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Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.
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PMID:Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus. 1154 17

Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.
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PMID:Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. 1243 44

The most common and clinically important complication in adults with diabetes is cardiovascular disease (CVD), which includes coronary heart disease, peripheral vascular disease, and stroke. Both type 2 diabetes and the insulin resistance syndrome are associated with a marked increase in the risk for CVD. The metabolic syndrome and the closely related insulin resistance syndrome have recently been recognized as important disorders, each being associated with an increase in CVD risk even in the absence of glucose intolerance. Given the significant public health burden of CVD, risk reduction has emerged as a significant clinical challenge for most practitioners. Diabetes and the insulin resistance syndrome are closely related disorders, with insulin resistance being more than a key pathogenic defect in type 2 diabetes. Even in the absence of glucose intolerance, these 2 disorders are both associated with a number of distinct pathologic findings, including hypertension, atherogenic dyslipidemia, a prothrombotic environment, and significant vascular and hemodynamic abnormalities that result from endothelial cell dysfunction. Insulin resistance is now recognized to be closely associated with the development of each of these risk factors. This article uses a case-based approach to discuss the unique features of insulin resistance and type 2 diabetes considered to be key contributors to CVD risk. A systematic approach to both evaluation and management is proposed, with priority given to therapies of demonstrated clinical benefit. Because of its critical and central role in the development of many CVD risk factors, targeted treatment of insulin resistance will also be discussed as such therapy may prove to be a critical component of care in years to come.
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PMID:The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance. 1251 Jul 88

The prevalence of marked obesity is increasing rapidly among adults and has more than doubled in 10 years. Sixty-one percent of the adult population of the United States is overweight or obese. Americans are the fattest people on earth. Paradoxically these increases in the numbers of persons who are obese or overweight have occurred during recent years when Americans have been preoccupied with numerous dietary programs, diet products, weight control, health clubs, home exercise equipment, and physical fitness videos, each "guaranteed" to bring rapid results. Overweight and obesity are also world problems. The World Health Organization estimates that 1 billion people around the world are now overweight or obese. Westernization of diets has been part of the problem. Fruits, vegetables, and whole grains are being replaced by readily accessible foods high in saturated fat, sugar, and refined carbohydrates. Since class 3 obesity (morbid or extreme obesity) is associated with the most severe health complications, the incidence of hypertension, stroke, heart disease, diabetes, and peripheral vascular disease will increase substantially in the future. Recently, obesity alone has been implicated in the development of cardiac hypertrophy and CHF. The metabolic syndrome associated with abdominal obesity, which includes insulin resistance, dyslipidemia, and elevated CRP levels, identifies subjects who have an increase in cardiovascular morbidity and mortality. Twenty to 25% of the adult population in the United States have the metabolic syndrome, and in some older groups this prevalence approaches 50%. The prevalence of overweight children in the United States has also been increasing dramatically, especially among non-Hispanic blacks and Mexican-American adolescents. Overweight children usually become overweight adults. Atherosclerosis begins in childhood. The degree of atherosclerotic changes in children and young adults can be correlated with the presence of the same risk factors seen in adults. As health providers, our direction is obvious!
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PMID:Obesity and the metabolic syndrome. 1262 76

Patients with end-stage renal disease (ESRD) are at extreme cardiovascular risk. At least half of all patients starting dialysis therapy have overt cardiovascular disease (CVD). In addition, recent studies suggest annual incidence rates for new-onset cardiac failure, peripheral vascular disease, ischemic heart disease (IHD), and stroke of approximately 7%, 7%, 5%, and 1%, respectively. High-level exposure to traditional risk factors, such as smoking and dyslipidemia, hemodynamic overload factors, such as anemia and hypertension, and a myriad of metabolic factors related to uremia are all likely to play a role. There has been explosive growth in observational studies and a heartening, if less dramatic, increase in risk factor intervention trials, suggesting that risk factor modification can lead to meaningful benefit.
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PMID:Clinical epidemiology of cardiac disease in dialysis patients: left ventricular hypertrophy, ischemic heart disease, and cardiac failure. 1264 74

