衰老相关的慢性炎症与胰岛素抵抗的研究进展

慢性炎症是衰老和衰老相关疾病的一个主要发病风险因素,而胰岛素抵抗也在衰老过程中发挥作用。慢性炎症通过损害正常的脂质分布、脂肪组织功能、线粒体功能以及内质网应激引起胰岛素抵抗。脂肪组织的异常分布又可引起慢性炎症,慢性炎症进一步加剧胰岛素抵抗,慢性炎症和胰岛素抵抗相互作用可加速衰老过程。然而,一些研究表明,胰岛素抵抗本身也增加慢性炎症的作用。其中胰岛素依赖Akt信号传导通路的活性特别重要,因为它在胰岛素敏感器官如肝脏和肌肉中分布减少,并在非代谢器官如肾和主动脉中分布增加,原因可能是胰岛素抵抗和高胰岛素血症。     

胰岛素抵抗与肾脏病的关系

代谢综合征已成为当今社会的一个公共卫生问题。胰岛素抵抗是代谢综合征发病的中心环节,可以通过多种途径导致肾损害,而肾脏病也可以进一步干扰糖代谢,加重胰岛素抵抗,从而形成恶性循环。明确两者关系,在肾脏病防治过程中显得越来越重要。     

慢性肾脏病患者胰岛素抵抗的研究进展

慢性肾脏病（CKD）已逐渐成为世界范围的重要公共卫生问题之一.CKD患者常伴有糖代谢异常,临床可表现为空腹血糖受损（IFG）、糖耐量减低（IGT）、显性糖尿病（DM）等,其中IFG及IGT被认为是糖尿病发展前期.CKD患者随着肾脏功能下降,胰岛素代谢清除能力下降、尿毒症毒素蓄积、维生素D缺乏、继发性甲状旁腺功能进（SPTH）、肾性贫血,亦可伴有氧化应激及炎症等因素使胰岛素分泌减少及胰岛素抵抗（IR）增加,加重CKD患者糖代谢异常的发生和发展.     

胰岛素抵抗与高血压的关系

研究表明胰岛素抵抗与高血压密切相关,胰岛素抵抗是高血压的一个独立危险因子,二者存在理论上的因果关系.胰岛素抵抗在高血压的发病机制中起至关重要的作用,而高血压也可影响胰岛素的代谢,造成胰岛素抵抗,两者相辅相成,导致一系列严重慢性并发症的发生.同时,多种降压药物可通过影响糖代谢从而改善胰岛素抵抗,另一方面,部分改善胰岛素抵抗的药物可用于治疗原发性高血压.因此,了解胰岛素抵抗与高血 压之间的关系对于胰岛素抵抗及高血压的防治有重要意义.     

肝源性胰岛素抵抗的研究进展

慢性肝病与胰岛素抵抗紧密相关,互相促进,已经成为近年来研究的热点,本文就病毒性肝炎、肝硬化、肝癌等在胰岛素抵抗方面的新进展作一综述.     

肿瘤坏死因子-α与胰岛素抵抗关系的研究进展

胰岛素抵抗,是指机体胰岛素介导的葡萄糖摄取和代谢能力减低,包括胰岛素的敏感性和反应性下降,它是肥胖和T2DM发病机制的一个共同特征.目前认为肥胖是一种慢性低度非特异性炎症反应,肥胖时脂肪细胞分泌多种细胞因子,参与胰岛素抵抗的发生,如TNF-α、抵抗素、瘦素、IL-6等.其中TNF-α在胰岛素抵抗的发生机制中占有极其重要的地位,本文就近期这方面的研究进行综述.     

胰岛素抵抗与支气管哮喘的研究进展

支气管哮喘(简称哮喘)是由多种因素引起的异质性疾病,目前公认的发病机制之一是气道慢性炎症假说,但仍未完全明确.近来研究表明,胰岛素抵抗与哮喘发病机制密切相关.本文综述胰岛素及胰岛素受体、胰岛素信号通路、胰岛素抵抗相关细胞因子在哮喘发病中的作用机制,将有望在哮喘的治疗方面提出新的治疗方向和靶点.     

代谢综合征与微炎性反应

代谢综合征(MS)是指以糖尿病、肥胖、血脂异常、高血压等为表现的临床症候群,由世界卫生组织在1998年正式命名.随着对MS研究的不断深入,现在普遍认为MS患者体内存在微炎性反应(microinflammation),并且这种微炎性反应还在进一步加重MS,并促进一些临床并发症的出现,具体表现在胰岛素抵抗的加重、高血压的恶化、动脉粥样硬化或心血管疾病的出现以及慢性肾脏病的进展等.本文就近年来关于MS和微炎性反应关系的研究作一综述.     

