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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The small and large vessel disease associated with diabetes mellitus is responsible for its morbidity and mortality. Although much of the pathogenesis remains to be clarified, the role of hyperinsulinemia and hyperglycemia per se in the progression of vascular disease is beginning to emerge. Hyperinsulinemia increases the release of very low density lipoprotein (VLDL) and may also be responsible for the low HDL cholesterol levels in patients with diabetes. Hyperinsulinemia also contributes to increased blood pressure, which independently promotes vascular disease. High glucose concentrations have direct influence on intracellular signal transduction, including effects on sorbitol pathway and associated changes of pyridine nucleotides, the de novo synthesis of diacylglycerol with subsequent stimulation of protein kinase C, and possibly changes in the cellular generation of myoinositol. Hyperglycemia also exerts long-lasting changes in cellular function, which result from non-enzymatic glycosylation of matrix and membrane proteins with subsequent binding of these proteins to specific receptors. These receptors are termed the advanced glycosylation end-products (AGE) receptors. Their activation leads to an increased release of cytokines and growth factors including PDGF, interleukins, TNF-alpha, and TGF-beta, all of which may act concomitantly in the disease process.
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PMID:The role of hyperglycemia and hyperinsulinemia in the pathogenesis of diabetic angiopathy. 890 9

The major risk factors appear to explain only a small proportion of the excess risk of coronary heart disease in patients with Non-Insulin-Dependent Diabetes Mellitus (NIDDM). Among novel risk markers that have been-proposed to explain the susceptibility of NIDDM subjects to coronary heart disease are insulin resistance, elevated concentrations of proinsulin-line molecules, plasminogen activator inhibitor, and microalbuminuria. Several prospective studies have shown that hyperinsulinemia predicts coronary heart disease, perhaps independently of established risk factors. Some of this excess risk may be through the dyslipidemia, or the elevation in activity of plasminogen activator inhibitor, an inhibitor of fibrinolysis, which relate to hyperinsulinemia. However proinsulin-like molecules show similar relationships with both risk factors and with prevalent coronary heart disease as does insulin, despite low concentrations of these molecules in the circulation, suggesting a causative relationship is improbable. Furthermore, the link between insulin resistance and microalbuminuria, a powerful predictor of vascular disease in its own right, is poorly understood through known mechanisms. This clustering leads to the possibility of a link with coronary heart disease through other mechanisms. It is proposed that the pathogenesis of this link is endothelial dysfunction, which may predicate both impaired insulin action, through effects of blood flow and insulin transport, and the associated dyslipidemia, impaired fibrinolysis, microalbuminuria, and atherogenesis. In terms of etiology, the links of all these risk factors with evidence of growth retardation in early life may suggest a role of the thirfty phenotype hypothesis-impaired organogenesis resulting from poor maternal nutrition during pregnancy.
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PMID:The Deidesheimer meeting: significance of classical and new risk factors in non-insulin-dependent diabetes mellitus. 910 95

AIM OF ANTIHYPERTENSIVE TREATMENT IN DIABETICS: Prevention or treatment of hypertensive in diabetic patients reduces the incidence and progression of diabetic complications of retinopathy and nephropathy, cerebro- and cardio-vascular disease, and widespread macroangiopathy. Therefore, in patients with diabetes and hypertension beside good glucose control, the basic and probably major intervention steps is to normalize blood pressure. Antihypertensive treatment usually means life-long use of antihypertensive drugs. METABOLIC EFFECTS OF DIFFERENT DRUG CLASSES: Given the known diabetogenic properties of several antihypertensive drugs and their high rate of use, in probably a substantial proportion of patients with diabetes or prone to develop diabetes, treating arterial hypertension with conventional diuretics and/or beta-blockers might, in the long term, offset the beneficial effects of lowering blood pressure. Furthermore, there are conflicting reports of increased mortality in patients treated with diuretics, beta-blockers or calcium antagonists. Consequently, metabolic aspects and side effects of antihypertensive drugs are key elements in determining the preference for a specific antihypertensive regimen. Although the impact of hyperinsulinemia/insulin resistance on morbidity and mortality is an open question, it is preferable that antihypertensive treatment does not increase insulin resistance and/or hyperinsulinemia. Chronic beta-blocker treatment can be accompanied by an increase in insulin resistance. Calcium antagonists and angiotensin converting enzyme (ACE) inhibitors and alpha(1)-blockers are neutral or might even improve insulin resistance and lipid profile. Thiazides impair glucose tolerance, increase low-density lipoprotein cholesterol and decrease potassium, although these side effects are dose-dependent. Unless diuretics are needed for reasons other than hypertension, treatment of diabetics with thiazides should be avoided until the influence of these agents on prognosis is clarified. If the addition of a diuretic is needed, the metabolically neutral indapamide would seem a reasonable choice. PREFERRED FIRST-LINE TREATMENT: On the basis of favorable pharmacological profiles, ACE inhibitors and certain calcium antagonists have emerged as the preferred first-line drugs in the treatment of the hypertensive diabetic patient. In diabetics with nephropathy, therapy is usually initiated with an ACE inhibitor. Moreover, the combination of an ACE inhibitor and a calcium antagonist that lowers the heart rate (such as verapamil) might offer even greater advantages than either class of drug alone, since they combine metabolic neutrality with added antihypertensive and renal protective efficacy.
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PMID:Requirements for antihypertensive therapy in diabetic patients: metabolic aspects. 921 2