Cardiovascular disease post-transplant, particularly ischemic heart disease, is a significant problem for all transplant recipients. The major risk factors-smoking, obesity, diabetes, dyslipidemia and hypertension-are often more prevalent in heart transplant populations than in the general population. One of the main risk factors influencing graft loss and patient survival is cardiac allograft vasculopathy (CAV). Because CAV affects between 30% and 60% of cardiac transplant recipients within 5 years of surgery, prevention is a key focus for cardiac transplant teams today. CAV is caused by both immunologic mechanisms (e.g., acute rejection and anti-HLA antibodies) and non-immunologic mechanisms relating to the transplant itself or the recipient (e.g., donor age, hypertension, hyperlipidemia and pre-existing diabetes) or to the side effects often associated with immunosuppression with calcineurin inhibitors or corticosteroids (e.g., cytomegalovirus infection, nephrotoxicity and new-onset diabetes after transplantation). The calcineurin inhibitors, cyclosporine and tacrolimus, effectively prevent acute rejection, but do not prevent the development of CAV. CAV prevention will require a combined approach of new adjunct immunosuppressant agents (e.g., the proliferation signal inhibitors) and reduction in cardiovascular risk. Hypertension, hyperlipidemia and diabetes are also associated with the immunosuppression required to prevent organ rejection. Some studies have shown that hypertension is present more frequently in cyclosporine-treated patients than in tacrolimus-treated patients and that tacrolimus may be associated with a more favorable lipid profile. On the other hand, tacrolimus may be more diabetogenic than cyclosporine with current data suggesting a trend but no statistically significant supporting evidence. New-onset diabetes after transplantation is at times difficult to manage and may be an important determinant along with hypertension and hyperlipidemia of ischemic heart disease, cerebrovascular disease and peripheral vascular disease. The choice of calcineurin inhibitor for an immunosuppressive regimen in heart transplantation should consider the associated relative cardiovascular risks.
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PMID:Cardiac allograft vasculopathy after heart transplantation: risk factors and management. 1509 4

The causal relationship between dyslipidemia and atherosclerosis is well-documented. Screening and appropriate management of dyslipidemia by health care providers is imperative in both primary and secondary prevention of coronary artery disease, peripheral vascular disease, and stroke. In response to the release of new research data, clinical practice guidelines for the management of dyslipidemia in Canada have recently been updated. This article will provide an overview of the recommendations for screening, risk assessment, and target lipid values. Dietary and lifestyle interventions will be discussed in addition to pharmacotherapy as management strategies for achieving therapeutic lipid targets.
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PMID:Clinical practice guidelines for the management of dyslipidemia. 1523 23

The number of people with diabetes grows worldwide. The complications resulting from this disease are a significant cause of morbidity and mortality. World Health Organization estimates that, while in the year 2000 the number of people with diabetes was about 177 million, by 2025, this will increase to at least 300 million. The diabetes epidemic, without primary prevention, will continue to grow. Individuals with type 2 diabetes are at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke, and they have a greater probability of having hypertension, dyslipidemia, and obesity. A number of clinical trials provide evidences that RAAS inhibition could be helpful at preventing new onset of type 2 diabetes mellitus. Pharmacologic treatment that antagonize the renin-angiotensin system (RAS) provide more benefits, not only in patients after myocardial infarction and in congestive heart failure, but also in persons with hypertension and type 2 diabetes mellitus.
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PMID:Renin-Angiotensin-Aldosterone system inhibition in prevention of diabetes mellitus. 1552 18

Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.
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PMID:Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. 1633 Oct 93

Diabetes mellitus is associated with a greater risk of developing atherosclerosis and its complications: stroke, myocardial infarction, and peripheral vascular disease. In patients with diabetes, atherosclerosis represents a complex multifactorial disease with increased lesion progression and severity compared to the nondiabetic population. Several risk factors have been proposed to explain the increased risk of cardiovascular disease with diabetes. They include: hyperglycaemia, dyslipidemia, accelerated formation of advanced glycation end-products (AGEs), increased oxidative stress, and genetic factors. It is difficult to precisely establish the elements leading to diabetes-accelerated atherosclerosis by means of epidemiological studies because all these factors coexist in diabetic patients. Thus, diabetic animal models that reproduce exacerbation of atherosclerosis would be helpful to understand why atherosclerosis is accelerated by diabetes, and to design appropriate treatments to limit its progression. This review analyzes most of the animal models developed to reproduce diabetes-accelerated atherosclerosis, and summarizes the effects of hyperglycaemia and lipid abnormalities on atherogenesis.
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PMID:Role of diabetes in atherosclerotic pathogenesis. What have we learned from animal models? 1652 83


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