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 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult male rats were maintained for 10 days on a standard chow diet or that diet supplemented with either safflower or marine fish oils, and then rendered diabetic with streptozotocin (40 mg/kg of body weight) and circulating metabolites determined over the next 3 days. Pre-diabetic concentrations of glucose and insulin did not differ between groups, and the severity of hyperglycaemia and lowering of insulin in streptozotocin-treated animals were also similar. Pre-diabetic concentrations of plasma free fatty acids and triacylglycerols were lower, and blood ketone bodies were higher in non-diabetic rats fed fish oil than in both other groups. However, following streptozotocin treatment, plasma free fatty acids rose significantly more in both groups of oil-fed animals than in chow-fed ones. Plasma triacylglycerols were unaltered from pre-treatment levels in rats fed chow, but rose considerably in both groups fed oil-supplemented diets. In a subsequent experiment it was shown that the increase in triacylglycerols persisted for up to 11 days after streptozotocin and the hypertriglyceridaemia was greatest in the fish oil group. The rise would seem to result from defective clearance of lipoproteins of dietary origin. It appears that fish oil-supplemented diets should be avoided in diabetics until the possibility of increased hypertriglyceridaemia has been excluded by controlled studies.
Atherosclerosis 1986 Mar
PMID:Time-course of changes in plasma lipids in diabetic rats fed diets high in fish or safflower oils. 351 64

Occlusion of the internal carotid or middle cerebral artery was seen in 44 young adults of both sexes from a rural population in Ceylon over a period of four years. None had hypertension, diabetes, prediabetes, or hypercholesterolaemia. There were 19 men with internal carotid occlusions, most being due to atherosclerotic thrombosis. The high incidence of atherosclerosis in these patients on a marginal diet remains an enigma, and we suggest that carbohydrate-induced hyperlipidaemia might be an important aetiological factor. There were 13 men with middle cerebral occlusions, the aetiology of which remains obscure. Occult embolism or atherothrombosis are suggested as possible causative factors. Of the 12 women five had middle cerebral artery occlusions in the last trimester of pregnancy and two had internal carotid artery occlusions in the puerperium. The pattern of ischaemic strokes in women aged 15-45 was similar to that observed in Western countries, though our patients differed ethnologically and in dietary habits.
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PMID:Strokes in young adults. 507 49

Obesity and Type 2 diabetes are now major public health issues in developed nations and have reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican-Americans, African-Americans, and Australian Aborigines. These groups all show hyperinsulinemia and insulin resistance, which have been demonstrated to be future predictors of Type 2 diabetes and have also been suggested as key factors in the etiology of the Metabolic Syndrome. It is now increasingly recognized that Type 2 diabetes is part of a cluster of cardiovascular disease (CVD) risk factors comprising the Metabolic Syndrome. This group is at very high risk of atherosclerosis because each of the risk factors in the Metabolic Syndrome cluster in its own right is an important CVD risk factor. They also contribute cumulatively to atherosclerosis. A key strategy in reducing macrovascular disease lies in the better understanding of the Metabolic Syndrome--glucose intolerance, hypertension, hyperlipidemia, and central obesity. Although it has been suggested that hyperinsulinemia/insulin resistance is the central etiological factor for the Metabolic Syndrome, epidemiological data do not support the idea that this can account for all of the cluster abnormalities. We have animal and human data suggesting that hyperleptinemia rather than, or synergistically with, hyperinsulinemia may play a central role in the genesis of the CVD risk factor cluster that constitutes the syndrome. Studies in Psammomys obesus (the Israeli sand rat) suggest hyperinsulinemia/insulin resistance is an early metabolic lesion in the development of obesity and Type 2 diabetes. This animal also develops other features of the Metabolic Syndrome, making it an excellent model to investigate etiology. Psammomys, when placed on an ad libitum laboratory diet, develops hyperinsulinemia, insulin resistance, impaired glucose tolerance, diabetes, and dyslipidemia. It also develops hyperleptinemia and leptin insensitivity, and hyperleptinemia is correlated with insulin resistance independent of changes in body weight. It is likely that a similar sequence occurs in the transition from the prediabetic state to Type 2 diabetes in humans. More recently, other potential players in the etiology of the Metabolic Syndrome have been suggested including endothelial dysfunction and acetylation-stimulating protein (ASP). It has been suggested that endothelial dysfunction may be an antecedent for both Type 2 diabetes and the Metabolic Syndrome. In addition, ASP is a serious new candidate for an important role in insulin resistance. The ASP pathway plays a critical role in fatty acid metabolism and storage, and it has been suggested that ineffective storage of fatty acids by adipocytes due to a defect in the ASP pathway may lead to insulin resistance and Type 2 diabetes.
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PMID:Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. 1084 50

