Diabetes mellitus and hypertension.

Diabetes mellitus and hypertension are common diseases that coexist at a greater frequency than chance alone would predict. Hypertension in the diabetic individual markedly increases the risk and accelerates the course of cardiac disease, peripheral vascular disease, stroke, retinopathy, and nephropathy. Our understanding of the factors that markedly increase the frequency of hypertension in the diabetic individual remains incomplete. Diabetic nephropathy is an important factor involved in the development of hypertension in diabetics, particularly type I patients. However, the etiology of hypertension in the majority of diabetic patients cannot be explained by underlying renal disease and remains "essential" in nature. The hallmark of hypertension in type I and type II diabetics appears to be increased peripheral vascular resistance. Increased exchangeable sodium may also play a role in the pathogenesis of blood pressure in diabetics. There is increasing evidence that insulin resistance/hyperinsulinemia may play a key role in the pathogenesis of hypertension in both subtle and overt abnormalities of carbohydrate metabolism. Population studies suggest that elevated insulin levels, which often occurs in type II diabetes mellitus, is an independent risk factor for cardiovascular disease. Other cardiovascular risk factors in diabetic individuals include abnormalities of lipid metabolism, platelet function, and clotting factors. The goal of antihypertensive therapy in the patient with coexistent diabetes is to reduce the inordinate cardiovascular risk as well as lowering blood pressure.     

Metabolic syndrome X: a review

Metabolic syndrome X is a multifaceted syndrome, which occurs frequently in the general population. It is more common in men than in women. A large segment of the adult population of industrialized countries develops the metabolic syndrome, produced by genetic, hormonal and lifestyle factors such as obesity, physical inactivity and certain nutrient excesses. This disease is characterized by the clustering of insulin resistance and hyperinsulinemia, and is often associated with dyslipidemia (atherogenic plasma lipid profile), essential hypertension, abdominal (visceral) obesity, glucose intolerance or noninsulin-dependent diabetes mellitus and an increased risk of cardiovascular events. Abnormalities of blood coagulation (higher plasminogen activator inhibitor type 1 and fibrinogen levels), hyperuricemia and microalbuminuria have also been found in metabolic syndrome X. This review summarizes the present knowledge of abnormalities in this syndrome. Each risk factor is reviewed, and potential criteria for diagnosis and therapeutic targets are discussed. Because patients with metabolic syndrome X accumulate cardiac risk factors, they should be given special attention in terms of diagnosis and treatment.     

The operative risk factors in the metabolic syndrome: Is it lipids and high BP or are there direct vascular effects of insulin resistance and obesity?

Increase in patients with central obesity and insulin resistance is an important cause for the worldwide increased incidence of type 2 diabetes. Several risk factors such as glucose intolerance, hyperinsulinemia, obesity, dyslipidemia, and hypertension, but also endothelial dysfunction and inflammation, have been found to cluster and often precede type 2 diabetes mellitus. Seeing the importance of early identification, the US National Cholesterol Education Program created a readily applicable definition of the metabolic syndrome for daily clinical practice. It is assumed that the cardiovascular risk for patients belonging to the metabolic syndrome can just be calculated out of the sum of the separate cardiovascular risk factors dyslipidemia and hypertension. However, there are also data pointing toward a higher risk than expected from these separate cardiovascular risk factors because of possible direct vascular effects of insulin resistance and obesity. Awareness of the underlying disorders of insulin resistance and its associated (non-) traditional risk factors such as endothelial dysfunction and inflammation is important for understanding the pathophysiology and thus coherent treatment.     

The insulin resistance syndrome: impact on lipoprotein metabolism and atherothrombosis

Insulin resistance is a common metabolic abnormality that is associated with an increased risk of both atherosclerosis and type 2 diabetes. The phenotype of insulin resistance includes a dyslipidemia characterized by an elevation of very low-density lipoprotein triglyceride, a reduction in high-density lipoprotein cholesterol, and the presence of small, triglyceride-enriched low-density lipoproteins. The underlying metabolic abnormality driving this dylipidemia is an increased assembly and secretion of very low-density lipoprotein particles, leading to an increased plasma level of triglyceride. Hypertriglyceridemia, in turn, results in a reduction in the high-density lipoprotein level and the generation of small, dense low-density lipoproteins; these events are mediated by cholesteryl ester transfer protein. In addition, hypertension, obesity, and a prothrombotic state are also integral components of the insulin resistance syndrome. In this review, we will provide a pathophysiologic basis, based on studies on humans and in tissue culture, for the dyslipidemia of insulin resistance. We will also review the effects of insulin resistance on the coagulation and fibrinolytic pathways. It is hoped that this review will allow health professionals better to evaluate and treat their patients with insulin resistance, thereby reducing the very much increased risk of atherosclerotic cardiovascular disease carried by these individuals.     

Microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes in the Korean population

To investigate whether microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes, we studied the association between microalbuminuria and features of insulin resistance syndrome in Korean general population. We selected 1006 subjects by a random cluster sampling among residents aged >40 years living in the Chung-Up district, a rural area of South Korea. Subjects were stratified by oral glucose tolerance status [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus], and by the presence or absence of hypertension. Urinary albumin excretion rate (UAER) was determined using timed overnight urine collection. Various cardiovascular risk factors including anthropometric indices, serum lipid, true insulin and proinsulin concentrations were also measured. The prevalence of microalbuminuria (UAER between 20 and 200 microg/min) increased as the glucose tolerance worsened (6.0% in NGT, 11.8% in IGT, and 21.8% in diabetes; chi(2) trend=25.9, P<0.001). Subjects with microalbuminuria had a higher body mass index (BMI), waist-to-hip circumference ratio (WHR), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose, fasting plasma insulin and proinsulin levels, and lower HDL-cholesterol level than subjects without microalbuminuria. In multiple regression analysis, BMI, diastolic BP, 2 h plasma glucose, and fasting plasma insulin levels were found to be independent factors associated with UAER. Multiple logistic regression analysis showed that not only diabetes mellitus and hypertension, but also fasting hyperinsulinemia and waist-to-hip ratio were independent factors associated with the presence of microalbuminuria. When the normotensive, non-diabetic subjects were analyzed separately, fasting hyperinsulinemia and impaired glucose tolerance remained independent variables associated with the presence of microalbuminuria. These results show that microalbuminuria in the Korean general population is associated with hyperinsulinemia and central obesity, and suggest that microalbuminuria is a feature of the insulin resistance syndrome independent of hypertension or type 2 diabetes.     

Diabetic dyslipidemia and pathogenesis of ischemic heart disease

BACKGROUND: Type II diabetes is associated with high risk of ischemic heart disease (IHD), diabetes and IHD have similar risk factors, abdominal obesity as well as interrelated disturbances of lipid and carbohydrate metabolism play important roles in pathogenesis of both diseases. AIM: To elucidate characteristics of metabolism and transport of lipids and carbohydrates in patients with type II diabetes and IHD with normal and excessive body mass with abdominal type of fat distribution. MATERIAL AND METHODS: Parameters of carbohydrate metabolism, blood serum levels of free fatty acids, lipid and apoprotein (apo-) parameters of lipoprotein spectrum were evaluated in subjects without diabetes or IHD (group 1), patients with IHD and normal body mass (group 2), patients with IHD combined with diabetes with normal body mass (group 3), patients with IHD, diabetes and abdominal obesity (group 4). RESULTS: Patients with combination of diabetes and IHD compared with those of groups 1 and 2 in addition to higher blood glucose had lower growth hormone, higher triglycerides, lower high density lipoprotein cholesterol (CH) and apo-A1, higher low/high density lipoprotein CH and apo-B/apo-A1 ratios. These atherogenic changes were more pronounced in patients of group 4 who had highest levels of insulin, free fatty acids, low density lipoprotein CH and apo-B and lowest glucose/insulin ratio and level of apo-A1. CONCLUSION: Insulin resistance and hyperinsulinemia are most important features of disturbed carbohydrate and lipid metabolism. Insulin resistance and hyperinsulinemia are most pronounced in subjects with abdominal obesity in whom they create conditions for impaired glucose utilization, development of atherogenic dyslipidemia and eventually emergence of IHD.     