代谢综合征和肾脏损害

代谢综合征(metabolicsyndrome,MS),早期又被称作胰岛素抵抗综合征,是以胰岛素抵抗为中心环节,肥胖为启动因素所引起的代谢紊乱征候群。其组成部分包括中心性肥胖(又称腹部肥胖或内脏性肥胖)、胰岛素抵抗、高血压、高脂血症、高血凝和微炎症状态等[1-3]。代谢综合征相关性疾病,特别是MS和慢性肾脏病的关系,越来越受到人们的关注,在此我们做一综述。1代谢综合征的诊断代谢综合征的临床诊断标准主要有以下5种:(1)美国胆固醇教育计划成人治疗指南Ⅲ(ATPⅢ)标准。(2)美国临床内分泌医师学会(AACE)标准。(3)世界卫生组织(WHO)标准。(4)国际…     

早相胰岛素分泌的病理生理及临床意义

目前我国约有4000万糖尿病患者,其中90%～95%是2型糖尿病.糖尿病最严重的问题是其常见的慢性血管合并症.胰岛素抵抗、B细胞功能不全是其发病的原因,胰岛素抵抗只在B细胞分泌胰岛素的功能不能足够代偿时才引起发病.     

Insulin resistance and endothelin: another pathway for renal injury in patients with the cardiometabolic syndrome?

Recent population studies suggest that insulin resistance and hyperinsulinemia, as well as the presence of the cardiometabolic syndrome, are associated with increased risk of chronic kidney disease. A considerable number of background studies support this association, proposing several mechanisms through which insulin resistance and hyperinsulinemia can harm the normal kidney. Current knowledge suggests that activation of the endothelin system can be an important factor contributing to the development of renal injury. Moreover, data from in vitro and in vivo studies have clearly shown that hyperinsulinemia stimulates the production and action of endothelin-1, an effect that is sustained in insulin-resistant states. Thus, insulin-mediated activation of the endothelin system can be another important pathway linking insulin resistance with kidney injury. This article discusses the existing data on the interactions between insulin resistance, hyperinsulinemia, and endothelin and how these can lead to renal damage in patients with the cardiometabolic syndrome.     

Insulin resistance and oxidant stress: an interrelation with deleterious renal consequences?

Within the past years, several epidemiologic studies have shown that insulin resistance and hyperinsulinemia are associated with chronic kidney disease, and experimental data suggest that a number of background mechanisms could connect insulin resistance with renal injury. Moreover, the acute sodium-retaining action of insulin at the kidney level has been proposed to participate in the development of salt sensitivity in essential hypertension. Current knowledge suggests that oxidative stress can be involved in the development of renal injury and can also promote primary salt retention at the kidney level. Insulin resistance and hyperinsulinemia seem to be closely connected with oxidative stress in the form of a vicious circle. This article discusses the potential role of oxidative stress as a mediator of the renal effects of insulin resistance/hyperinsulinemia.     

Disturbances in renal autoregulation and the susceptibility to hypertension-induced chronic kidney disease

The risk of developing chronic kidney disease in the setting of hypertension varies among patient populations. Black hypertensive patients have an increased risk of developing hypertension-induced chronic kidney disease even after taking into account socioeconomic factors. There is evidence to suggest that the kidney is intrinsically more susceptible to the damaging effects of hypertension in black patients. This susceptibility can be traced to disturbances in the way the kidney autoregulates. Impaired renal autoregulation may be the renal manifestation of a more widespread abnormality in endothelial function. Other conditions that can impair renal autoregulation and add to the risk of chronic kidney disease include low birth weight, obesity, insulin resistance, hyperuricemia, and hypercholesterolemia. To minimize the risk of chronic kidney disease in patients with impaired renal autoregulatory capability, strict blood pressure control is required. There is indirect evidence that blocking the renin-angiotensin system may improve renal autoregulation.     

代谢综合征与肾脏疾病值得探讨的几个问题

代谢综合征是以肥胖相关胰岛素抵抗为基础的一组疾病,其中每一项异常都是心血管疾病和肾脏疾病的危险因素,同时它本身表现为一种低度系统性慢性炎症状态,进一步促进肾脏损害的发生及发展.现就代谢综合征的各项组成部分与慢性炎症状态及肾脏损害之间的关系作一综述.     

Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease

The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate 30 m L/min per 1.73 m~2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.     

Metabolic syndrome and chronic kidney disease

The prevalence of metabolic syndrome (MetS) is increasing worldwide in both developing and developed countries. Experimental and clinical studies have revealed that MetS plays an important role in the development of chronic kidney disease (CKD), which leads to end-stage renal disease. Emerging evidence also suggests that CKD may actually cause MetS since the kidney is an important organ of glucose and lipid homeostasis. Although multiple mechanisms have been shown to be involved in the pathogenesis of MetS, insulin resistance appears to be a central pathophysiological factor contributing to MetS. In this review we will discuss the association of MetS with insulin resistance and CKD, and the renal pathophysiological changes associated with MetS.     

