Posttransplant diabetes and hypertension: Pathophysiologic insights and therapeutic rationale

New-onset diabetes after transplantation and hypertension are very common after renal transplantation and are associated with adverse graft and cardiovascular outcomes. A thorough understanding of the unique factors that operate in renal transplant recipients is essential for the proper evaluation and management of these important disorders. This review outlines the pathogenesis, diagnostic workup, and therapeutic rationale for diabetes and hypertension after transplantation.     

Pathophysiologic, diagnostic, and therapeutic aspects of the metabolic syndrome

The metabolic syndrome, characterized by increases in waist circumference, blood pressure, and triglyceride concentrations combined with reduced high-density lipoprotein and evidence of glucose intolerance, results from the interaction of visceral or central obesity with insulin resistance. This syndrome presents a clinical situation of systemic inflammation and increased cardiovascular risk. Blood pressure, even if only in the "prehypertensive" range, plays an important role in increasing the risk of cardiovascular disease. Recognition and treatment of each individual component of the metabolic syndrome is critical in reducing cardiovascular risk. Treatment should begin with lifestyle changes, including diet, exercise, and weight reduction. Antihypertensive therapy should be directed toward reduction of blood pressure to levels as close to optimal (<120/80 mm Hg) as feasible, and treatment protocols that do not cause worsening of glucose intolerance should be selected. Therapy for dyslipidemia should be directed at reducing triglycerides and increasing high-density lipoprotein. Glucose-lowering agents may be indicated, and drugs such as metformin and thiazolidinediones, which reduce insulin resistance, should form the basis of therapy. Carefully chosen therapy will effectively improve cardiovascular outcomes.     

Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions

Inflammation in the vasculature might be an important pathogenic link between cardiovascular diseases and the metabolic syndrome. Inflammation can be reduced by a variety of approaches including diet, exercise, cardiovascular drugs, and insulin sensitizers. Importantly, these different measures improve vascular function and reduce inflammation by distinct mechanisms. Therefore, combination therapy including lifestyle modifications and multiple drugs from separate classes might produce additive beneficial outcomes. We review plausible mechanisms for effects of combination therapy to reduce inflammation, improve endothelial dysfunction, and decrease insulin resistance in atherosclerosis, coronary heart disease, and hypertension in the context of insulin-resistant states including diabetes, obesity, and the metabolic syndrome.     

Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions.

Inflammation in the vasculature might be an important pathogenic link between cardiovascular diseases and the metabolic syndrome. Inflammation can be reduced by a variety of approaches including diet, exercise, cardiovascular drugs, and insulin sensitizers. Importantly, these different measures improve vascular function and reduce inflammation by distinct mechanisms. Therefore, combination therapy including lifestyle modifications and multiple drugs from separate classes might produce additive beneficial outcomes. We review plausible mechanisms for effects of combination therapy to reduce inflammation, improve endothelial dysfunction, and decrease insulin resistance in atherosclerosis, coronary heart disease, and hypertension in the context of insulin-resistant states including diabetes, obesity, and the metabolic syndrome.     

Hypertension and the metabolic syndrome

The cause of hypertension in the metabolic syndrome is complex and multifactorial and all of the elements of the metabolic syndrome, including obesity, insulin resistance, and the characteristic dyslipidemia probably are involved in mediating changes ultimately resulting in hypertension and modifying its course. Of these elements, obesity may play the most important and pivotal role in creating the conditions that lead to hypertension in the metabolic syndrome. This is not to say that the other elements of the syndrome are less important, and, as we gain more insight into the processes involved, we should be able to better manage the disease and tailor our therapeutic interventions appropriately.     