Pathophysiology and treatment of the dyslipidemia of insulin resistance

Insulin resistance, and the compensatory hyperinsulinemia that results, has been linked to a host of defects including glucose intolerance, diabetes, hypertension, dyslipidemia, endothelial dysfunction, impaired fibrinolysis, and subclinical inflammation. Patients with this metabolic syndrome have a markedly increased risk for the development of atherothrombotic cardiovascular disease. The characteristic dyslipidemia of insulin resistance consists of elevated triglyceride and triglyceride-rich lipoprotein levels, low levels of high-density lipoprotein cholesterol, and increased concentrations of small, dense low-density lipoprotein cholesterol. Management of this dyslipidemia typically involves a dual approach. Lifestyle modification is an essential component of any successful treatment plan, but alone is usually insufficient to correct these lipoprotein abnormalities. Medications that diminish insulin resistance and directly alter lipoproteins are also necessary in the majority of cases. Combinations of therapeutic agents are often required to optimize attainment of treatment goals.     

Insulin resistance and hypertension. Patients in double jeopardy for cardiovascular disease

Essential hypertension is prevalent among older individuals, and approximately 50% of persons with hypertension can be considered to have insulin resistance and hyperinsulinemia. It appears likely that insulin resistance and hyperinsulinemia predispose to, rather than result from, hypertension. Insulin resistance is associated with abnormalities in lipoprotein metabolism, hypercoagulability, and endothelial function, which probably account in part for the increased cardiovascular risk among hypertensive patients. To identify this subset of patients, all hypertensive patients should be screened for diabetes and lipid abnormalities. The presence of impaired glucose tolerance, diabetes, or hypertriglyceridemia and low HDL suggest the presence of insulin resistance. Insulin resistant patients, in particular, will benefit from exercise and weight loss.     

Diabetes mellitus und Krebs

In type 2 diabetes mellitus (T2DM) and obesity, glucose intolerance is often accompanied by insulin resistance, hyperinsulinemia and dyslipidemia. Such patients show an increased frequency of malignancies in the liver, large bowel, pancreas, breasts and endometrium. Obesity is associated with an increased frequency of cancerous diseases even before the manifestation of diabetes. Common risk factors for cancer and abnormalities of glucose and lipid metabolism, such as unhealthy nutrition, age, smoking and too much alcohol are probably responsible. In addition, accumulating evidence suggests a direct link between an increased risk of cancer in obesity and T2DM. Hyperinsulinemia is believed to be the central player, promoting cancer incidence and progression. Antidiabetic therapy may either reduce or promote such effects by acting in an anti-insulinogenic or proinsulinogenic manner. Metformin has received much attention in this context. Especially patients with T2DM should be encouraged to subscribe to cancer prevention programs while avoiding defined risk factors.     

Fibrate Therapy in the Management of Diabetic Dyslipidemia: There is No <Emphasis Type="Italic">ACCORD</Emphasis> to be Found

Mixed dyslipidemia is a complex clinical entity that contributes significantly to the increased risk for cardiovascular morbidity and mortality that is observed in patients with type 2 diabetes mellitus. Insulin resistance is associated with reduced serum lipoprotein lipase activity, increased serum levels of very low-density lipoproteins and triglyceride, low serum high-density lipoproteins, and increased concentrations of small, dense low-density lipoproteins. Combinations of medications are frequently required in order to achieve guideline-specified goals for the various lipid fractions of diabetic patients. The fibric acid derivatives (fibrates) are effective agents for raising serum levels of high-density lipoproteins and decreasing levels of triglycerides. A number of trials have demonstrated that among patients with high triglycerides and low HDL, fibrates do beneficially impact cardiovascular morbidity in diabetic and nondiabetic individuals. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial suggests that the addition of fenofibrate to ongoing statin therapy in patients with type 2 diabetes mellitus offers limited benefit.     

TNT and Recurrent Cardiovascular Events: High-Dose Statin Therapy Offers a Lot of Bang for the Buck

Mixed dyslipidemia is a complex clinical entity that contributes significantly to the increased risk for cardiovascular morbidity and mortality that is observed in patients with type 2 diabetes mellitus. Insulin resistance is associated with reduced serum lipoprotein lipase activity, increased serum levels of very low-density lipoproteins and triglyceride, low serum high-density lipoproteins, and increased concentrations of small, dense low-density lipoproteins. Combinations of medications are frequently required in order to achieve guideline-specified goals for the various lipid fractions of diabetic patients. The fibric acid derivatives (fibrates) are effective agents for raising serum levels of high-density lipoproteins and decreasing levels of triglycerides. A number of trials have demonstrated that among patients with high triglycerides and low HDL, fibrates do beneficially impact cardiovascular morbidity in diabetic and nondiabetic individuals. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial suggests that the addition of fenofibrate to ongoing statin therapy in patients with type 2 diabetes mellitus offers limited benefit.     

