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Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.
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PMID:[Treatment of hypertension in type 2 diabetes mellitus--2002 update]. 1223 35

Insulin resistance and/or compensatory hyperinsulinemia are associated with hypertension, obesity, dyslipidemia, and glucose intolerance. Insulin resistance and hyperinsulinemia are considered to increase blood pressure through sympathetic nervous system activation, renin-angiotensin system stimulation, and vascular smooth muscle cell proliferation. Leptin, magnesium ions, nitric oxide, endothelin, peroxisome proliferator-activated receptor gamma, and tumor necrosis factor-alpha also modulate blood pressure. Decreasing insulin resistance by lifestyle modification including diet, weight loss, and physical exercise has been shown to reduce blood pressure. Angiotensin-converting enzyme inhibitors have a beneficial effect on insulin resistance. On the other hand, the angiotensin II antagonist, losartan, does not affect insulin sensitivity. The selective alpha1-blockers have a favorable metabolic profile producing increases in insulin sensitivity. A short-acting type calcium channel blocker seems to decrease insulin sensitivity. On the other hand, long-acting type calcium channel blockers improve insulin sensitivity. Thiazide diuretics and most of the beta-blockers decrease insulin sensitivity. Vasodilatory beta-blockers have been reported to improve insulin sensitivity. Use of low-dose diuretics avoids the adverse effects seen with conventional doses.
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PMID:Hypertension and insulin disorders. 1241 78

Obesity-associated hypertension is a common disease that involves a complex pathogenesis. Failure to control hypertension (HTN) in obese subjects provides a great threat to their renal and cardiovascular functions. The treatment of obesity-associated HTN is often difficult, and requires nonpharmacological and/or pharmacological approaches. Weight reduction is the cornerstone of the therapies of obesity-HTN, as it reverses the multiple components of its pathogenesis. When weight loss cannot be sustained or fails, pharmacological means should then be used. Angiotensin-converting enzyme inhibitors (ACEI) are the drug of choice: they can reduce blood pressure, protect the kidney and heart, and improve the metabolic abnormalities in obese subjects. Angiotensin-2 type-1 receptor blockers have a renoprotective benefit similar to ACEI, and they provide an important alternative to the use of ACEI. Diuretics are very effective in African-American obese hypertensives, but small doses should be used to avoid adverse effects on metabolic profiles. Long-acting calcium channel blockers are also effective and have the advantage of no adverse metabolic effects. Nondihydropyridine calcium channel blockers may provide additional renal and cardiovascular protective effects. The beta-adrenergic receptor blockers can cause further weight gain and metabolic abnormalities in obese subjects; therefore, careful monitoring is needed. There are few clinical data that support the efficacy and benefit of centrally acting alpha-2 agonists and alpha-adrenergic receptor antagonists in the treatment of obesity-HTN.
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PMID:Renal and cardiovascular considerations for the nonpharmacological and pharmacological therapies of obesity-hypertension. 1252 62

The drug treatment of chronic coronary insufficiency in diabetic patients is now well defined. Platelet antiaggregants, especially aspirin, must be prescribed in the long-term or even indefinitely. Other drugs (beta-blockers, calcium channel blockers, nitrates, etc.) can be used in the same way as in the absence of diabetes. Angioplasty gives immediate favourable results in diabetics, very similar to those obtained in the absence of diabetes. In contrast, the longer term prognosis is less favourable, as the mortability, myocardial infarction, restenosis and bypass graft rates are significantly higher. First-line stenting lowers the restenosis rate to a level comparable to that observed in non-diabetics. However, instrumental revascularization is less complete than surgical revascularization and the number of redilatations and/or secondary bypass grafts remains high. The indications, mortality and early complications of coronary surgery are now identical to those observed in the absence of diabetes. Its long-term results are significantly more favourable than those of medical treatment or even angioplasty, although this issue is still controversial. The improved prognosis observed in operated diabetic coronary patients is due to the more frequent use of arterial bypass grafts. The maintenance of blood glucose control and correction of the frequently associated cardiovascular risk factors (obesity, sedentary lifestyle, smoking, HT, dyslipidaemia) increase the efficacy of treatment of coronary insufficiency in diabetic patients. This goal can only be achieved by permanent, unfailing collaboration between cardiologists and diabetologists.
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PMID:[Treatment of coronary insufficiency in diabetics. Part 3: chronic coronary insufficiency]. 1255 83

