Approaches to Prevention of Cardiovascular Complications and Events in Diabetes Mellitus

Abstract

Diabetes mellitus affects about 8% of the adult population. The estimated number of patients with diabetes, presently about 170 million people, is expected to increase by 50-70% within the next 25 years. Diabetes is an important component of the complex of 'common' cardiovascular risk factors, and is responsible for acceleration and worsening of atherothrombosis. Major cardiovascular events cause about 80% of the total mortality in diabetic patients. Diabetes also induces peculiar microangiopathic changes leading to diabetic nephropathy conducive to end-stage renal failure, and to diabetic retinopathy that may progress to vision loss and blindness. In terms of major cardiovascular events, coronary heart disease and ischaemic stroke are the main causes of morbidity and mortality in diabetic patients. Peripheral arterial disease frequently occurs, and is more likely to be conducive to critical limb ischaemia and amputation than in the absence of diabetes. Although there are a number of differences in the pathogenesis and clinical features of diabetic macroangiopathy and microangiopathy, these two entities often coexist and induce mutually worsening effects. Endothelial injury, dysfunction and damage are common starting points for both conditions. Causes of endothelial injury can be distinguished into those 'common' to nondiabetic atherothrombosis, such as hypertension, dyslipidaemia, smoking, hypercoagulability and platelet activation; and those more specific and in some cases 'unique' to diabetes and directly related to the metabolic derangement of the disease, such as (i) desulfation of glycosaminoglycans (GAGs) of the vascular matrix; (ii) formation of advanced glycation end-products (AGE) and their endothelial receptors (RAGE); (iii) oxidative and reductive stress; (iv) decline in nitric oxide production; (v) activation of the renin-angiotensin aldosterone system (RAAS); and (vi) endothelial inflammation caused by glucose, insulin, insulin precursors and AGE/RAGE. Prevention of major cardiovascular events with the antithrombotic agent aspirin (acetylsalicylic acid) is widely recommended, but reportedly underutilised in patients with diabetes. However, some data suggest that aspirin may be less effective than expected in preventing cardiovascular events and especially mortality in patients with diabetes, as well as in slowing progression of retinopathy. In contrast, a recent study found picotamide, a direct thromboxane inhibitor, to be superior to aspirin in diabetic patients. Clopidogrel was either equivalent or less active in diabetic versus nondiabetic patients, depending upon different clinical settings.Recent studies have shown that some GAG compounds are able to reduce micro- and macroalbuminuria in diabetic nephropathy, and hard exudates in diabetic retinopathy, but it is as yet unknown whether these agents also influence the natural history of microvascular complications of diabetes. Lifestyle changes and physical exercise are also essential in preventing cardiovascular events in diabetic patients. Avail...

Short Term Effects of Atorvastatin on Endothelial Functions and Oxidized LDL Levels in Patients with Type 2 Diabetes

“…Endothelial dysfunction is shown in both type 1 and type 2 diabetic patients [3]. In diabetes, hyperglycemia activates protein kinase C and thus cause increased secretion of vasoconstrictor prostaglandins.…”

Type 1 Diabetes Mellitus: Redefining the Future of Cardiovascular Complications with Novel Treatments

“…Microvascular complications include nephropathy, retinopathy and neuropathy (Coccheri, 2007;Fowler, 2008;. There is a direct clinical practice to link these complications with DM type 1 rather than type 2 (Retenakaran and Zinman, 2008).…”

“…These cardiovascular complications are mostly focused in clinical practice to type 2 DM (Fowler, 2008), and increased in rate as well in type 1 DM (Mcphee et al, 2008); however, the mortality impact of cardiovascular diseases in both DM types 1 and 2 is similar (Juutilainen et al, 2008) contributing to 80 % of the mortality and morbidity (Coccheri, 2007). More alarmingly, development of macrovascular complication might not manifest in type 1 DM until 10 years proceeding diagnosis (King et al, 2005).…”

“…This is implied from data linking high levels of Ang II to DM and vasoconstriction (causing hypertension) , in addition to glomerular damaging ending up with nephropathy (Coccheri, 2007). Other than its direct effect as a potent vasoconstrictor, it was denoted to alter Endothelin-1 (ET-1) production , remodel cardiovascular structure (Parmar and Jadav, 2007), modulate heart and vessels (Nuwayri-salti et al, 2007), augment transforming growth factor-beta (TGF-) and boost proliferative and inflammatory events .…”

“…Other than its direct effect as a potent vasoconstrictor, it was denoted to alter Endothelin-1 (ET-1) production , remodel cardiovascular structure (Parmar and Jadav, 2007), modulate heart and vessels (Nuwayri-salti et al, 2007), augment transforming growth factor-beta (TGF-) and boost proliferative and inflammatory events . In conjunction; modulation of insulin significance is obtained , either by directly halting signaling mechanism of insulin per se or damaging structure and function of -cells via local pancreatic RAS (Coccheri, 2007). Angiotensin II has 2 receptors: Ang II Type 1 receptor (AT1R) and Ang II Type 2 receptor (AT2R).…”