Hypertension in the metabolic syndrome

Increased blood pressure is considered an important component of metabolic syndrome. More than 85% of those with metabolic syndrome, even in the absence of diabetes, have elevated blood pressure (BP) or hypertension. The association of elevated BP with the metabolic syndrome is strongly linked through the causative pathway of obesity. Hypertension is the leading metabolic syndrome risk factor that predisposes to increased cardiovascular morbidity and mortality, and is additionally an important risk factor for development of chronic kidney disease in the presence of obesity, the metabolic syndrome, and microalbuminuria. Control of blood pressure in persons with the metabolic syndrome may prevent a significant number of coronary heart disease events. The primary modality of treatment is lifestyle intervention with reduced caloric intake and increased physical activity. Pharmacologic intervention is indicated on the basis of the severity of BP elevation, associated cardiovascular risk factors, and the presence of target organ damage.     

Hypertension and the metabolic syndrome

The metabolic syndrome is a highly prevalent condition in the United States and it has been estimated from the Third National Health and Nutrition Examination Survey that approximately 40 million individuals fulfill the diagnostic criteria, which include a waist circumference greater than 40 inches in men and 35 inches in women, triglycerides in excess of 150 mg/dL, and a high-density lipoprotein cholesterol under 40 mg/dL in men or under 50 mg/dL in women. Additionally, a blood pressure in excess of 130/85 mm Hg and a fasting plasma glucose above 110 mg/dL is required. The diagnosis of the metabolic syndrome requires at least three of the five major criteria for qualification. Hypertension, dyslipidemia, and diabetes frequently cluster and share common pathogenetic mechanisms, resulting in a complex interplay between these apparently disparate risk factors. This review centers on the common metabolic pathways that are common to the major conditions seen in the metabolic syndrome, and centers on the central role of hypertension and the clinical impact of drug therapy on other metabolic parameters.     

Hypertension in black people: pathophysiology and therapeutic aspects

Salt sensitivity is regarded as an important contributor to the higher risk of hypertension in black people as compared with whites. This finding is in agreement with a better response to diuretics than to monotherapy with angiotensin-converting enzyme (ACE) inhibitor in black subjects. It is important to remember that the hypotensive effect of ACE inhibitor is augmented in patients on a thiazide diuretic. Moreover, the antihypertensive response to a specific drug varies among black patients. Thus, ACE inhibitors should also be viewed as important options to treat hypertensive black subjects. Results from clinical trials support an emphasis on lifestyle modification and a more intensive blood pressure lowering by pharmacological interventions to reduce the large black-white gap in cardiovascular events and end-stage renal disease (ESRD) attributed to hypertension.     

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随着社会经济的迅速发展和生活方式的改变,代谢综合征(MS)的发生率急剧升高,其诊治涉及内分泌、心血管等多个学科,已成为新的健康卫生热点问题。MS代表了一系列心血管疾病危险因素的聚集状态,包括肥胖、高血压、血糖异常、致动脉粥样硬化的血脂紊乱等多种代谢异常。1988年,Reav     

Hypertension and diabetes: new therapeutic options

The treatment of high-risk hypertensive patients with diabetes presents clinicians with challenges and opportunities. The coexistence of hypertension and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications. Perhaps most important among these is the increased risk of cardiovascular events in this patient population, an observation that can be best appreciated by the increased number of deaths attributed to cardiovascular-related diseases in diabetic patients aged 45 to 65 years. Consequently, aggressive therapy in this population offers the promise of significantly reducing excess cardiovascular deaths. Despite this opportunity for reducing mortality in these high-risk patients, several challenges to treatment remain. While aggressive blood pressure reduction has been documented to reduce the rate of events in these patients, questions remain as to the level to which blood pressure should be reduced. The recent guidelines from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure emphasized the importance of treating patients with hypertension and diabetes as if they already have target organ damage. Low blood pressure targets of 130/85 mm Hg, with an optimal goal of 120/80 mm Hg, can reduce the risk of events in hypertensive patients with diabetes, regardless of the pharmacological means used. However, there are physiologic and clinical rationale for renin angiotensin system blockade, with angiotensin-converting enzyme inhibition as the preferential therapy in these patients. In this regard, preliminary data with the new class of angiotensin II receptor blockers suggest that these agents may offer benefits equivalent to those observed with angiotensin-converting enzyme inhibitors while offering better tolerance.     

