2型糖尿病血脂异常及治疗

2型糖尿病血脂异常的特点为低密度脂蛋白胆固醇轻中度升高,高三酰甘油血症和高密度脂蛋白胆固醇降低,以及小而密低密度脂蛋白颗粒升高,且脂蛋白颗粒本身功能常常受损。对糖尿病患者动脉粥样硬化性心血管疾病的发生和发展起着重要促进作用,并导致残余风险增加。近年来大量临床研究肯定了他汀类药物在糖尿病患者动脉粥样硬化心血管疾病防治的基石地位。而传统的非他汀类的调脂药物,如烟酸和贝特类的证据不充分。新型非他汀调脂药物如胆固醇吸收抑制剂和前蛋白转化酶枯草杆菌蛋白酶9抑制剂在糖尿病患者均显示良好的疗效,是降低残余心血管病风险的有效手段;但需要关注调脂药物对糖代谢的不利影响。     

新观点

权衡他汀类药物的利与弊 他汀类药物可以降低LDL（“坏”胆固醇）水平,这一点对心血管疾病的防治十分有益。但是他汀类药又会升高2型糖尿病的发病风险,这让一些医生和患者感到很棘手。最近有学者对20个国家的56项研究进行了分析,得出结论是他汀类药可使心血管疾病风险降低19％～38％;使2型糖尿病风险升高8％～25％。     

糖尿病血脂异常的处理进展

糖尿病血脂异常主要表现为三酰甘油和小而致密低密度脂蛋白颗粒增高、高密度脂蛋白胆固醇降低、脂蛋白功能或质量异常,其发生机制主要与胰岛素抵抗和脂蛋白糖化有关。在处理糖尿病血脂异常时,应注重糖尿病心血管并发症的综合防治。改善生活方式和使用他汀类药物、胆固醇吸收抑制剂或PCSK9抑制剂以降低低密度脂蛋白胆固醇,仍是糖尿病血脂异常管理的主流。对三酰甘油明显增高的糖尿病患者,也可在注意不良反应的情况下,考虑联合应用贝特类药物或特殊疗法。新型降糖药物有助于调脂和降低心血管死亡率。     

甘油三酯增高的血脂异常防治中国专家共识

血脂异常是心血管系统最重要的危险因素之一。大量临床研究证实,应用他汀类药物降低胆固醇水平可以降低动脉粥样硬化性心血管疾病的发生率与致死致残率。然而近年研究显示,血脂异常患者即使经过大剂量他汀强化降胆固醇治疗后仍面临很高的心血管剩留风险Ⅲ,而在2型     

关注高甘油三酯血症防治

<正>血脂异常是心血管系统最重要的危险因素之一。大量临床研究证实,应用他汀类药物降低TC水平,可以减低动脉粥样硬化性心血管病的发生率、致死率、致残率。然而,近年研究显示,血脂异常患者即使经过大剂量他汀类药物强化降TC治疗后,仍面临很高的心血管剩留风险,而TG升高和HDL-C降低是构成心血管剩留风险的主要血脂异     

减少心血管剩留风险的调脂药物

尽管接受了标准治疗,冠心病和(或)2型糖尿病患者仍可能存在心血管剩留风险.目前认为,致动脉粥样硬化性血脂异常是导致心血管剩留风险的重要因素.以他汀类药物为主的调脂治疗并不能完全解决高甘油三酯(triglyeride,TG)和低高密度脂蛋白胆固醇(high density lipoproteincholesferol,HDK-C)所致的血管风险.因此,以高TG和低HDL-C为靶标的治疗已引起医生的重视,改变生活方式及他汀类药物联合贝特类药物或烟酸以全面改善血脂异常的治疗措施备受关注.     

减少心血管剩留风险的调脂药物

尽管接受了标准治疗,冠心病和(或)2型糖尿病患者仍可能存在心血管剩留风险.目前认为,致动脉粥样硬化性血脂异常是导致心血管剩留风险的重要因素.以他汀类药物为主的调脂治疗并不能完全解决高甘油三酯(triglyeride,TG)和低高密度脂蛋白胆固醇(high density lipoproteincholesferol,HDK-C)所致的血管风险.因此,以高TG和低HDL-C为靶标的治疗已引起医生的重视,改变生活方式及他汀类药物联合贝特类药物或烟酸以全面改善血脂异常的治疗措施备受关注.     

减少心血管剩留风险的调脂药物

尽管接受了标准治疗,冠心病和(或)2型糖尿病患者仍可能存在心血管剩留风险.目前认为,致动脉粥样硬化性血脂异常是导致心血管剩留风险的重要因素.以他汀类药物为主的调脂治疗并不能完全解决高甘油三酯(triglyeride,TG)和低高密度脂蛋白胆固醇(high density lipoproteincholesferol,HDK-C)所致的血管风险.因此,以高TG和低HDL-C为靶标的治疗已引起医生的重视,改变生活方式及他汀类药物联合贝特类药物或烟酸以全面改善血脂异常的治疗措施备受关注.     

选择性胆固醇吸收抑制剂临床应用中国专家共识(2013版)

血脂异常与心血管疾病密切相关.过去10余年中,国内外先后完成了一系列里程碑式的血脂干预临床试验.这些研究结果有力证实,降低胆固醇水平显著降低心血管病患者其高危人群的心血管事件发生率,因而降胆固醇达标被视为防治心血管疾病的核心策略.确凿证据表明,他汀类药物在动脉粥样硬化性心血管疾病一、二级预防中具有重要地位,合理应用此类药物显著降低心血管疾病的发病率与病死率.临床实践中,许多患者接受他汀类药物治疗后其胆固醇水平仍不能达到目标值,另有一些患者不能耐受他汀类药物治疗,已成为提高血脂达标率的重要羁绊.此外,为使胆固醇达标,应用大剂量他汀类药物的安全性也正引起越来越多的关注.他汀类药物剂量加倍后其降胆固醇作用仅增加6％左右,但相关不良事件(特别是肝酶升高、肌病以及对糖代谢的影响)的风险与他汀类药物剂量相关,不良事件发生风险显著增加.     

新版《中国成人血脂异常防治指南》6大精髓抢先看

正2016年10月24日,《中国成人血脂异常防治指南(2016年)》发布,其主要更新要点如下:1血脂异常患病率升高我国成年人血脂异常患病率为40.40%,较2002年大幅度升高。其中,高胆固醇血症患病率为4.9%,高三酰甘油血症患病率为13.1%,高低密度胆固醇血症患病率为33.9%。2他汀类药物有效减少心脑血管事件的作用得到首肯近20年来多项大规模临床试验结果显示,他汀类药物在一、二级预防中均能有效降低心血管事件发生风险,已成为防治心脑血管事件的重要药物。为了调脂达标,临床上应首选他汀类药物(Ⅰ类推荐,A级证据)。他汀类药物     

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.     

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.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.