With Diabetes

In addition to beneficial effects on lipids, HRT has also been shown to improve other risk factors for atherothrombosis in diabetic women. CRP, a cardiovascular risk marker, is known to be increased in patients with type 2 diabetes. Sattar and associates (159) in a 6-month, double-blind, placebo-controlled study reported that transdermal estradiol in conjunction with continuous oral norethisterone significantly reduced CRP concentrations in postmenopausal women with type 2 diabetes. This is in...

Effects of the Renin Angiotensin System on Insulin Signaling

The effects of RAS inhibition on insulin action have been attributed to changes in both the inhibition of Ang II ATI receptor signaling and enhancement of bradykinin B2 receptor action. ACE, also called kininase II, degrades bradykinin 1-9 and thereby reduces bradykinin B2 receptor activation (Fig. 2). Several reports have shown that bradykinin B2-receptor antagonism blocks the decreases in insulin resistance and enhanced glucose uptake associated with ACE inhibition (148,149,157) and is...

Quantitativequalitative abnormalities of lipoproteins

In poorly controlled diabetic patients, plasma LDL, intermediate density lipoproteins and very low-density lipoprotein (VLDL) levels are elevated (106-110). The increase in VLDL levels has been attributed to increased hepatic production or decreased clearance of VLDL (111) and may be very significant in the development of arteriosclerosis in diabetes and in women (112). HDL levels in diabetes vary with the type of diabetes and, in some groups, with glycemic control. In type 2 diabetic patients,...

Inhibitors of AGE Production

The production of AGE, as a result of prolonged exposure of proteins to chronic hyperglycemia, can result in direct quenching of NO and increasing the oxidative stress. Fig. 6. Forearm blood flow (FBF) dose-response curves to intra-arterial methacholine chloride infusion before and during coinfusion of vitamin C in noninsulin-dependent diabetic subjects. The concomitant infusion of methacholine and vitamin C resulted in an improved endothelium-depen-dent vasodilation compared with methacholine...

Effect of Insulin Resistance Treatment on Polycystic Ovary Syndrome Weight Loss

Weight reduction is of paramount importance and cornerstone of every therapeutic strategy in PCOS. Although obesity does not seem to be the primary insult in PCOS, many studies have demonstrated the beneficial impact of weight reduction on the manifestations of the syndrome and especially insulin sensitivity, risk for diabetes and adverse cardiovascular risk profile (199). The effect of weight reduction by a hypocaloric low-fat diet on the metabolic and endocrine variables was studied in obese...

Therapeutic implications

Consideration of the derangements in platelet function, the coagulation system, and the fibrinolytic system and their contributions to exacerbation of macrovascular disease in type 2 diabetes gives rise to several therapeutic approaches. Empirical use of aspirin (160-325 mg per day in a single dose) seems appropriate in view of the high likelihood that covert CAD is present even in asymptomatic people with type 2 diabetes and the compelling evidence that prophylactic aspirin reduces the risk of...

Potential preventive and therapeutic options Oral Hypoglycemic Agents

The cornerstone of DM therapy is optimal glycemic control, because hyperglycemia is the basis of all the metabolic disturbances that occurs in the disease. As shown previously, both in vivo and in vitro elevated glucose levels have been shown to cause abnormal endothelium-dependent relaxation. Lower glucose levels also result in a decrease in insulin levels, which consequently may also improve endothelial function. Therefore, therapy should be directed toward lowering glucose levels and...

Activation of the Dagpkc Pathway

One major advance in the understanding of diabetic vascular disease is the unraveling of changes in signal transduction pathways in diabetic states. One of the best-characterized signaling changes is the activation of DAG-PKC pathway. Such activation appears to be related to elevation of DAG, a physiological activator of PKC. Increases in total DAG contents have been demonstrated in a variety of tissues associated with diabetic vascular complications, including retina (78), aorta, heart (79),...

