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Major clinical trials have shown that excellent glycemic control, sustained over time, can prevent or delay the microvascular complications of diabetes, including retinopathy, nephropathy, and neuropathy. No prospective trial has clearly shown that glycemic intervention can prevent the macrovascular complications of diabetes, such as myocardial infarction, cerebrovascular accident, and amputation. However, a number of landmark clinical trials have shown the efficacy of control of blood pressure and lipids and use of antiplatelet agents (mainly aspirin) in protecting the macrovasculature of individuals with diabetes. In this article, glycemic, blood pressure, lipid, and antiplatelet trials relevant to the treatment of people with type 2 diabetes are reviewed.
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PMID:Clinical trial evidence for cardiovascular risk reduction in type 2 diabetes. 1180 66

Patients with diabetes exhibit a high incidence of diabetic cardiomyopathy and vascular complications, which underlie the development of retinopathy, nephropathy, and neuropathy and increase the risk of hypertension, stroke, and myocardial infarction. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the development of endothelial dysfunction in a streptozotocin-induced model of diabetes. We investigated the role of PARP activation in the pathogenesis of cardiac dysfunction in streptozotocin-induced and genetic (nonobese diabetic) models of diabetes in rats and mice. Development of diabetes was accompanied by hyperglycemia, cardiac PARP activation, a selective loss of endothelium-dependent vasodilation in the thoracic aorta, and an early diastolic dysfunction of the heart. Treatment with a novel potent phenanthridinone-based PARP inhibitor, PJ34, starting 1 week after the onset of diabetes, restored normal vascular responsiveness and significantly improved cardiac dysfunction, despite the persistence of severe hyperglycemia. The beneficial effect of PARP inhibition persisted even after several weeks of discontinuation of the treatment. Thus, PARP activation plays a central role in the pathogenesis of diabetic cardiovascular (cardiac as well as endothelial) dysfunction. PARP inhibitors may exert beneficial effects against the development of cardiovascular complications in diabetes.
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PMID:The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. 1181 63

1. Diabetes is a major global public health problem. The prevalence of this disease is predicted to increase sharply in the coming decades, particularly in less-developed regions of the world. 2. Most premature morbidity and mortality associated with diabetes relates to markedly increased risks of major cardiovascular diseases, such as myocardial infarction and stroke (macrovascular events), as well as microvascular complications, such as nephropathy and retinopathy. 3. Hypertension is a prevalent and important risk factor for vascular events in these patients. However, observational data demonstrate a continuous relationship between blood pressure and risk of vascular events, suggesting that even those individuals considered normotensive may benefit from blood pressure lowering. 4. Trials of blood pressure lowering among mostly hypertensive individuals with diabetes have demonstrated benefit of intervention on macrovascular and microvascular outcomes. Recent data may suggest additional effects of angiotensin- converting enzyme inhibitors independent of blood pressure lowering. 5. Issues where data are lacking with respect to blood pressure lowering in diabetes include the effects of blood pressure lowering among non-hypertensive individuals and the effects of blood pressure lowering regimens based on different classes of drug. 6. Data expected to address some of these issues are being collected. These include a prospective meta-analysis of blood pressure-lowering trials with large numbers of patients with diabetes. A new large-scale randomised trial, ADVANCE (Action in Diabetes and Vascular Disease), is also described.
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PMID:Blood pressure lowering in diabetes: a brief review of the current evidence and description of a new trial. 1190 27

Type 2 diabetes is associated with the increased risk of microvascular and macrovascular complications. The aim of this study was to determine risk factors for the development of long-term complications of Type 2 diabetes. We analyzed medical records of all patients, who came with newly diagnosed Type 2 diabetes to one regional outpatient diabetes clinic from 1980 to 1994 (n=2175). The data, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure and body mass index (BMI), were assessed. Also, the time from the diagnosis of Type 2 diabetes to the occurrence of complications was obtained. Using the regression model in the survival analysis, we examined which of the risk factors determined the rate of the development of nephropathy, proliferative retinopathy, cardiovascular disease and stroke. Patients with higher fasting plasma glucose and higher mean blood pressure had higher risk of developing nephropathy and proliferative retinopathy. Higher mean arterial blood pressure was associated with higher rate of stroke and cardiovascular disease. High total cholesterol increased the hazard of coronary artery disease and proliferative retinopathy. In conclusion, blood pressure and fasting plasma glucose are major risk factors for microvascular complications in Type 2 diabetes. An increased blood pressure determined the macrovascular complications in Type 2 diabetes, but the effect of increased fasting plasma glucose could not be proved.
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PMID:Risk of macrovascular and microvascular complications in Type 2 diabetes: results of longitudinal study design. 1212 85