Metabolic syndrome, insulin resistance, prediabetes, and overt type 2 diabetes mellitus are associated with an accelerated atherosclerosis (atheroscleropathy). This quartet is also associated with multiple metabolic toxicities resulting in the production of reactive oxygen species. The redox stress associated with these reactive oxygen species contribute to the development, progression, and the final fate of the arterial vessel wall in prediabetic and diabetic atheroscleropathy. The prevention of morbidity and mortality of these intersecting metabolic diseases can be approached through comprehensive global risk reduction.
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PMID:Intimal redox stress: accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy. 1239

Type 2 diabetes mellitus is a chronic insidious process contributing to an overwhelming amount of morbidity and mortality, much of which is related to atherosclerosis, which often accompanies and complicates the natural history of diabetes. Although considerable attention has focused on new insights into diabetic mechanisms and emerging treatments, perhaps one of the greatest opportunities for decreasing the toll of diabetes and its late-stage complications may be intervening earlier in the disease process. Such notions redirect attention toward the concept of prediabetes mellitus as a potentially discrete syndrome, which may be identifiable in clinical practice. This article seeks to offer support for this hypothesis by considering the data surrounding prediabetes mellitus, with particular attention on the mechanistic and clinical links to atherosclerosis.
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PMID:Prediabetes mellitus and its links to atherosclerosis. 1264 41

Type 2 diabetes is associated with a marked increase in the incidence of coronary artery disease (CAD); however, the correlation between glycemia and CAD in patients with type 2 diabetes is only modestly positive. This relatively weak association between glycemia and CAD in subjects with diabetes may be caused by the existence of an atherogenic prediabetic state. In the San Antonio Heart Study, subjects who start with normal glucose tolerance and later develop type 2 diabetes have increased triglyceride levels, increased systolic blood pressure, and decreased levels of high-density lipoprotein cholesterol before the onset of type 2 diabetes. The basis for these atherogenic prediabetic changes may be related to insulin resistance rather than reduced insulin secretion. Recently, interest has focused on a possible role of fibrinolysis and increased subclinical inflammation, as determined by high-sensitivity C-reactive protein (CRP) levels. The Insulin Resistance Atherosclerosis Study found that insulin resistance, as determined by a frequently sampled glucose tolerance test, is significantly related to higher CRP levels, higher fibrinogen, and higher plasminogen activator inhibitor-1 (PAI-1) levels. The investigators also have shown that high PAI-1 and CRP levels are predictors of the development of type 2 diabetes. In addition, the Women's Health Study has shown that high CRP levels predict type 2 diabetes. Insulin-sensitizing interventions have been demonstrated to reduce these nontraditional risk factors. Rosiglitazone, an agent with insulin-sensitizing properties, decreases PAI-1 and CRP levels. Some of the adverse cardiovascular effects seen in patients with type 2 diabetes may be reversed by insulin-sensitizing agents.
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PMID:Insulin resistance, inflammation, and the prediabetic state. 1295 23

Numerous authors suggested postprandial blood glucose elevation as a significant contributor in development of macroangiopathy. Epidemiological studies and animal experiments delivered supportive data about causal relationship between postprandial hyperglycaemia and macroangiopathy in type 2 diabetes. Interestingly there is no chronological correlation between presence of hyperglycaemia and development of macroangiopathy neither in type 2, nor in type 1 diabetics. Strict metabolic control does not result in slowing progression of macroangiopathy (glucose paradox). Premature macroangiopathy documented in the prediabetes phase of type 2 diabetes is strongly related to presence of insulin resistance, hyperinsulinaemia, high blood pressure, and dyslipidaemia; development of atherosclerosis in advanced stage of type 1 diabetes is also rather associated with presence of high blood pressure and dyslipidaemia but not that of hyperglycaemia. With regard to role of postprandial hyperglycaemia it should be emphasized, that not the postprandial blood glucose elevation per se, but rather the postprandial complex metabolic cluster (hyperinsulinaemia, hypertrygliceriadaemia, etc) is supposed to be related with development of macroangiopathy in patients with metabolic syndrome and type 2 diabetes.
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PMID:[Clinical significance of blood glucose levels in the pathogenesis of (atherosclerotic) macroangiopathy]. 1515 91

