摘要:

Hyperglycemia is the major causal factor in the development of endothelial dysfunction in patients with diabetes mellitus. Although the mechanisms underlying this phenomenon are likely to be multifactorial, recentin vivoandin vitrostudies have indicated a crucial role of the diacylglycerol (DAG)-protein kinase C (PKC) pathway in mediating this phenomenon. PKC may have multiple adverse effects on vascular function, including the activation of superoxide-producing enzymes such as the nicotinamide adenine dinicleotide phosphate (NADPH) oxidase as well as increased expression of a dysfunctional, superoxide-producing, uncoupled endothelial nitric oxide synthase (NOS III).PKC-mediated superoxide production may inactivate nitric oxide (NO) derived from endothelial NOS III, but also may inhibit the activity and/or expression of the NO downstream target, the soluble guanylyl cyclase. Among the different isoforms of PKC, mainly the β-isoforms have been shown to be activated.Recent studies with selective (isoform-specific) and non-selective PKC inhibitors show that they are able to beneficially influence glucose-induced endothelial dysfunction in experimental animal models as well as in patients, pointing to the therapeutic potential of these compounds in the prevention and treatment of vascular complications of diabetes.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Ovarian stimulation is an integral part of assisted reproductive technologies (ART). Under physiologic conditions, both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity is necessary to guarantee follicle growth and maturation. This can be shown in patients with hypogonadotrophic hypogonadism, who have no endogenous FSH or LH activity. The use of FSH alone in these patients does not result in sufficient follicle growth and oocyte quality. Approximately 75IU of LH activity per day is necessary to guarantee optimal success. The use of gonadotropin-releasing hormone (GnRH) agonists in normogonadotrophic patients may result in suppression of LH levels below a certain threshold, resulting in suboptimal outcomes. The question under discussion in this article is the threshold level of LH below which exogenous LH activity should be added to provide optimal ovarian response. Different studies indicate that the endogenous LH level should be 0.5–1.5IU in long-term protocol situations.Patients treated in ultra-long GnRH agonist protocols, as well as older patients, patients with a low response to gonadotropin treatment, and patients treated with a GnRH antagonist protocol may benefit from exogenous LH activity. There are three ways of adding LH activity in ovarian stimulation cycles. Nowadays, lutropin alfa (recombinant LH) may be the optimal choice since it has no chorionic gonadotropin activity and allows individual dosage titration. Every menotropin preparation currently on the market contains some chorionic gonadotropin activity. However, more data are necessary before evidence-based recommendations regarding LH supplementation in ovarian stimulation protocols can be given.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Type 2 diabetes mellitus is a serious, growing, and costly public health problem. The disease is chronic and degenerative, and thus primary prevention is desirable. Observational studies have linked type 2 diabetes to specific lifestyle behaviors. Several recent major clinical trials confirm that type 2 diabetes can be delayed or prevented in people at high risk; multicomponent lifestyle modification can reduce the incidence of diabetes up to 58%. The American Diabetes Association has recently recommended that lifestyle interventions to prevent or delay diabetes be delivered to people with prediabetes. Delivery of lifestyle interventions in practice is fraught with challenges, but there are several tools and practical strategies available for the implementation of trial findings.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Contraception is an important issue for women with diabetes mellitus as unplanned pregnancy can present major maternal and perinatal complications. The rising incidence of diabetes worldwide means increasing thought needs to be given to contraceptive options for these women. This article reviews current evidence and recommends best practice for prescribing hormonal contraceptives in women with diabetes.Women with diabetes have the same choice of contraceptives as the general population, but the potential metabolic effects of hormonal methods need to be considered in relation to an individual’s diabetic profile and their need for effective contraception. Currently, there appear to be wide variations in the way that professionals evaluate the risk-benefit equation, and significant differences in prescribing practice have been identified. The World Health Organization (WHO) has established medical eligibility criteria to assist in assessing such risks.Cardiovascular disease is a major concern, and for women with diabetes who have macrovascular or microvascular complications, nonhormonal methods are recommended. Studies of young women with