Chronic insulin infusion normalizes blood pressure and the gene expressions of angiotensin II type 1 receptor in fructose-fed rats.

It remains open to debate whether hyperinsulinemia leads to the development of hypertension. We addressed this issue by investigating the effect of chronic insulin infusion on blood pressure and related parameters in hypertensive fructose-fed rats. Rats were given either normal chow or a fructose-rich diet, and insulin or saline was infused through mini-pumps in the same animals for 14 days. The chronic insulin infusion exerted no effect on the blood pressure of the chow-fed rats. Fructose feeding increased the blood pressure and levels of insulin, triglyceride and fatty acid. Insulin infusion augmented the hyperinsulinemia but normalized the blood pressure and plasma lipids. Plasma angiotensin II was elevated in the fructose-fed rats, while insulin infusion left it unchanged. The expression of angiotensin II type 1 receptor (AT1R) mRNA was doubled in both the aorta and epididymal fat of the fructose-fed rats, while that of angiotensin II type 2 receptor (AT2R) was unaltered. Insulin infusion completely rectified the over-expression of the AT1R gene. Our findings indicate that chronic insulin infusion exacerbates hyperinsulinemia while normalizing blood pressure and the gene expressions of AT1R in insulin-resistant fructose-fed rats, suggesting that endogenous hyperinsulinemia caused by insulin resistance is associated with the development of hypertension, whereas exogenous hyperinsulinemia attenuates hypertension probably due to amelioration of insulin resistance.     

糖尿病并发脑梗死的病理生理学

研究发现,糖尿病患者的脑梗死发病率显著增高且预后更差。然而,糖尿病患者的卒中危险因素极为复杂。文章从葡萄糖和脂质代谢紊乱、高血压、胰岛素抵抗和高胰岛素血症、血管舒缩功能障碍、脂联素和黏附分子表达的改变以及基因多态性等方面对该领域的研究进展进行了综述。     

Old antihypertensives and new diabetes

Diuretic antihypertensive therapy is recommended as first choice by many guidelines, often in combination with beta-blockers. However, such recommendations are based on relatively short-term trials, whereas treatment for hypertension is often a lifetime process. A meta-analysis of seven studies in 58,010 individuals, showed that the 'new' therapies, namely angiotensin-converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) provoke less new diabetes than the conventional 'old' therapies (diuretics and beta-blockers). ACE inhibitors/ARBs decreased new diabetes by 20% (P < 0.001), whereas CCBs decreased new diabetes by 16% (P < 0.001). The number needed to treat for approximately 4 years by new rather than old conventional therapy to avoid one case of new diabetes is about 60-70. Other factors contributing to increased coronary risk are increased metabolic syndrome, blood lipid changes and hypokalaemia. It is not certain whether it is the new therapy that provides protection against new diabetes or the conventional therapy that precipitates new diabetes. However, when compared with placebo, ACE inhibition by ramipril or by the ARB, candesartan, both decrease the incidence of new diabetes, raising the hypothesis that these agents actually prevent the changes leading to insulin resistance, possibly by lessening the adverse effects of angiotensin II on the endothelium. Conversely, lipid abnormalities with conventional treatment could exert adverse effects on the endothelium. Therefore endothelial changes could help to explain the benefits of 'modern' treatment compared with the defects of conventional therapy.     