In people who are healthy, circadian rhythm in blood pressure is well established, with a 10% to 20% decrease in systolic and diastolic blood pressure during nighttime. Deviations correlate with target organ disease such as left ventricular hypertrophy, retinopathy, renal disease, and stroke. Little is known about blood pressure and circadian patterns in stroke patients. This study examined 13 patients hospitalized after ischemic stroke and monitored 24-hour blood pressure with ambulatory blood pressure monitors programmed tocollect readings every 30 minutes. All subjects had an abnormal pattern in blood pressure that did not dip during nighttime. Blood pressure load, a reported indicator of risk for target organ damage, was exceeded in all subjects during daytime and nighttime. Thus stroke patients are at high risk for target organ disease including recurrent stroke. Hypertensive management of stroke patients requires further investigation.
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PMID:Twenty-four-Hour blood pressure variability after acute ischemic stroke. 1221 32

Many types of adverse ocular reactions to oral contraceptives (OCs) have been reported, but the role of OCs has not always been confirmed. Neuroophthalmologic complications may result from cerebral vascular accidents responsible for visual field deficits, accidents affecting the cerebral trunk, ischemic accidents resulting from obstruction of the internal carotid artery. The role of OCs in cerebral vascular accidents is controversial. Most reports concern older formulations containing high doses of estrogen. In the current state of knowledge it is generally agreed that OCs may induce an increased thromboembolic risk in women over 35, those who smoke, and those with risk factors for atherosclerosis. It is agreed that occurrence of a transient ischemic cerebral vascular accident requires immediate termination of OC use. OCs have been implicated occasionally in retrobulbar optic neuropathy, but the condition in young women appears more likely to be the 1st manifestation of a sclerosis. OCs appear to increase the incidence of benign intracranial hypertension, manifested by headaches, papillary edema endangering the optic nerve, and the absence of visible anomalies on the scanner. It is also recognized that migraines are induced or aggravated by OCs. Migraines are known to be linked to hormonal factors. Ophthalmic migraines belong to the subgroup of vascular migraines. Retinal vascular diseases such as occlusion of the central retinal artery, intraocular hemorrhage, and more rarely macular edema have been reported retrospectively but their documentation has been insufficient to permit determination of causality. The prognosis for retinal emboli is mediocre. Problems in color vision initially affecting blue have been described in OC users and may be a function of the duration of use. The condition is especially prevalent in diabetes. Pregnancy appears to accelerate the loss of visual field in some women with pigmentary retinopathy. For that reason some ophthalmologists recommend that they avoid OCs. Other ocular problems have been observed in OC users but no link has been proven and the only evidence is anecdotal. It has been suggested that OCs decrease tolerance for contact lenses, but prospective studies have not demonstrated a link. All contraindications to OC use should be scrupulously respected. Use should be terminated immediately in case of transient ischemic accident, appearance of sudden severe headaches, vertigo, or vision problems such as papillary edema or retinal hemorrhage.
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PMID:[Adverse ocular reactions to oral contraceptive use]. 1231 84

Stroke is a major cause of morbidity and mortality. Full assessment of stroke or transient ischaemic attack (TIA) patients is required to identify all risk factors and apply appropriate secondary preventative strategies. Antiplatelet therapies are effective in the secondary prevention of ischaemic stroke and can be justified despite adverse effects such as gastrointestinal haemorrhage. Aspirin (acetylsalicylic acid), aspirin plus dipyridamole, ticlopidine and clopidogrel are all of value but their adverse effect profiles vary significantly. Combinations of antiplatelet agents may offer additional benefit but not all combinations have been studied in stroke patients. Anticoagulation with agents such as warfarin is effective with coexisting atrial fibrillation and other conditions predisposing to cardioembolic stroke. Antihypertensive agents have been extensively studied in the primary prevention of stroke; however, relatively few trials of antihypertensive agents in the secondary prevention of stroke are available. The incidence of adverse effects of antihypertensive agents is relatively low and the benefit-risk profile would tend to favour their use in the secondary prevention of stroke. Recent studies of ACE inhibitors have identified an important role for these agents in the secondary prevention of stroke even in those who are normotensive and in those who have had a haemorrhagic stroke. The incidence of serious adverse effects with ACE inhibitors appears relatively low. Lipid-lowering agents may have a role to play in certain groups of patients with stroke. The incidence of adverse effects is relatively low with HMG-CoA reductase inhibitors. Cigarette smoking is an important risk factor for stroke and evidence is available that smoking cessation does reduce the individual's risk of stroke. Pharmacological agents are available to help smoking cessation. In patients with diabetes mellitus, intensive regimens with insulin and oral hypoglycaemic agents have so far not definitively been shown to reduce the incidence of macrovascular complications such as stroke. Tight glycaemic control has been shown to improve microvascular complications such as retinopathy, nephropathy and neuropathy and hence this is reason enough to advocate the use of these agents. Future developments in the treatment of diabetes may help. Secondary prevention of stroke has improved greatly over the past decade and hopefully will continue to improve. The use of pharmacological agents available currently and in the future will be clarified and refined as further clinical trials report.
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PMID:A benefit-risk assessment of agents used in the secondary prevention of stroke. 1238 Dec 15

