Therapeutic Possibilities

The latest therapeutic possibilities are being separated into two groups: the symptomatic and pathogenetically oriented therapy. One of the most important components of etiology based treatment is the stabilization of glycemic control. Based on safety and efficay data alpha-lipoic and benfotiamine acid should be considered as primary choices among pathogenetically oriented treatments of diabetic neuropathy. Interesting data were published about the aldose reductase inhibitor ranirestat. The symptomatic effect of antiepileptic drugs in diabetic painful neuropathy (DPN) is originated from several probable pharmacological properties. Gabapentin and Pregabalin have the largest efficacy and the most low frequency of adverse reactions among these drugs. Antidepressants also introduced for symptomatic treatment in DPN. In the last months few studies were released about the benefits of duloxetine. Mostly the combination therapy will be constantly applied in the future for the planning and treatment of DPN, the best choice could be collaborate symptomatic treatment and pathogenetically oriented.

The global stretch of diabetes mellitus is a most important contributing factor to the prediction that cardiovascular disease will become the main reason of mortality worldwide by the year 2020. (Bell 2002) Patients with diabetes display a patently augmented incidence of adverse cardiovascular events and less favourable results f after coronary interventions or from myocardial infarction. Additionally to affiliate dyslipidemia and hypertension, escalating data insinuates that damaged glycemic homeostasis has an unequivocal influence on the propagation and formation of atherosclerotic plaque. This is expected to underscore the investigation that even in the deficiency of ischemic symptoms the incidence of diabetes bestows a potential risk of clinical events similar to that pragmatic in non-diabetic survivors of myocardial infarction. As a consequence, treatment and prevention of diabetes is a main component of strategies intended to decrease cardiovascular risk (Horowitz 1993)

Clarifying the issues that support cardiovascular disease in diabetes is essential for the development of new therapeutic advances. (World Health Organization 1999) The occurrence of hypertension, hyperglycemia, and dyslipidemia, in correlation with systemic oxidative stress and inflammation, accelerates the propagation and formation of atherosclerotic plaque.(Horowitz 1993) This instigates observations from necropsy and small clinical studies that diabetes is categorized by diffuse atherosclerosis, with a preference for participation of distal segments in reasonably small vessels. However, no systematic evaluation of the pattern of associated arterial wall remodelling and coronary atherosclerosis has been achieved in a huge cohort of diabetic patients by imaging of the entire thickness of the coronary artery wall. (Wild, Roglic, Green, Sicree, King 2004)

Intravascular ultrasound (IVUS) allows evaluation of the effect of clinical characteristics on variations in coronary atheroma volume. More in recent times, IVUS has been utilized to assess the influence of medical therapies on the history of plaque progression. The present investigation conducted on the progression and extent of associated arterial wall remodelling and atherosclerosis in a larger number of diabetic patients presented with coronary artery disease whom went through serial evaluation by IVUS (Deshpande, Harris-Hayes, Shootman 2008)

The incidence of a larger extensive disease substantiates throughout unequivocal observations of the vessel wall the discovering that diabetic patients have an hasten form of atherosclerotic disease. A quantity of pathophysiologic irregularities likely explains the increasing rapid evolution of disease. The existence of diabetes is supplemented by a greater occurrence of established atherosclerotic risk factors comprising low levels of HDL cholesterol, hypertension; hypertriglyceridemia; the presence of minute, obesity and dense LDL particles;. nevertheless, traditional risk factors alone represent only a segment of the excess disease burden. Hyperglycemia and the potential generation of advanced glycation end products also seem to play an important role (Wheeler, Singh, Boyko 2007)

More than 50% of the population who are suffering from diabetes suffer from Macrovascular complications and this account's to 50-60% of the mortality in this high-risk population. Hyperglycemia, Hypertension, Dyslipidemia all play a vital role in diabetes-associated atherosclerosis, but controversy surrounds this independent risk factors especially in concerns with specific contributions. (Deshpande, Harris-Hayes, Shootman 2008)

The Macrovascular complications of diabetes was highlighted in studies with the use of the inhibitor advanced glycation aminoguanidine (AG), these macrovascular complications were a result of the in vivo relevance of Millard reaction and the advanced glycation end products or (AGEs). Studies show some evidence that AGEs could in fact induct atherosclerosis, through the used exogenous administrations of AGEs to mimic diabetes serum concentrations. The certain expression of atherogenic adhesion molecules implicated in atherogenesis, shows the interactions of AGEs with the endothelial cells. Lipoxiadation end products or (ALEs) for vascular complications have been seen along with glycoxidation products, meaning that it is not only AGEs which is the composition of oxygen and sugar. (Bell 2002) The interaction between AGEs and lipids can be seen with the characteristic hyperlipidemia, hypertension and reduced ALEs from the formation of the AGE inhibitor Pyridoxamine, through the studies in experimental obese Zucker rats, as a model of insulin resistance. Looking at the links it is yet to be elucidated that ALEs plays a vital role in the disease process of dylipidemia and hyperglycemia . Associations to the plague area in a model of diabetes-associated atherosclerosis can be formed with the prevention aortic AGE accumulation using wither the inhibitor of AG, AGE formation, or the AGE cross-link breaker as per recent studies. Extracellular collagenous proteins and a reduced expression in terms of proclerotic growth factors can be shown through the biological effects of AGEs, possibly leading to ALEs present on skin collagen and alterations in AGEs. Reduced build-up of AGEs within aortas, and the little sign of RAGE occur in the context of diabetes-associated atherosclerosis.(Davis, Brophy, Williams, Taylor 2006)

Previously non diabetic patients have shown the AGE accumulation in aortic atheroma. Increased CML within skill collagen can be associated to increased aortic CML. Investigations show that AGEs are in fact increased in diabetic. Information can be gathered about AGEs from the analysis of skin collagen through the historical glycemic control, particularly