Accelerated coronary artery disease is the most serious obstacle to long-term survival in heart transplant recipients. Hyperlipemia, hyperinsulinism, and changes in endothelial cell hemostatic function have been implicated in cardiac allograft vascular disease. Both lovastatin and bezafibrate are safe, effective, and well tolerated therapies for hyperlipidemia. Our study compares the effect of these lipid-lowering drugs in 21 patients with post-heart transplantation hyperlipidemia on different risk factors related to insulin resistance syndrome. Patients were given the same diet for 3 months, then randomized to lovastatin or bezafibrate for a period of 8 weeks, and crossed over to an additional 8 weeks of either bezafibrate or lovastatin. Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment. Transplant patients had higher insulin (35 +/- 3 vs 24 +/- 3 microIU/L), fibrinogen (298 +/- 15 vs 261 +/- 14 mg/dl), and plasminogen activator inhibitor-1 (PAI-1) (17 +/- 2 vs 11.7 +/- 2 arbitrary units/ml) plasma levels than controls. Significant decreases in insulin (-37 +/- 3%), fibrinogen (-12 +/- 4%), and PAI-1 plasma levels (-18 +/- 12%) were only observed after bezafibrate treatment. In conclusion, bezafibrate decreases plasma insulin, fibrinogen, and PAI-1 in hyperlipidemic heart transplant recipients.
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PMID:Comparison of bezafibrate versus lovastatin for lowering plasma insulin, fibrinogen, and plasminogen activator inhibitor-1 concentrations in hyperlipemic heart transplant patients. 938 94

An association between hyperhomocysteinemia and premature atherosclerosis in patients with non-insulin-dependent diabetes mellitus (NIDDM) has recently been described. Little is known about the role of insulin in homocysteine [H(e)] metabolism. We measured plasma H(e) concentrations in the fasting state and during a hyperinsulinemic-euglycemic clamp in normal subjects and patients with NIDDM. Plasma H(e) decreased significantly from 7.2 +/- 2.6 to 6.0 +/- 2.7 mmol/L (P < .01) in normal subjects, but did not change in patients with NIDDM (6.0 +/- 2.7 to 5.9 +/- 2.5 mmol/L, respectively). These data suggest that plasma H(e) concentrations are regulated by acute hyperinsulinemia in normal subjects, but not in insulin-resistant NIDDM subjects. These abnormalities may have implications for the pathogenesis of premature vascular disease associated with NIDDM.
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PMID:Plasma homocysteine concentrations are regulated by acute hyperinsulinemia in nondiabetic but not type 2 diabetic subjects. 962 67

Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogen properties. Increased circulating ET-1 levels were found in patients with atherosclerosis as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM) suggesting a role in the pathogenesis of these disorders. The aim of the present study was to ascertain the influence of the NIDDM on plasma ET-1 levels in patients with advanced atherosclerotic lesions. The circulating ET-1 levels were measured in 16 NIDDM patients (68.4 +/- 8.4 years) with macroangiopathy and in ten patients (65.3 +/- 11 years) with atherosclerosis without NIDDM. Twenty-two healthy subjects (43.1 +/- 18.3 years) served as controls. Circulating ET-1 levels were higher in NIDDM patients (6.8 +/- 2.8 pg/mL) than both controls (3.1 +/- 1 pg/mL; p < 0.001) and patients with vascular disease but without NIDDM (4.7 +/- 1.6 pg/mL; p < 0.04). No significant relationship was found between age and ET-1 concentrations, and no differences were noted between men and women in the control group. This study demonstrated that circulating ET-1 levels are increased in patients with atherosclerosis and that those with NIDDM showed the highest ET-1 levels. These observations strongly support a role for ET-1 in the pathogenesis of atherosclerosis and also suggest that this peptide may be involved in the development of atherosclerotic lesions in the NIDDM. We speculated that chronic exposure to hyperinsulinemia and hypertriglyceridemia in the diabetic patients could account for the increased ET-1 levels found in these patients.
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PMID:Influence of non-insulin-dependent diabetes mellitus on plasma endothelin-1 levels in patients with advanced atherosclerosis. 964 35