Thiazolidinediones and diabetic nephropathy: need for a closer examination?

Diabetic nephropathy is an important public health issue and a major challenge for modern nephrology, as it is the primary cause of end-stage renal disease. In addition to established risk factors for diabetic nephropathy progression (ie, hyperglycemia and hypertension), current knowledge suggests that other factors can be involved. Population studies show that insulin resistance and hyperinsulinemia are also associated with chronic kidney disease, and several background mechanisms could explain this relationship. The hypoglycemic class of thiazolidinediones that act through reduction of insulin resistance were found to protect against renal injury in diabetic animals and to reduce urinary albumin excretion in patients with type 2 diabetes and microalbuminuria. This renoprotective action is supported by relevant studies showing that thiazolidinediones act beneficially on most of the players involved in diabetic nephropathy progression. Recent studies have raised uncertainty about the cardiovascular safety of thiazolidinediones. After the latter issue is resolved, however, it would appear very interesting to conduct specific studies in patients with overt diabetic nephropathy to determine the effect of these agents on proteinuria and kidney disease progression.     

Insulin resistance and lower plasma adiponectin increase malignancy risk in nondiabetic continuous ambulatory peritoneal dialysis patients

End-stage renal disease patients have a higher risk for developing cancer. Although several causes for this increased risk have been proposed, the risk factors for cancer development in this population have not been elucidated. The aim of this study was to determine whether metabolic derangements, including insulin resistance and altered adipokines, increase the risk of developing malignancies in peritoneal dialysis (PD) patients, who are vulnerable to metabolic disorders because of excessive glucose absorbed from the dialysate. Study subjects comprised 106 nondiabetic PD patients who had been on PD for a minimum of 3 months with no overt malignancy. Baseline anthropometry, fasting glucose, insulin, and adiponectin were measured. The development of malignancy was evaluated during the follow-up period. During the mean follow-up of 47.0 ± 23.7 months, malignancy occurred in 15 patients (14.2%). The most common site of cancer was the kidney (26.7%), followed by thyroid (13.3%) and stomach (13.3%). Baseline insulin levels and homeostasis model assessment of insulin resistance were significantly higher, whereas plasma adiponectin levels were significantly lower, in patients who developed malignancy. Cox proportional hazards analysis revealed that insulin levels, homeostasis model assessment of insulin resistance, and lower adiponectin were independent predictors of malignancy. These findings demonstrate that insulin resistance and lower adiponectin levels could be risk factors for malignancy in nondiabetic PD patients.     

Triad of metabolic syndrome, chronic kidney disease, and coronary heart disease with a focus on microalbuminuria death by overeating

Coronary heart disease remains a major cause of morbidity and mortality in the United States, and its incidence is rising worldwide. Because atherosclerosis is a chronic process, and it is often associated with certain lifestyle and risk factors such as hypertension, dyslipidemia, and insulin resistance, much emphasis is being placed on lifestyle modification and control of risk factors. It is being recognized that some lifestyle patterns such as overeating result in metabolic syndrome, which may play a role in the development of chronic kidney disease and coronary heart disease. Here, we focus on an important relationship between these 3 conditions, and we provide evidence that microalbuminuria develops in many patients with metabolic syndrome, may be an important correlate of chronic kidney disease and coronary heart disease, and may represent an important prognostic marker. Although the pathogenesis of microalbuminuria in metabolic syndrome is not clear, we suggest that microalbuminuria, chronic kidney disease, and coronary heart disease share common pathways involving inflammation and oxidative stress. We also discuss that a healthy lifestyle is essential for preventing and treating chronic kidney disease and coronary heart disease seen in patients with metabolic syndrome.     

Challenges in management of diabetic ketoacidosis in hemodialysis patients,case presentation and review of literature

Chronic kidney disease is associated with accumulation of uremic toxins that increases insulin resistance which will lead to blunted ability to suppress hepatic gluconeogenesis and reduce peripheral utilization of insulin. CKD patients fail to increase insulin secretion in response to insulin resistance because of acidosis, 1,25 vitamin D deficiency, and secondary hyperparathyroidism. Hemodialysis causes further fluctuations in glycemic control due to alterations in insulin secretion, clearance and resistance. DKA is uncommon in hemodialysis patients because of the absence of glycosuria and osmotic diuresis which accounts for most of the fluid and electrolyte losses seen in DKA, anuric patients may be somewhat protected from dehydration and shock, although still subject to hyperkalemia and metabolic acidosis. However, substantial volume loss can still occur due to a prolonged decrease in oral intake or increased insensible water losses related to tachypnoea and fever. There is no current guidelines for the management of diabetic ketoacidosis in anuric hemodialysis patients considering their differences than general population. In this review article we reviewed the literature and came with specific recommendations for management of Ketoacidosis in patients with CKD treated by hemodialysis.