Mechanisms of hepatic very low-density lipoprotein overproduction in insulin resistance

An important complication of insulin-resistant states, such as obesity and type 2 diabetes, is an atherogenic dyslipidemia profile characterized by hypertriglyceridemia, low plasma high-density lipoproteins (HDL) cholesterol and a small, dense low-density lipoprotein (LDL) particle profile. The physiological basis of this metabolic dyslipidemia appears to be hepatic overproduction of apoB-containing very low-density lipoprotein (VLDL) particles. This has focused attention on the mechanisms that regulate VLDL secretion in insulin-resistant states. Recent studies in animal models of insulin resistance, particularly the fructose-fed hamster, have enhanced our understanding of these mechanisms, and certain key factors have recently been identified that play important roles in hepatic insulin resistance and dysregulation of the VLDL secretory process. This review focuses on these recent developments as well as on the hypothesis that an interaction between enhanced flux of free fatty acids from peripheral tissues to liver, chronic up-regulation of de novo lipogenesis by hyperinsulinemia and attenuated insulin signaling in the liver may be critical to the VLDL overproduction state observed in insulin resistance. It should be noted that the focus of this review is on molecular mechanisms of the hypertriglyceridemic state associated with insulin resistance and not that observed in association with insulin deficiency (e.g., in streptozotocin-treated animals), which appears to have a different etiology and is related to a catabolic defect rather than secretory overproduction of triglyceride-rich lipoproteins.     

Pathogenesis of atherosclerosis in diabetes and hypertension

Prevalence of atherosclerotic vascular disease is markedly increased among individuals with diabetes-mellitus and hypertension. Its major clinical manifestations are consequences of atherosclerosis of coronary arteries, cerebral arteries and large arteries of lower extremities. Thus, atherosclerotic vascular disease is the major cause of mortality and significant morbidity in diabetes and hypertension. Dyslipidemia, hyperinsulinemia, and central obesity seem to be associated with increased risk of atherosclerosis, along with the development of hypertension and diabetes (NIDDM). Insulin resistance is the fundamental factor in this situation which has strong genetic predisposition. Accelerated atherosclerosis in diabetes due to mechanism unique to diabetes like non-enzymatic glycation of proteins, oxidative modification of lipoproteins, formation of lipoproteins immune complexes, lipoproteins aggregation, disturbances of cell replication and growth factors and propensity to thrombosis are clearly established. Therapeutic implication for the prevention of atherosclerosis in diabetes and hypertension clearly emphasizes the need to achieve tight control of hyperglycemia, hypertension, and hyperlipidemia in addition to avoiding cigarette smoking and developing obesity.     

Coronary artery disease risk predicted by insulin resistance, plasma lipids, and hypertension in people without diabetes

BACKGROUND: It has been shown that insulin resistance syndrome, including glucose intolerance, dyslipidemia, and hypertension, is frequently associated with coronary artery disease (CAD). However, their relative contributions and predictive power in the development of CAD are still unclear, particularly in persons without diabetes. METHOD: We examined these risk factors between 96 patients without diabetes but with angiographically documented CAD and 96 age-, sex-, and body mass index-matched healthy control subjects. Fasting plasma lipoprotein, glucose, and insulin concentrations in response to a 75-g oral glucose tolerance test were determined, and insulin sensitivity was measured by the insulin suppression test. RESULTS: Patients with CAD had significantly higher values of fasting glucose, glucose and insulin responses to oral glucose tolerance test, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride and decreased high-density lipoprotein (HDL) cholesterol concentrations compared with those of healthy people (P < 0.02-0.001). Although the steady-state plasma insulin values were similar in both groups, the steady-state plasma glucose (SSPG) concentrations were significantly higher in patients with CAD (12.2+/-0.4 versus 8.1+/-0.4 mmol/L, P < 0.001) compared with healthy subjects. When HDL < 0.9 mmol/L, LDL cholesterol > or = 4.1 mmol/L, triglyceride > or = 2.3 mmol/L, SSPG > or = 10.5 mmol/L, and presence of hypertension were defined as separate risk factors for CAD, significantly higher odds-ratio values were observed in patients with CAD compared with healthy people. From logistic multiple regression analysis, SSPG was the strongest risk, followed by lowered HDL cholesterol, elevated triglyceride and LDL cholesterol, and hypertension, to predict CAD. These 5 factors accounted for 36% of total risk for development of CAD in persons without diabetes. CONCLUSIONS: Patients without diabetes with CAD have abnormal glucose metabolism, hyperinsulinemia, and insulin resistance. Degree of insulin resistance (SSPG values), plasma lipid values, and history of hypertension together accounted for one third of all risk for CAD, although degree of insulin resistance was the strongest risk factor.     