Update on the metabolic syndrome: Hypertension

The presence of the metabolic syndrome identifies an individual at increased risk for diabetes, cardiovascular disease, and early mortality. However, the increased risk may vary by the absence or presence of hypertension. Current guidelines for the management of high blood pressure in the metabolic syndrome emphasize lifestyle modification as a first-line strategy. Pharmacologic treatment of elevated blood pressure in the metabolic syndrome may be necessary in the presence of other cardiovascular risk factors or to achieve adequate blood pressure control. Currently, there is no consensus as to which antihypertensive therapy should be used to treat hypertension in patients with the metabolic syndrome; it remains unclear whether achieving tight blood pressure control should outweigh the potential for development of glucose intolerance. Future research must focus on this issue given the high prevalence of the syndrome among hypertensive patients and high rates of progression to diabetes among those with the metabolic syndrome.     

Hypertension in people with Type 2 diabetes: knowledge-based diabetes-specific guidelines

The International Diabetes Federation (Europe) has updated these guidelines on hypertension management specifically in Type 2 diabetes in the light of recent results of the first prospective, randomized controlled studies to investigate clinical outcomes in people with diabetes and hypertension. The guidelines are knowledge based, i.e. based not only on evidence originating from clinical trials, but also from epidemiological and pathophysiological studies. A successful management strategy requires the following components:

• 1 Regular surveillance to detect developing hypertension and other cardiovascular (CV) risk factors.
• 2 Considering more frequent monitoring and review of CV risk factors if any single blood pressure (BP) measurement > 140/85 mmHg (or 130/75 if microalbuminuria); when appropriate, using ambulatory or home monitoring to establish the baseline BP.
• 3 Considering other CV risk factors, such as a raised albumin excretion rate, in setting the intervention threshold.
• 4 Individualizing the target BP in accordance with other CV risk factors.
• 5 Agreeing lifestyle and therapeutic interventions with the patient, with education and empowerment as required.
• 6 Implementing lifestyle modifications, including controlling calorie, salt and alcohol intake, increased physical activity, weight control and smoking cessation.
• 7 Therapeutic strategy: the primary goal of therapy is to reduce BP markedly. Combination therapy is often necessary, e.g. an angiotensin converting enzyme (ACE) inhibitor and a diuretic. Some classes are particularly useful for certain patients, notably longer-acting ACE inhibitors, angiotensin 2 receptor antagonists (A2RAs) and calcium antagonists in those at risk of diabetic nephropathy, loop diuretics and thiazides in those at risk of hyperkalaemia, β-blockers and calcium antagonists (except short-acting dihydropyridines) in patients with angina, β-blockers and ACE inhibitors after a myocardial infarction or in those with left ventricular dysfunction, and thiazide diuretics and long-acting dihydropyridine calcium antagonists for isolated systolic hypertension. A2RAs should be particularly considered when ACE inhibitors are not tolerated. α₁-Blockers should not be considered first line in the absence of outcome data. Cost of drugs will modify these strategies in developing countries.
• 8 Monitoring response to therapies and, if target levels are not achieved, either intensifying drug therapy if the CV risk justifies it, or reassessing the target.
• 9 Maintaining a quality assurance strategy.

This strategy is summarized in a simple, practical management algorithm.     