Diabetes mellitus and the metabolic syndrome (MS) are reaching epidemic proportions in the United States, and cardiovascular disease continues to be the leading cause of death among patients with diabetes. A range of noninvasive screening tools may help reduce the morbidity and mortality of patients with diabetes because of early detection of subclinical cardiovascular disease and active monitoring of the effectiveness of therapy. Surrogate markers of subclinical disease include conventional and contrast-enhanced ultrasound imaging of carotid artery intima-media thickness (c-IMT), 2-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance imaging, ankle-brachial indices, and brachial artery reactivity testing. Because these noninvasive imaging tools are relatively comfortable and entail relatively low risk to the patient, they are ideal for initial screening and for the repeated imaging that is required for monitoring the effectiveness of therapy. Moreover, when used in large numbers of patients with diabetes, prediabetes, and the MS, these imaging tools may be useful in developing and validating thresholds for the use of lipid-lowering therapy as well as clear therapeutic goals for this population. In addition, contrast-enhanced c-IMT scans now produce real-time images of the vasa vasorum and neovascularization of atherosclerotic plaque, potentially causing a paradigm shift in our view of the genesis of atherosclerosis and affecting treatment options for all populations. Thus, surrogate markers may not only help improve individual patient outcomes, they also may help direct scarce medical resources to maximize medical benefits, improve overall medical care, and minimize costs and untoward side effects.
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PMID:Role of surrogate markers in assessing patients with diabetes mellitus and the metabolic syndrome and in evaluating lipid-lowering therapy. 1517 15

Clinically recognized disorders of glucose metabolism include impaired fasting glucose, impaired glucose tolerance (both termed prediabetes), and diabetes mellitus. Type 2 diabetes mellitus affects 6% to 13% of adults in the United States. Among patients with recent stroke, 70% will have known diabetes, occult diabetes (detectable on an oral glucose tolerance test), or prediabetes. Type 2 diabetes mellitus is associated with a two- to six-fold increased risk for first or recurrent ischemic stroke. The mechanisms for the association are myriad and include the effects of hyperglycemia on vascular tissues and coagulation, and aberrations in blood pressure regulation, lipid metabolism, endothelial function, vascular inflammation, lipid metabolism, smooth muscle cell proliferation, and fibrinolysis. The most effective strategies to prevent stroke among people with diabetes include blood pressure control, antiplatelet therapy, and statin therapy. Tight glycemic control is recommended to prevent microvascular disease, but the effect on macrovascular disease, including stroke, has not been proven. Target blood pressure should be less than 130/80. Antiplatelet therapy may be accomplished with 81 to 325 mg of aspirin daily or 75 mg of clopidogrel daily. Statins should be given in dosages effective to reduce low-density lipoprotein cholesterol to less than 100 mg/dL. For glycemic control, first line therapy for most patients is metformin, starting at 500 mg daily. With time, most patients will need two or three oral medications from different classes and many eventually will require insulin therapy. Prevention of diabetes may be best accomplished by identifying those at risk and modifying diet, weight, and exercise habits. Screening for prediabetes and diabetes is appropriate for men and women older than 45 years and all individuals with vascular disease. Insulin resistance and impaired insulin secretion is the major underlying defect in type 2 diabetes mellitus. It also affects 50% of nondiabetic subjects with a recent ischemic stroke. Emerging evidence has linked insulin resistance to the pathophysiologic derangements in type 2 diabetes mellitus that accelerate atherosclerosis. Treatment of insulin resistance with weight loss, exercise, or medication can correct these derangements, and represents a promising approach to stroke prevention.
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PMID:Type 2 Diabetes Mellitus and Insulin Resistance: Stroke Prevention and Management. 1546 22

Diabetes mellitus is, so called, the disease of the blood vessel. Indeed in many cases, atherosclerosis is already developed from the prediabetic state because of an existence of insulin resistance. Therefore, it is very important to elucidate the pathophysiological relationship between diabetes and cerebrovascular disease accompanied with intravascular calcium precipitation. Here we introduce the recent topics about the underlying relation between diabetes and cerebrovascular disease with atherosclerotic disorders.
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PMID:[Diabetes mellitus and the cerebrovascular disease]. 1577 95


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