Insulin resistance--a common link between type 2 diabetes and cardiovascular disease

Evidence suggests that diabetes and cardiovascular disease (CVD) may share an underlying cause(s), a theory known as the 'common soil' hypothesis. Insulin resistance is central both to the progression from normal glucose tolerance to type 2 diabetes and to a constellation of cardiovascular risk factors known as the metabolic syndrome. These risk factors include visceral obesity and dyslipidaemia characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridaemia and raised small dense low-density lipoprotein particle levels. Changes in adipose tissue mass and metabolism may link insulin resistance and visceral obesity, a condition that is common in type 2 diabetes. Furthermore, weight reduction, increased physical activity, metformin and acarbose have been shown to reduce the development of type 2 diabetes in genetically predisposed subjects and may decrease the high cardiovascular risk of patients with diabetes. Some fatty acid derivatives can affect energy metabolism by activating peroxisome proliferator-activated receptors (PPARs), nuclear receptors that play a key role in energy homeostasis. These receptors represent an ideal therapeutic target for reducing cardiovascular risk, because they are involved in the regulation of both insulin action and lipid metabolism. In addition to lifestyle changes, PPARgamma agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPARalpha (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events. The development of agents with both PPARalpha and PPARgamma activity promises added benefits with amelioration of insulin resistance, delayed progression to and of type 2 diabetes and a reduction of CVD.     

Type II diabetes mellitus and cardiovascular risk factors: Current therapeutic approaches

Worldwide, approximately 200 million people currently have type II diabetes mellitus (DM), a prevalence that has been predicted to increase to 366 million by 2030. Rates of cardiovascular disease (CVD) mortality and morbidity are particularly high in this population, representing a significant cost for health care systems. Type II DM patients generally carry a number of risk factors for CVD, including hyperglycemia, abnormal lipid profiles, alterations in inflammatory mediators and coagulation/thrombolytic parameters, as well as other 'nontraditional' risk factors, many of which may be closely associated with insulin resistance. Therefore, successful management of CVD associated with diabetes represents a major challenge to the clinicians. An effective way of tackling this problem is to detect the associated risk factors and to target treatment toward their improvement. Targeting hyperglycemia alone does not reduce the excess risk in diabetes, highlighting the need for aggressive treatment of other risk factors. Although the current use of statin therapy is effective at reducing low-density lipoprotein cholesterol, residual risk remains for other independent lipid and nonlipid factors. The peroxisome proliferator-activated receptor-gamma appears to be closely involved in regulating risk markers at multiple levels. A relatively new class of therapeutic agents that activate peroxisome proliferator-activated receptor-gamma, the thiazolidinedione insulin-sensitizing agents, is currently used to manage type II DM. These agents display a number of potential antiatherogenic properties, including effects on high-density lipoprotein cholesterol and triglycerides, as well as other beneficial nonlipid effects, such as regulating levels of mediators involved in inflammation and endothelial dysfunction. Research data suggest that simple strategies combining thiazolidinediones and statins could have complementary effects on CVD risk-factor profiles in diabetes, alongside the ability to control glycemia.     

Diabetes and hypertension

The incidence of hypertension is increased in individuals with diabetes mellitus. This is especially true in patients with type 2 diabetes. In these patients high blood pressure is common at the time of diagnosis of diabetes, but the development of diabetes is often preceded by a period during which hyperinsulinemia and insulin resistance is already present. Diabetes represents by itself a major risk of cardiovascular morbidity and mortality. This risk is considerably enhanced by the co-existence of hypertension. One of the main complications of type 2 diabetes is nephropathy, which manifests initially by microalbuminuria, then by clinical proteinuria, leading to a progressive chronic renal failure and end-stage renal disease. Microalbuminuria is considered today as an indicator of renal endothelial dysfunction as well as an independent predictor of the cardiovascular risk. During recent years a number of studies have shown that tight blood pressure control is essential in diabetic patients in order to provide maximal protection against cardiovascular events and the deterioration of renal function. Of note, there is recent evidence indicating that blockade of the renin-angiotensin system with angiotensin II antagonists has marked nephroprotective effects in patients with hypertension and type 2 diabetes, both at early and late stages of renal disease.