Pathophysiologic approach in genetic hypokalemia: An update

The pathophysiology of genetic hypokalemia is close to that of non-genetic hypokalemia. New molecular pathways physiologically involved in renal and extrarenal potassium homeostasis have been highlighted. A physiological approach to diagnosis is illustrated here, with 6 cases. Mechanisms generating and sustaining of hypokalemia are discussed. After excluding acute shift of extracellular potassium to the intracellular compartment, related to hypokalemic periodic paralysis, inappropriate kaliuresis (> 40 mmol/24 h) concomitant to hypokalemia indicates renal potassium wasting. Clinical analysis distinguishes hypertension-associated hypokalemia, due to hypermineralocorticism or related disorders. Genetic hypertensive hypokalemia is rare. It includes familial hyperaldosteronism, Liddle syndrome, apparent mineralocorticoid excess,11beta hydroxylase deficiency and Geller syndrome. In case of normo- or hypo-tensive hypokalemia, two etiologies are to be considered: chloride depletion or salt-wasting tubulopathy. Diarrhea chlorea is a rare disease responsible for intestinal chloride depletion. Due to the severity of hypokalemic metabolic alkalosis, this disease can be misdiagnosed as pseudo-Bartter syndrome. Gitelman syndrome is the most frequent cause of genetic hypokalemia. It typically associates renal sodium and potassium wasting, hypomagnesemia, conserved chloride excretion (> 40 mmol/24 h), and low-range calcium excretion (urinary Ca/creatinine ratio < 0.20 mmol/mmol). Systematic analysis of hydroelectrolytic disorder and dynamic hormonal investigation optimizes indications for and orientation of genotyping of hereditary salt-losing tubulopathy.     

An update on metabolic syndrome: Metabolic risk markers and adipokines in the development of metabolic syndrome

BackgroundMetabolic syndrome is a collection of physiological and biochemical abnormalities about 20–25% of adult population in developing countries is suffering from metabolic syndrome. Previous research demonstrated that adipose tissue plays an important role in energy regulation via endocrine, paracrine and autocrine signals as results of obesity due to accumulation of adipose tissue to excess that by time affects negatively both physical and psychological health and well being, it has been found that adipose tissues produces a variety of factors known as “adipokines” which play a key role in the development and progression of the disease and also hypothesized that adipokines are a possible link between obesity and the other risk components of the Metabolic syndrome. Many of the adipokines exert multiple actions in a variety of cellular processes leading to a complex array of abnormal characteristic of Metabolic syndrome. Abnormal production of these adipokines by expanded visceral fat during Adiposity contributes to a pro-inflammatory state. Increasing evidence suggests that aberrant production/release of adipokine from adipocyte i.e. adiponectin, leptin and resistin etc, may contribute to the health problems associated with Adiposity such as dyslipidemia, insulin resistance and atherosclerosis. This study conclusively have shown a significant role of adipokines secreted by adipose tissue and various metabolic risk markers play a important role in the development of Metabolic syndrome.     

南宁市老年人代谢综合征流行病学调查

目的调查南宁市老年人代谢综合征（MS）及其代谢异常组分患病情况。方法选取南宁市健康体检的60岁以上老年人2379例,依据2005年国际糖尿病联合会公布的MS新诊断标准对MS进行诊断,并进行MS组分分类。结果总的标化患病率22.5%,其中男16.2%,女33.3%；有1种以上代谢异常占91.5%,同时有2种代谢异常占32.1%。同时有3种或3种以上代谢异常29.8%。结论南宁市老年人群具有较高的MS及其相关组分的患病率。制定面向老年人MS的防治策略,以降低心脑血管并发症的发生非常必要。     

代谢综合征病人的高血压和处理

根据最新的2005国际糖尿病联盟对代谢综合征(metabolic syndrome,MS)全球共识定义[1],确认是否为代谢综合征,必须具备中心性肥胖.……     

Non-alcoholic fatty liver disease and the metabolic syndrome： An update

Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic in westernized countries, subsequently increasing the risk for developing the metabolic syndrome and nonalcoholic fatty liver disease （NAFLD）. NAFLD is estimated to affect approximate 30% of the general US population and is considered the hepatic manifestation of the metabolic syndrome. Recent findings linking the components of the metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis （NASH） will be reviewed; in particular, the role of visceral adipose tissue, insulin resistance, and adipocytokines in the exacerbation of these conditions. While no therapy has been proven effective for treating NAFLD/NASH, common recommendations will be discussed.