Diabetes is the singlemost important metabolic disease which can affect nearly every organ system in the body. It has been projected that 300 million individuals would be affected with diabetes by the year 2025. In India it is estimated that presently 19.4 million individuals are affected by this deadly disease, which is likely to go up to 57.2 million by the year 2025. The reasons for this escalation are due to changes in lifestyle, people living longer than before (ageing) and low birth weight could lead to diabetes during adulthood. Diabetes related complications are coronary artery disease, peripheral vascular disease, neuropathy, retinopathy, nephropathy, etc. People with diabetes are 25 times more likely to develop blindness, 17 times more likely to develop kidney disease, 30-40 times more likely to undergo amputation, two to four times more likely to develop myocardial infarction and twice as likely to suffer a stroke than non-diabetics. Lifestyle modifications, inclusive of dietary modification, regular physical activity and weight reduction are indicated for prevention of diabetes.
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PMID:Epidemiology of diabetes in India--current perspective and future projections. 1240 71

Systemic hypertension is a common condition associated with significant morbidity and mortality. Hypertension confers cardiovascular risk by causing target-organ damage that includes retinopathy in addition to heart disease, stroke, renal insufficiency and peripheral vascular disease. The recognition of hypertensive retinopathy is important in cardiovascular risk stratification of hypertensive individuals. This review reevaluates the changing perspectives in the pathophysiology, classification and prognostic significance of fundal lesions in hypertensives.
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PMID:Hypertension and the eye: changing perspectives. 1242 Jan 90

For patients with diabetes mellitus (DM), chronic complications can be devastating. Cardiovascular illness, the major cause of morbidity and mortality among these patients, encompasses macrovascular disease, with heart attacks, strokes, and gangrene; and microvascular disease, with retinopathy, nephropathy, and neuropathy (somatic and autonomic). Macrovascular events occur earlier in individuals with DM than in people without DM, and the underlying pathologies are often more diffuse and severe. Diabetic arteriopathy, which encompasses endothelial dysfunction, inflammation, hypercoagulability, changes in blood flow, and platelet abnormalities, contributes to the early evolution of these events. Efforts are under way to determine interventions that may have the potential to prevent or halt the complications of DM. Tight glucose and blood pressure (BP) control is known to improve the vascular status of patients with DM by varying degrees. Use of anti-inflammatory drugs and lowering low-density lipoprotein cholesterol (LDL-C) levels are also useful. An emerging understanding of the importance of small, dense LDL-C and the anti-inflammatory effects of statins has provided new algorithms for primary prevention of macrovascular disease. Antiplatelet agents have also been shown to be effective in the secondary prevention of cardiovascular events. In the ideal world every risk factor would be addressed and each person with DM would have excellent glycemic control, low to normal BP, and a low LDL level, and would be taking an angiotensin-converting enzyme (ACE) inhibitor, together with a statin, aspirin, and clopidogrel. Under these near-perfect conditions, the emerging epidemic of macrovascular disease could be contained. Microvascular disease, however, is a consequence of hyperglycemia. For every 1% reduction in glycosylated hemoglobin it is possible to achieve a 22% to 35% reduction in the microvascular complications. BP control is vital and the liberal use of ACE inhibitors and angiotensin receptor blockers to slow the progression of renal disease should drastically reduce the incidence of blindness, dialysis, and amputations. This article provides an overview of prevention of macrovascular disease such as stroke, myocardial infarction, and peripheral arterial disease and microvascular complications such as retinopathy, nephropathy, and neuropathy in patients with DM.
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PMID:Prevention of the complications of diabetes. 1265 55


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