Vascular disease, in diabetes mellitus

Janka HU, Standi E, Mehnert H. Peripheral vascular disease in diabetes mellitus and its relation to cardiovascular risk factors screening with Doppler ultrasonic technique. Diabetes Care 1980 3 207-213. 

The incidence of type 2 (noninsulin-dependent) diabetes mellitus continues to increase in the United States (1). Consequently, the associated morbid and mortal events from the associated microvascular and macrovascular complications of this disease have also risen (1). The preponderance of research toward the understanding of vascular disease in diabetes has been directed toward the delineation of end organ injury from microvascular disease. Consequently, the focus on macrovascular peripheral vascular disease has been relatively ignored. However, several studies have elucidated both the incidence and prevalence of peripheral vascular disease associated with both type 1 (insulin-dependent) and type 2 diabetes mellitus. In general, these studies have found that the duration of diabetes is perhaps the best correlate to predict the development of coronary artery and renal disease, as well as other associated end organ injuries that have not consistently correlated with the development of peripheral vascular disease. 

There are discordant results between the effects of vitamin E supplements in observational studies, in which they seem to reduce the risk of cardiovascular disease, and the results of interventional studies, in which they seem to have the opposite effect. In an extensive review of the benefits and adverse effects of vitamin E, the authors, employees of IdeaSphere Inc., which markets vitamins and nutrients, concluded that healthy consumers should not change their current use of vitamin E supplements since most of the studies included in the three recent neutral to unfavorable meta-analyses were not conducted on free-living healthy individuals. .. [and] only four of 28 studies included in these meta-analyses involved healthy individuals [45 ]. They urged that the guidelines set forth by the Institute of Medicine [in 2000] should still be embraced and that healthy individuals should not use more than 1000 mg of vitamin E daily . They concurred with the findings of the HOPE study, a randomized, placebo-controlled study of the use of vitamin E 400 lU/day over 7 years [46 ], that vitamin E did not prevent cancer or major cardiovascular disease events in subjects with pre-existing vascular disease or diabetes mellitus, and may have increased the risk of heart failure, and that, as the authors of the HOPE study concluded, such individuals should be warned to beware of natural products . 

There is a major difference between the role of free radicals in cancer and other pathologies such as cardiovascular diseases, hypertension, diabetes mellitus, etc. In contrast to the latter diseases where the sources of free radical overproduction are well established (vascular cells and macrophages in cardiovascular diseases and leukocytes in inflammation), the origin and the levels of free radical production in tumor cells are still uncertain. 

The neuromuscular complications of diabetes mellitus are most often neuropathic in origin, with distal sensorimotor polyneuropathies being the most common. In addition, ischemic infarction of skeletal muscle may occur due to occlusive vascular disease, with small and medium-sized arterioles particularly affected. This occurs in poorly-controlled diabetes and affects thigh, muscles in most cases. In acute stages, muscle biopsy findings are those of widespread muscle necrosis, edema, and phagocytic cell infiltration. Muscle regeneration may be incomplete and increased fibrous connective tissue may replace lost muscle tissue. 

Wong BW, Wong D, McManus BM. Characterization of fractalkine (CX3CL1) and CX3CR1 in human coronary arteries with native atherosclerosis, diabetes mellitus, and transplant vascular disease. Cardiovasc Pathol 2002 ll(6) 332-338. 

The inactivation of enzymes containing the zinc-thiolate moieties by peroxynitrite may initiate an important pathophysiological process. In 1995, Crow et al. [129] showed that peroxynitrite disrupts the zinc-thiolate center of yeast alcohol dehydrogenase with the rate constant of 3.9 + 1.3 x 1051 mol-1 s-1, yielding the zinc release and enzyme inactivation. Later on, it has been shown [130] that only one zinc atom from the two present in the alcohol dehydrogenase monomer is released in the reaction with peroxynitrite. Recently, Zou et al. [131] reported the same reaction of peroxynitrite with endothelial NO synthase, which is accompanied by the zinc release from the zinc-thiolate cluster and probably the formation of disulfide bonds between enzyme monomers. The destruction of zinc-thiolate cluster resulted in a decrease in NO synthesis and an increase in superoxide production. It has been proposed that such a process might be the mechanism of vascular disease development, which is enhanced by diabetes mellitus. 

Older patients have predominantly Type 2 diabetes mellitus, which shares with Type 1 the risk for retinopathy, nephropathy and neuropathy, but carries a greater risk for macrovascular complications such as coronary artery disease, stroke and peripheral vascular disease. Many such patients have associated obesity, hypertension and hyperlipidemia, compounding the risk of cardiovascular disease. The goals of treatment of DM in the elderly are to decrease symptoms related to hyperglycaemia and to prevent long-term complications. Treatment of type 2 DM can improve prognosis. In the UKPDS trial, sulphonylureas, insulin, and metformin were all associated with a reduction in diabetes-related... 

Diabetes mellitus is a disease related to carbohydrate metabolism in which insulin is absent, low in quantity, or a combination of both. It is characterized by hyperglycemia. Progress of the disease causes tissue or vascular damage, leading to diabetic complications such as retinopathy, neuropathy, cardiovascular disease, and foot ulcerations. 

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