Diabetes mellitus and particularly non-insulin-dependent diabetes mellitus (NIDDM) increases the risk for all manifestations of: (a) atherosclerotic vascular disease; (b) coronary heart disease (CHD); (c) cerebrovascular disease; and (d) peripheral vascular disease. NIDDM is known to be associated with several adverse cardiovascular risk factors, including: (i) hypertension; (ii) obesity; (iii) central obesity; (iv) hyperinsulinemia; and (v) serum lipid and lipoprotein abnormalities, characterized mainly by elevated serum total triglycerides and low high-density lipoprotein cholesterol. This review will discuss the prevalence of hypertension in NIDDM, the role of hypertension to increase the risk for macrovascular complications in NIDDM and finally trial evidence for the beneficial effect of blood pressure lowering in patients with NIDDM.
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PMID:Hypertension and macrovascular disease--the killing fields of NIDDM. 964 57

Diabetes mellitus is a strong risk factor for all manifestations of atherosclerotic vascular disease, coronary heart disease (CHD), cerebrovascular disease and peripheral vascular disease. Diabetes can be classified into two main subtypes, insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus (NIDDM). This review focuses only on NIDDM. Also, in impaired glucose tolerance (IGT), a precursor stage of diabetes, the risk of macrovascular disease is substantially increased. NIDDM and IGT are known to be associated with several adverse cardiovascular risk factors, including hypertension, obesity, central obesity, hyperinsulinemia and serum lipid and lipoprotein abnormalities, characterized mainly by elevated serum total triglycerides and low high-density lipoprotein cholesterol. Practically no information is available on the role of different cardiovascular risk factors to predict macrovascular complications in subjects with IGT. The role of different cardiovascular risk factors with respect to the risk of CHD, stroke and peripheral vascular disease will be discussed.
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PMID:Epidemiology of risk factors for cardiovascular disease in diabetes and impaired glucose tolerance. 969 44

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.
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PMID:Pathogenesis of atherosclerosis in diabetes and hypertension. 1005 43

Patients with diabetes have an increased prevalence of premature atherosclerotic vascular disease, and alterations in plasma coagulation proteins have been incriminated as a possible cause. The roles of hyperglycemia and hyperinsulinemia in the pathogenesis of these changes are unknown. To examine the effects of prolonged hyperglycemia and of selective hyperinsulinemia on the tissue factor pathway of blood coagulation, nine healthy young men were infused with glucose to maintain levels at 11.1 mmol/l (approximately 200 mg/dl) for 18-72 h (hyperglycemia-hyperinsulinemia group). Five normal men were infused with regular insulin to maintain levels comparable to that in the previous group (900 pmol/l, approximately 150 microU/ml) and with glucose to maintain levels at 5.6 mmol/l (approximately 100 mg/dl) (euglycemia-hyperinsulinemia group). Measured were plasma activated factor VII activity (FVIIa), FVII coagulant (FVIIC) activity, FVIII coagulant (FVIIIC) activity, tissue factor pathway inhibitor (TFPI) antigen, and thrombin markers; and serum glucose, insulin, and electrolytes. Plasma FVIIa, FVIIC, FVIIIC, and TFPI rose during hyperglycemic-hyperinsulinemia but not during euglycemic-hyperinsulinemia. Markers of thrombin generation rose transiently and inconsistently during hyperglycemia-hyperinsulinemia. We concluded that in normal subjects, hyperglycemia-hyperinsulinemia induced activation of the tissue factor pathway, reflected by increases in plasma FVIIa, FVIIC, and TFPI. This activation was independent of hyperinsulinemia, hypertriglyceridemia, and hyperosmolality. The elevations in plasma coagulation factors during hyperglycemia-hyperinsulinemia, characteristic of type 2 diabetes, may constitute a potential for enhanced thrombin generation and thrombosis when triggered by exposure of tissue factor, such as during arterial plaque rupture.
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PMID:Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men. 1033 23


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