Diabetes vascular complications

Yamagishi S, Imaizumi T. Diabetic vascular complications pathophysiology, biochemical basis and potential therapeutic strategy. Curr Pharm Des. 2005 11 2279-2299. 

There are a number of complications that arise as the result of poorly treated or unstabilized diabetes. Vascular Complications... 

Inoguchi, T., and H. Nawata. 2005. NAD(P)H oxidase activation a potential target mechanism for diabetic vascular complications, progressive beta-cell dysfunction and metabolic syndrome. Curr. Drug Targets. 6 495-501. 

Szabo, C., J.G. Mabley, S.M. Moeller, R. Shimanovich, P. Pacher, L. Viiag et al. (2002). Pathogenic role of peroxynitrite in the development of diabetes and diabetic vascular complications Studies with FP15, a novel, potent peroxynitrite decomposition catalyst. Mol Med. 8, 571-580. 

Giugliano, D., Ceriello, A., and Paolisso, G., Oxidative stress and diabetic vascular complications. Diabetes Care, 19, 257-267, 1996. 

PARK, J. Y, HA, S. W. KING, G. L. 1999. The role of protein kinase C activation in the pathogenesis of diabetic vascular complications. Peril Dial Int, 19 Suppl 2, S222-7. 

Of the various compounds that inhibit or correct individual steps in the pathophysiological sequence leading to vascular complications of diabetes, two stand out pyridoxamine and benfotiamine (Figure 10.1). Pyridoxamine is a member of the vitamin Bg vitamer group. Benfotiamine is a lipid-soluble vitamin Bj analogue. Their use as therapeutic agents in the treatment of diabetic vascular complications has much potential in view of their lack of toxicity. 

Way, KJ, Katai, N and King, GL (2001) Protein kinase C and the development of diabetic vascular complications. Diabetic Medicine, 18, 945-959. 

Diabetes continues to be a major cause of excessive morbidity, severe disability and premature death in Western populations. In developed countries, the cost of diabetes to society may be estimated to be as high as 5% of the total health costs, much of which relates to the chronic vascular complications of this disorder (Williams, 1991). The vascular lesion in diabetes consists of (1) microangiopathy, distinguished by thickening of capillary basement membranes resulting in increased vascular permeability, which is clinically manifested as diabetic retinopathy (Fig. 12.1a) and/or nephropathy (Fig. 12.1b), and (2) macroangiopathy (Fig. 12.2),... 

Sinclair A.J. (1993). Free radical mechanisms and vascular complications of diabetes mellitus. Diabet. Rev. 2, 7-10. 

Rhetsinine (2), isolated from the hot water extract of Evodia rutae-carpa (family Rutaceae), was found to inhibit aldose reductase with an IC50 value of 24.1 /rM furthermore, the isolate inhibited sorbitol accumulation by 79.3% at 100 This compound could find potential use in the treatment of diabetic complications. Tetramethylpyrazine (3), one of the active components in Qing Huo Yi Hao, displayed strong antioxidant and endothelial protective effects, which can be comparable as Qing Huo Yi Hao this result indicated that some therapeutic potential of Qing Huo Yi Hao for vascular complications of diabetes may be attributed to the presence of tetramethylpyrazine (3). ... 

It is indicated in non-insulin dependent diabetes mellitus, diabetes with or without obesity in adults, diabetes in the elderly and diabetes with vascular complications. 

Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus the role of endothelial dysfunction. Clin Sci. 2005 109 143-159. 

The National Glycohemoglobin Standardization Program (NGSP) used the CRMLN model to establish a reference laboratory network to standardize glycated hemoglobin (i.e., HbAlc) [33, 34], The purpose of the NGSP is to standardize HbAlc so that clinical laboratory results are comparable to the Diabetes Control and Complications Trial (DCCT) where relationships were established to mean blood glucose and risk for vascular complications. 

Fadini GR Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005 45 1449-1457. 

Role of Hyperglycemia and Redox-Induced Signaling in Vascular Complications of Diabetes... 

Fig. 9.1 Schematic model depicting the key events which mediate diabetes-associated vascular complications. Diabetes/hyperglycemia augments the levels of vasoactive peptides including Ang II/ET-1 that enhance the generation of reactive oxygen species (ROS). ROS-induced activation of growth-promoting signaling pathways, such as PKC and MAPK, contributes to aberrant vascular functions.

Most diabetics are in this category. Genetic factors rather than viruses or autoimmune antibodies are apparently causal. The metabolic alterations observed are milder than those described for IDDM (for example, NIDDM patients typically are not ketotic), but the long-term clinical consequences can be just as devastating (for example, vascular complications and subsequent infection can lead to amputation of the lower limbs). 

When 16 diabetic and hypertensive postmenopausal women aged 47-57 years were treated cyclically with estradiol plus norgestrel, existing proteinuria and even creatinine clearance often improved (4). The effects were unrelated to conventional risk factors for vascular complications, such as raised blood pressure, plasma glucose, or serum cholesterol. 

In comparison to the n-6 series, much less attention has been paid to the involvement of n-3 fatty acids in diabetic neuropathy, although the beneficial effects offish-oil supplements, a rich source of these fatty acids, in the prevention of atherosclerosis and hypertension in animal models and patients with vascular complications is well known (Lands et al. 1992). Proposals for the mechanisms by which n-3 fatty acids act include serving as precursors of vasoactive prostanoids and acting as shmulants for production of relaxing factors, such as nitric oxide (Lands etal. 1992 Boulanger 1990 McVeigh etal. 1993). 

Pancreatic diabetes is usually a late manifestation that is commonly associated with pancreatic calcification. Ketoacidosis, vascular complications, and nephropathy are uncommon with this form of diabetes. 

Macrovascular Complications. Metformin reduced macro vascular complications in obese subjects in the UKPDS. " Metformin significantly reduced all-cause mortality and risk of stroke vs. intensive treatment with sulfonylureas or insulin. Metformin also reduced diabetes-related death and myocardial infarctions vs. the conventional treatment arm of the UKPDS. Metformin should be included in the therapy for all type 2 DM patients, if tolerated and not contraindicated, as it is the only oral antihyperglycemic medication proven to reduce the risk of total mortality and cardiovascular death. 

In 18 diabetic children (40 healthy controls) and 20 diabetic children with no proteinuria or evidence of retinal vascular complications on fundoscopy (10 healthy controls), the excretion of GBM antigens was examined by im-munoelectrophoresis using a rabbit antihuman GBM serum (L15, S15). Eleven of the 18 and 10 of the 20 diabetic children, respectively, exhibited a-1 mobility, while the remaining diabetics and all the healthy children presented with ot-2 mobility- On in vitro ineubation with glucose, GBM antigens of healthy children now possessed a-1 mobility. Examination of GBM, isolated from kidneys obtained at surgery or within a few hours of... 

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