Cardiovascular effects of acute hyperglycemia pathophysiological underpinnings

Warwick Medical School, Clinical Science Research Institute, University Hospital -Coventry, CV2 2DX, UK.
Diabetes & Vascular Disease Research (Impact Factor: 3.04). 12/2008; 5(4):260-8. DOI: 10.3132/dvdr.2008.038
Source: PubMed

ABSTRACT High admission blood glucose levels after acute myocardial infarction are common and are associated with an increased risk of death in subjects with and without diabetes. In this review, the possible toxic effects of acute hyperglycaemia are discussed as a possible explanation for the worse prognosis in subjects with myocardial infarction and concomitant hyperglycaemia. In particular, evidence supporting the hypothesis that acute hyperglycaemia may favour the appearance of cardiovascular disease through the generation of oxidative stress is presented.

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    • "Mechanisms by which glucose abnormalities may be a causal factor for poor outcome in patients undergoing PCI remain not completely understood. Hyperglycemia causes release of proinflammatory cytokines (IL-6, IL-8, IL-18, and TNF-í µí»¼), diminished bioavailability of nitric oxide with attendant endothelial dysfunction, and increased production of oxygen-derived free radicals with enhanced oxidative stress [11] [12] [27]. All these mechanisms have also been described in the pathogenesis of renal damage after contrast media exposure [28]; thus, acute hyperglycemia may exacerbate the deleterious effects of contrast agents on the kidney. "
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    ABSTRACT: Poor glycemic control is associated with unfavorable outcome in patients undergoing percutaneous coronary intervention (PCI), irrespective of diabetes mellitus. However a complete assessment of glycemic status may not be fully described by glycated hemoglobin or fasting blood glucose levels, whereas daily glycemic fluctuations may influence cardiovascular risk and have even more deleterious effects than sustained hyperglycemia. Thus, this paper investigated the effectiveness of a continuous glucose monitoring (CGM), registering the mean level of glycemic values but also the extent of glucose excursions during coronary revascularization, in detecting periprocedural outcome such as renal or myocardial damage, assessed by serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and troponin I levels. High glycemic variability (GV) has been associated with worse postprocedural creatinine and NGAL variations. Moreover, GV, and predominantly hypoglycemic variations, has been observed to increase in patients with periprocedural myocardial infarction. Thus, our study investigated the usefulness of CGM in the setting of PCI where an optimal glycemic control should be achieved in order to prevent complications and improve outcome.
    Journal of Diabetes Research 01/2015; 2015:250201. DOI:10.1155/2015/250201 · 3.54 Impact Factor
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    • "PPGH now has been established as one of the earliest detectable abnormalities expressed in ensuing diabetes mellitus (Gerich, 1996), better predictor of progression of diabetes (Davidson, 2003), cardiovascular diseases (CVD) and an independent risk factor for atherosclerosis (Boutati and Raptis, 2004). It has also been implicated in inducing oxidative stress (Ceriello, 2008) that is recognized as a major pathophysiological link between cardiovascular disorders and diabetes (Giugliano et al., 1996). Therefore, mitigation of rapid postprandial hyperglycemic excursion "
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    ABSTRACT: A series of furanochalcone derivatives have been designed and synthesized. Molecular modeling studies were carried out to probe into the mechanism of binding of chalcone inhibitors and understand the structure–activity relationship to identify the contribution of scaffolds and groups in the synthesized analogs to biological activity. The three-dimensional model of α-glucosidase was constructed based on the crystal structure family 31 α-glycosidase (PDB 1XSI) using Modeller9v5. Docking of the inhibitors on the built homology model revealed interactions in the active site region mostly with Asp 252, Tyr254, Gln523, and Arg571. 2D-QSAR models were generated with CODESSA using Heuristic method. The best predictive model was generated using three descriptors that gave a correlation co-efficient (r 2) 0.9886 and cross-validate (r 2) 0.9338. The synthesized compounds were screened against the α-glucosidase inhibition and DPPH radical scavenging properties. All the synthetic compounds displayed varying degrees of α-glucosidase inhibitory and DPPH scavenging activities. Compound 8c was found most potent α-glucosidase inhibitor though; it could not display DPPH scavenging activity. When tested in vivo for antihyperglycemic activity in starch-loaded Wistar rats, 8c was equally effective in reducing time-dependent hyperglycemia as to the standard drug, Acarbose. Compound 8c may serve as an interesting compound for the development of therapeutics targeted against diet-induced hyperglycemia in diabetes. KeywordsFuranochalcones–DPPH free radical scavenging activity–α-Glucosidase inhibitory activity–Molecular modeling–QSAR
    Medicinal Chemistry Research 06/2012; DOI 10.1007/s00044-011-9583-7(6):1-15. DOI:10.1007/s00044-011-9583-7 · 1.61 Impact Factor
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    • "Slowing down of the digestion and absorption of dietary carbohydrates using a-glucosidase inhibitors has, thus, proved to be a promising therapeutic strategy for reducing risk of diabetes and the consequential diseases. Further, a rich meal also causes increased susceptibility of the organism toward oxidative damage, known as postprandial oxidative stress (PPOS), characterized by overt generation of free radicals that induce oxidative biological damage to biomolecules causing free radical mediated diseases (Ceriello, 2008; Sies et al., 2005), including diabetes. Antioxidants that scavenge free radicals are now known to possess preventive as well as therapeutic potential (Halliwell, 1994; Halliwell, 1999; Noguchi and Nikki, 2000; Prasad et al., 1999; Tiwari, 1999; Visioli et al., 2000a; b; Winyard and Blake, 1997), against free radical mediated diseases. "
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    ABSTRACT: α-Glucosidase inhibition and DPPH free radical scavenging by 5-bromosalicylaldehyde and some Schiff bases have been measured. 5-Bromosalicylaldehyde shows lowest IC50 value (8.80μM) for α-glucosidase inhibition and also shows good results in invivo experiments for antihyperglycemic potential. Keywordsα-Glucosidase inhibition–DPPH free radical scavenging–Antihyperglycemic activity Schiff bases–5-Bromosalicylaldehyde
    Medicinal Chemistry Research 12/2011; 20(9):1431-1437. DOI:10.1007/s00044-010-9377-3 · 1.61 Impact Factor
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