患者的血糖、胰岛素抵抗指数(IRI)均显著下降,空腹及餐后胰岛素水平、胰岛素功能均显著升高(均P0.05)。治疗12个月后两组患者血糖、IRI、胰岛素水平、胰岛素功能比较,差异均无统计学意义(均P0.05);但治疗12个月后二甲双胍组的体质指数(BMI)低于吡格列酮组(P0.05)。与治疗前相比,治疗12个月后两组患者的血管内皮功能均显著改善(均P0.05),但治疗12个月后二甲双胍组的血管内皮功能改善优于吡格列酮组(P0.05)。结论二甲双胍与吡格列酮两种药物对T2DM患者均具有明显的降糖、改善胰岛素功能、降低胰岛素抵抗(IR)及改善血管内皮功能的作用。在降低BMI及改善血管内皮功能方面,二甲双胍优于吡格列酮。     

抗阻力运动联合二甲双胍治疗2型糖尿病的临床效果研究

选择2018年4月-2019年4月86例2型糖尿病患者,随机平分为对照组予以二甲双胍口服,研究组联合应用抗阻力运动。结果干预后,研究组血糖水平、胰岛素抵抗指数改善程度高于对照组,(P 0. 05),结论抗阻力运动联合二甲双胍,有助于控制2型糖尿病血糖水平变化,改善胰岛素抵抗指数。     

沙格列汀联合二甲双胍对老年糖尿病患者血糖及胰岛素敏感性的影响

目的探讨沙格列汀联合二甲双胍对老年糖尿病患者血糖及胰岛素敏感性的影响。方法回顾性分析自2016年1月—2017年6月期间门诊收治的97例老年糖尿病患者临床资料。对照组口服二甲双胍控制血糖,观察组口服沙格列汀联合二甲双胍控制血糖。对比两组患者治疗前后的空腹血糖、餐后2 h血糖、糖化血红蛋白、空腹胰岛素、BMI以及胰岛素抵抗指数(HOMA-IR)。结果两组患者治疗后的空腹血糖、餐后2 h血糖以及糖化血红蛋白均显著低于治疗前(P0.05);观察组治疗后的空腹血糖,餐后2 h血糖,糖化血红蛋白均显著低于对照组(P0.05);两组患者治疗后的空腹胰岛素水平均显著高于治疗前,而HOMA-IR均显著低于治疗前(P0.05);观察组治疗后的空腹胰岛素显著高于对照组,而HOMA-IR显著低于对照组(P0.05)。结论沙格列汀联合二甲双胍可有效控制老年2型糖尿病患者的血糖水平,改善其胰岛素抵抗和胰岛素分泌功能。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

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.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.     

Language of CTO interventions – Focus on hardware

The knowledge of variety of chronic total occlusion (CTO) hardware and the ability to use them represents the key to success of any CTO interventions. However, the multiplicity of CTO hardware and their physical character and the terminology used by experts create confusion in the mind of an average interventional cardiologist, particularly a beginner in this field. This knowledge is available but is scattered. We aim to classify and compare the currently used devices based on their properties focusing on how physical character of each device can be utilized in a specific situation, thus clarifying and simplifying the technical discourse.