In light of the increasing prevalence, morbidity, and mortality of heart failure, effective preventative strategies are urgently needed. Risk factors for heart failure include coronary artery disease and other atherosclerotic vascular diseases, hypertension, diabetes, renal insufficiency, obesity, and family history of cardiomyopathy. Essential strategies for prevention of heart failure are modification of risk factors for heart failure development; comprehensive hypertension, atherosclerosis, and diabetes treatment; and detection and treatment of asymptomatic left ventricular dysfunction. The B-type natriuretic peptide assay may aid in identifying asymptomatic left ventricular dysfunction in patients with risk factors for heart failure. In patients with hypertension, atherosclerosis, and/or diabetes, angiotensin-converting enzyme inhibitor, beta-blocker, aspirin, and statin therapy can prevent progression to symptomatic heart failure. Avoidance of calcium channel-blockers as first-line antihypertensive therapy can also reduce the risk of heart failure. There remain substantial opportunities to improve implementation of therapies proven to prevent heart failure in the large number of patients at risk.
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PMID:Prevention of heart failure: effective strategies to combat the growing epidemic. 1268 99

Long-term hypertension contributes to significant cardiovascular and renal morbidity and mortality. Although chronic hypertension is much rarer in the adolescent population than in adults, identifying the hypertensive adolescent and intervening with risk factors such as obesity that may promote hypertension is important for the clinician treating adolescents. Since both primary and secondary causes of hypertension may exist in the adolescent, a thorough and sequential clinical and diagnostic evaluation must be undertaken, including screening urinalysis, blood chemistries, and renal sonography. There are pitfalls in interpreting casual blood pressure measurements in adolescents, and the role of ambulatory blood pressure monitoring is evolving. Lifestyle modifications, including diet, exercise, and limitation of sodium intake, remain the foundation of treatment. Commonly used medications include calcium channel blockers, angiotensin receptor blockers and converting enzyme inhibitors, beta blockers, and diuretics. When considering medication in the hypertensive adolescent, potential complications of therapy must be reviewed in light of the physical and psychosocial changes ongoing in this age group.
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PMID:Hypertension in adolescents: a review of diagnosis and management. 1289 Oct 48

Cardiovascular diseases (CVD) are the major causes of mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of CVD. The incidence of hypertension in patients with diabetes is approximately twofold higher than in age-matched subjects without the disease, and conversely, individuals with hypertension are at increased risk of developing diabetes compared with normotensive persons. Furthermore, because up to 75% of cases of CVD in patients with diabetes can be attributed to hypertension, aggressive management of elevated blood pressure (BP) (ie, to <130/85 mm Hg) in these patients is essential for reduction in cardiovascular morbidity and mortality. The renin-angiotensin system is an important regulator of both BP and obesity, and its pharmacologic modulation may thus translate into significant cardiovascular benefits. Apart from hypertension and obesity, the important risk factors for CVD in patients with diabetes include atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, and coagulation abnormalities. Therefore, effective prevention of major cardiovascular events in patients with diabetes requires combination therapy with agents that target key factors contributing to cardiovascular morbidity and mortality. The antiplatelet and anti-inflammatory effects of aspirin, the lipid-lowering activity of statins, as well as the antihypertensive effects of various agents (eg, diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers) have all been demonstrated to provide substantial reductions in cardiovascular events.
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PMID:Recommendations for special populations: diabetes mellitus and the metabolic syndrome. 1523 87