diabetes and no vascular changes who are taking low-dose combined oral contraceptives (COCs) have been reassuring, although larger long-term studies are needed. There is little evidence that any changes in glycemic control caused by COCs are of clinical relevance. While low-dose COCs appear to cause minimal change in the lipid profile and may even be beneficial in this respect, there are some concerns in relation to progestogen only pills and injectable contraceptives in certain women.There is little evidence of best practice for the follow-up of women with diabetes prescribed hormonal contraception. It is generally agreed that blood pressure, weight, and body mass index measurements should be ascertained, and blood glucose levels and baseline lipid profiles assessed as relevant. Research on hormonal contraception has been carried out in healthy populations; more studies are needed in women with diabetes and women who have increased risks of cardiovascular disease.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of the skeleton leading to enhanced bone fragility and an increased risk of fracture. Prior to fracture, diagnosis is established by documenting low bone mass. In the first section of this article we review the clinical use of bone mass measurements and biochemical markers of bone remodeling in selecting patients most in need of preventive therapy at menopause. Women with high bone turnover lose bone at menopause more rapidly than those with normal bone turnover and are more likely to derive benefit from the several preventive therapies available. The second section addresses the available technologies used to diagnose osteoporosis and/or establish fragility fracture risk using noninvasive bone mass measurement and biochemical markers of bone remodeling separately or in combination. In the third section we review the several treatment options available for patients with osteoporosis, including alendronate (alendronic acid), risendronate (risedronic acid), calcitonin, teriparatide, and raloxifene, and the approaches to monitoring the therapeutic response. The final section deals with fall protection – an often forgotten aspect of management of the patient at risk for sustaining and osteoporotic fragility fracture.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Experimental and clinical studies indicate that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are involved in heart development. Impaired cardiovascular function, as recently demonstrated, could potentially reduce life expectancy both in GH deficiency (GHD) and excess. Patients with childhood- or adult-onset GHD may have both cardiac structural and functional abnormalities, i.e. reduced cardiac mass, reduced diastolic filling, and impaired left ventricular response to peak exercise. In addition, GHD patients may present with an increase in vascular intima-media thickness and a higher occurrence of atheromatous plaques that can further aggravate the hemodynamic conditions and contribute to the increased cardiovascular and cerebrovascular risk. However, some evidence has been provided to show that cardiovascular abnormalities can be partially reversed after somatropin (recombinant GH) therapy in patients with GHD.Recently, somatropin administration was shown to induce improvement in hemodynamics and clinical status in some patients with heart failure. Although these data need to be confirmed in more extensive studies, such promising results open new perspectives for somatropin therapy. The role of GH secretagogues in heart failure is still unknown.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

More than three decades since the original published description of gestational diabetes mellitus (GDM), no consensus exists regarding its implications or management. Targeting fetal macrosomia as the greatest morbidity, treatment strategies for this pregnancy-induced disease of insulin resistance have largely been modeled from therapies proven successful in pregnant women with type 2 diabetes mellitus. Surrounded by a rapidly expanding array of treatment options for insulin-resistant diabetes, potentially legitimate concerns about teratogenicity and fetal metabolic effects have limited clinical trials of insulin analogs and oral antihyperglycemic agents during pregnancy. So far, only insulin lispro and glyburide (glibenclamide) have been tested prospectively in randomized trials of women with GDM. In limited studies, both of these agents have compared favorably with standard insulin regimens, and neither appear to cause any fetal or neonatal harm. Although acknowledged by the American Diabetes Association (ADA) and the American College of Obstetricians and Gynecologists (ACOG), these seminal studies have not yet prompted a recommendation from either organization on how to utilize insulin analogs or oral antihyperglycemic agents in the treatment of GDM. Although they lack an evidence base for many therapeutic strategies for GDM, the current ADA and ACOG guidelines still provide a reasonable set of treatment recommendations.

ISSN:1175-6349    

出版商:ADIS    

年代:2003

数据来源: ADIS