Melpomeni Peppa md Jaime Uribarri md and Helen Vlassara md

Advanced Glycoxidation End-Products Advanced Glycoxidation End-Products Advanced Glycoxidation End-Products Advanced Glycoxidation End-Products Microangiopathy Advanced Glycoxidation End-Products and Diabetic Macroangiopathy Antiadvanced Glycoxidation End-Product Strategies Conclusions References The incidence of diabetes, especially type 2 diabetes, is increasing at an alarming rate assuming epidemic proportions (1). Worldwide, 124 million people had diabetes by 1997, although an estimated 221...

Animal Models

STZ-induced diabetes increases atherosclerotic plaque area by four- to fivefold in the aorta of apo-E deficient mice (72,84,85). Treatment of diabetic apo-E - - mice with the ACE inhibitor perindopril reduces lesion area, macrophage infiltration, and collagen content (85). A similar reduction in aortic plaque area was observed in STZ-induced diabetic apo-E-deficient mice treated with the ATI receptor antagonist Irbesartan (72). Both ACE and ATI receptor expression are increased in aortic...

The coagulation system and diabetes mellitus

Activation of the coagulation system leads to the generation of thrombin and thrombin-mediated formation of fibrin from fibrinogen. The generation of thrombin depends on activation of procoagulant factors. It is limited by antithrombotic factors and inhibitors. Fibrinopeptide A (FPA) is released when fibrinogen is cleaved by thrombin. FPA has a very short half-life in the circulation and is cleared promptly by the kidneys. Elevated concentrations in blood are indicative of thrombin activity in...

Mechanisms

The mechanisms by which diabetes abolishes the cardiovascular protective effects of female sex hormones in premenopausal women are not well understood. In fact, the loss of the natural sex advantage in women with diabetes is independent of other diabetes-associated conventional risk factors. After adjusting for differences in hypertension, dyslipidemia, and obesity, the cardiovascular risk still remains higher in diabetic women than in men or women without diabetes (8,107). This suggests that...

Oxidative and Nitrosative Stress in Diabetes Induced Vascular Dysfunction

Various neurohumoral mediators and mechanical forces acting on the innermost layer of blood vessels, the endothelium, are involved in the regulation of the vascular tone. The main pathway of vasoregulation involves the activation of the constitutive, endothelial isoform of NO synthase (eNOS) resulting in NO production (53). Endothelium-depen-dent vasodilatation is frequently used as a reproducible and accessible parameter to probe endothelial function in various pathophysiological conditions....

Mechanisms responsible for the overexpression of pai1 in diabetes

Increased expression of PAI-1 in diabetes is undoubtedly multifactorial. A direct effect of insulin on the expression of PAI-1 has been suggested by a positive correlation between the concentration of insulin and PAI-1 in vivo (93,94,96,100-103,106). Triglycerides and their constituents (fatty acids) appear to contribute to the overexpression of PAI-1 in view of the fact that both insulin and triglycerides independently increase expression of PAI-1 by human hepatoma cells in vitro...

Conclusions and Future Directions

There are several plausible explanations for the divergent findings from the clinical trials and the observational studies regarding the effect of HRT on CVD in postmeno-pausal women. Some discrepancies may be methodological in nature and others may have a biological basis related to the pleiotropic effects of estrogens and the characteristics of the study population. The later may be related to age, time since menopause, state of the arterial endothelium and stage of atherogenesis. Genetic...

Clinical

13 The Metabolic Syndrome and Vascular S. J. Creely, Aresh J. Anwar, and Sudhesh Kumar 14 Diabetes and Samy I. McFarlane, Amal F. Farag, David Gardner, 15 Diabetes and Asha Thomas-Geevarghese, Catherine Tuck, 16 Diabetic Lloyd Paul Aiello and Jerry Cavallerano 17 Diabetic 18 Diabetic 19 Microcirculation of the Diabetic C. Cardiovascular System Peripheral Vascular System 20 Epidemiology of Peripheral Vascular Stephanie G. Wheeler, Nicholas L. Smith, and Edward J. Boyko 21 Noninvasive Methods to...