The management of hypertension in the overweight and obese patient is a frequently encountered but under investigated clinical problem. The conventional management of such patients involves weight reduction with dietary therapy or a combined approach with dietary and anti-obesity drug therapy. However, long-term weight reduction, which is necessary to sustain blood pressure (BP) control, is not feasible in over 80% of patients. Anti-obesity therapy with orlistat has inconsistent effects on BP and may benefit only patients who have uncontrolled or non-medicated hypertension. Anti-obesity therapy with sibutramine may be associated with a modest worsening of BP control. Consequently, antihypertensive drug therapy is often required to supplement a weight reduction programme, and also in patients with severe hypertension or hypertension-associated end-organ damage. Treatment with a thiazide diuretic should be considered as first-line antihypertensive drug therapy in overweight and obese patients. ACE inhibitors or non-dihydropyridine calcium channel antagonists are reasonable alternatives where clinically indicated, or they can be used in combination with a thiazide diuretic if treatment with the diuretic alone is insufficient. If such treatment is inadequate for BP control, the addition or substitution of an alpha- or beta-adrenoceptor antagonist may be considered, although the latter can be associated with weight gain. Concurrent disease is an important determinant of first-line and supplementary antihypertensive drug therapy. Additional studies are needed to determine the long-term (>1 year) efficacy and safety of antihypertensive and anti-obesity management strategies in the overweight and obese hypertensive patient.
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PMID:The management of hypertension in the overweight and obese patient: is weight reduction sufficient? 1516 30

Recent trials have suggested that inhibitors of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), may reduce the incidence of new-onset diabetes in patients with or without hypertension and at high risk of developing diabetes. In this review, we critically evaluate the evidence from recent clinical trials for such a potential preventive effect of ACE inhibitors and ARBs, including a meta-analysis of these recent trials. The reduced incidence of diabetes in patients at high risk of developing diabetes by ACE inhibitors or ARBs has been explained by haemodynamic effects, such as improved delivery of insulin and glucose to the peripheral skeletal muscle, and non-haemodynamic effects, including direct effects on glucose transport and insulin signalling pathways, all of which decrease insulin resistance. There is now evidence that the pancreas may contain an in situ active RAS, which appears to be upregulated in an animal model of type 2 diabetes. Thus, ACE inhibitors and ARBs may act by attenuating the deleterious effect of angiotensin II on vasoconstriction, fibrosis, inflammation, apoptosis and beta-cell death in the pancreas, thereby protecting a critical beta-cell mass essential for insulin production. New evidence is presented that ACE inhibitors and ARBs may delay or prevent the development of insulin resistance and diabetes, for which novel mechanisms are suggested. The actions of agents that interrupt the RAS on insulin resistance, obesity and diabetes warrant further investigation in other animal models. Prospective clinical studies with the primary endpoint of the prevention of diabetes are now indicated to (i) further explore whether the inhibitors of the RAS are superior compared to other antihypertensive agents such as calcium channel blockers (CCBs) and (ii) to evaluate the potential beneficial effects of combination antihypertensive regimens on the development of diabetes.
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PMID:Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. 1571 83

The association between obesity and hypertension is well known. The hemodynamic features of obesity-related hypertension are an expansion of extracellular volume inducing hypervolaemia and increased cardiac output, with activation of both the sympathetic nervous system and the renin--angiotensin system. It is suggested that obesity-related hypertension may be considered as a subset of essential hypertension, and treated as an identity. Orlistat and sibutramine both reduce body weight in the obese patients. The use of orlistat in obese hypertensive patients is associated with a small decrease in blood pressure, whereas sibutramine may increase the blood pressure. Thus, orlistat may be preferred in the obese hypertensive patients. Diuretics and beta-blockers decrease insulin sensitivity, which is an unwanted effect in obesity, and should be used with caution in obese hypertensive patients. The calcium channel blockers have no or minor effects on insulin sensitivity and may be considered for use in obese hypertensive patients. Inhibitors of the effects of angiotensin may be the antihypertensive drugs of choice for obese hypertensive patients, as in addition to reducing blood pressure, ACE inhibitors and AT(1) receptor antagonists have no effect or improve insulin sensitivity, and are renoprotective. More clinical trials are needed for the centrally acting antihypertensives (clonidine, rilmenidine) in obese hypertensive patients, as they inhibit the sympathetic nervous and renin--angiotensin systems, which are overactive in this population.
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PMID:Clinical evidence for drug treatments in obesity-associated hypertensive patients--a discussion paper. 1583 64


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