Disease relevance of Diabetes Complications

• Aldose reductase in glucose toxicity: a potential target for the prevention of diabetic complications [1].
• The delineation of the role of this repressosome complex in regulating tissue-specific expression of GHR in diabetes mellitus provides a molecular model for the role of GH in the genesis of certain microvascular complications of diabetes mellitus [2].
• The advanced glycation end-product (AGE) hypothesis proposes that accelerated chemical modification of proteins by glucose during hyperglycemia contributes to the pathogenesis of diabetic complications [3].
• There was no difference in sex, HbA1c, the prevalence of smokers, serum lipids, or serum electrolytes between groups N and R at baseline, whereas age, the prevalence of hypertension, serum creatinine, and diabetic complications were more pronounced in group R than in group N [4].
• MPO/H(2)O(2)/HOCL/chlorinating species may represent an important pathway in diabetes complications and a new mechanism in phagocyte- and systemic infection-induced exacerbation of diabetic vascular diseases [5].

Psychiatry related information on Diabetes Complications

• This study evaluated the effects of sildenafil on men with erectile dysfunction and Type II diabetes and compared the results with glycated haemoglobin concentrations and chronic diabetic complications [6].
• Psychosocial factors and complications of IDDM. The Pittsburgh Epidemiology of Diabetes Complications Study. VIII [7].
• Increased SSAO-mediated deamination may contribute to protein deposition, the formation of plaques, and inflammation, and thus may be involved in the pathophysiology of chronic vascular and neurological disorders, such as diabetic complications, atherosclerosis, and Alzheimer's disease [8].
• The relations between blood glucose control (HbA(1c)), smoking, and health-related diabetes locus of control beliefs were studied in a consecutive adult sample of 187 patients with Type 1 diabetes who were free of diabetes complications [9].

High impact information on Diabetes Complications

• Aldose reductase inhibitors firmly link defects in myo-inositol metabolism to activation of the polyol pathway in diabetes; the resulting "sorbitol-myo-inositol hypothesis" has been extended from its application to the lenses and peripheral nerves to most of the tissues involved with diabetic complications [10].
• Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications [10].
• If one can assume that the fluorescence results from a browning product of glucose, our data suggest that there is an overall correlation between the severity of diabetic complications and cumulative glycemia over many years [11].
• Blood sugar and diabetic complications [12].
• The ability of benfotiamine to inhibit three major pathways simultaneously might be clinically useful in preventing the development and progression of diabetic complications [13].

Chemical compound and disease context of Diabetes Complications

• Potentially, the development of newer drugs that selectively inhibit AR-mediated glucose metabolism and signaling, without affecting aldehyde detoxification, may be useful in preventing inflammation associated with the development of diabetic complications, particularly micro- and macrovascular diseases [14].
• Recent evidence suggests that common stress-activated signaling pathways such as nuclear factor-kappaB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases underlie the development of these late diabetic complications [15].
• The increase in the concentration of fructose 3-phosphate in the lens of diabetic rats suggests that it and its hydrolysis product, 3-deoxyglucosone, may be responsible in part for the development of some diabetic complications in the lens [16].
• Oxybutynin for diabetic complications [17].
• These results, taken together with a recent demonstration of increased serum 3-DG levels in diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term diabetic complications such as nephropathy and atherosclerosis [18].

Biological context of Diabetes Complications

• Age-associated increases in collagen cross-linking and accumulation of advanced glycosylation products are both accelerated by diabetes, suggesting that glucose-derived cross-link formation may contribute to the development of chronic diabetic complications as well as certain physical changes of aging [19].
• Binding sites of the redox-regulated transcription factors NF-kappa B and AP-1 are located in the promoter region of a large variety of genes that are directly involved in the pathogenesis of diseases, e.g., AIDS, cancer, atherosclerosis and diabetic complications [20].
• Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences [21].
• To study the relationship between the aldose reductase gene and diabetic complications, an (A-C)n dinucleotide repeat sequence 2.1 kb upstream of the transcription start site of this gene was identified and studied [22].
• METHODS: A total of 353 patients with IDDM who had completed the first 6 years of follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study were included in this analysis [23].

Anatomical context of Diabetes Complications

• In both type 1 and type 2 diabetes, the late diabetic complications in nerve, vascular endothelium, and kidney arise from chronic elevations of glucose and possibly other metabolites including free fatty acids (FFA) [15].
• Recent demonstrations of enhanced ROS production in mitochondria of bovine aortic endothelial cells exposed to high glucose have supported the idea that the pathogenesis of diabetic complications may involve ROS-induced GAPDH inhibition [24].
• The function of the vas deferens protein is unknown; however, aldose reductase is an NADPH-dependent monomeric oxidoreductase implicated in the pathogenesis of diabetic complications [25].
• Angiotensin II, through its effects on contractility, growth, and the sympathetic nervous system, may potentially play a key role in this pathologic process and, thus, contribute to the development of these cardiovascular and renal complications of diabetes mellitus [26].
• CONCLUSION/INTERPRETATION: In Type II diabetes impaired neutrophil actin polymerisation leads to persistent expression of CD11b and reduced exocytosis of primary granules and could contribute to the pathogenesis of diabetic complications [27].

Gene context of Diabetes Complications

• The physiological impact of basal AR2 expression in such cells may be limited to hyperglycemic states in which AR2 promotes pathological polyol accumulation, a mechanism invoked in the pathogenesis of diabetic complications [28].
• Thus, VEGF therapy may be useful in the treatment of diabetic complications characterized by impaired neovascularization [29].
• The aim of the present study was to investigate the possible association of plasma CTGF levels in type 1 diabetic patients with markers relevant to development of diabetes complications [30].
• Consequently, extrapolations concerning the pathogenetic role of the IGF/IGFBP system in the development of diabetic complications at the tissue level remain speculative [31].
• Aldose reductase (AR), the first enzyme in the polyol pathway, has been implicated in the pathogenesis of diabetic complications, although its physiological role is unclear [32].

Analytical, diagnostic and therapeutic context of Diabetes Complications

• We have investigated the conversion of protein-Amadori intermediate to protein-AGE and the mechanism of its inhibition by pyridoxamine (PM), a potent AGE inhibitor that has been shown to prevent diabetic complications in animal models [33].
• Based on previous epidemiological studies relating plasma glucose to chronic diabetic complications, GHb as measured in this study would properly identify the vast majority of subjects at risk [34].
• All individuals underwent an oral glucose tolerance test and other clinical measurements aimed at investigating the underlying metabolic defect and the presence of diabetic complications [35].
• The studies presented here demonstrate that aminoguanidine, an experimental therapeutic currently in clinical trials to prevent diabetic complications, is cerebroprotective in focal cerebral infarction [36].
• Lipoprotein(a) concentration shows little relationship to IDDM complications in the Pittsburgh Epidemiology of Diabetes Complications Study cohort [37].

References