Advanced Glycation End Products in Nondiabetic Patients With Coronary Artery Disease

Kanauchi, Masao; Tsujimoto, Nobuhiro; Hashimoto, Takeji

doi:10.2337/diacare.24.9.1620

Cited by 108 publications

(94 citation statements)

References 15 publications

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“…A1C could be considered a good marker for glycated proteins, which play a contributory role in atherosclerosis (23,24) not only in diabetic but also in nondiabetic subjects (25). This is supported by the findings that even nondiabetic subjects with CAD have increased levels of A1C (26).…”

Section: Discussionsupporting

confidence: 78%

Association of A1C With Cardiovascular Disease and Metabolic Syndrome in Asian Indians With Normal Glucose Tolerance

et al. 2007

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OBJECTIVE -This study examines the association of A1C with cardiovascular disease (CVD) risk factors, coronary artery disease (CAD), and metabolic syndrome in Asian Indians with normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS-This cross-sectional study recruited subjects from phase III of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study in a representative population of Chennai (formerly Madras) in South India, conducted between January 2003 and June 2004. Included were 1,644 subjects with NGT, i.e., fasting plasma glucose Ͻ100 mg/dl (5.6 mmol/l) and 2-h postload plasma glucose Ͻ140 mg/dl (7.8 mmol/l). A1C was measured using the Biorad Variant machine. Metabolic syndrome was defined based on modified Adult Treatment Panel III guidelines.RESULTS -The mean Ϯ SD A1C value in the study cohort was 5.5 Ϯ 0.4%. A1C showed a significant association with BMI (␤ ϭ 0.017, P Ͻ 0.001), systolic (␤ ϭ 0.002, P ϭ 0.028) and diastolic (␤ ϭ 0.202, P ϭ 0.017) blood pressure, waist circumference (␤ ϭ 0.007, P Ͻ 0.001), serum cholesterol (␤ ϭ 0.002, P Ͻ 0.001), triglycerides (␤ ϭ 0.001, P Ͻ 0.001), LDL cholesterol (␤ ϭ 0.002, P Ͻ 0.001), fasting insulin (␤ ϭ 0.009, P Ͻ 0.001), and homeostasis model assessment of insulin resistance (␤ ϭ 0.047, P Ͻ 0.001) after adjusting for age and sex. Regression analysis showed that A1C had a strong association with metabolic syndrome that persisted after adjusting for age and sex (odds ratio [OR] 2.9 [95% CI 2.08 -4.00]; P Ͻ 0.001). A1C also had a strong association with CAD (2.6 [1.23-5.63]; P ϭ 0.01), but the significance was lost when adjusted for age and sex.CONCLUSIONS -There is a strong association of A1C with prevalent CVD risk factors in Asian-Indian subjects with NGT. Diabetes Care 30:1527-1532, 2007T he DCCT (Diabetes Control and Complications Trial) and UKPDS (UK Prospective Diabetes Study) demonstrated the importance of A1C in the development of long-term diabetes microvascular complications (1,2). Further, both studies elegantly demonstrated significant reductions in the risk of developing microvascular complications for every percentage of reduction in A1C levels (1,2). However, the association of A1C with cardiovascular disease (CVD) is less clear (3)(4)(5)(6)(7)(8).CVD is the principal cause of mortality globally, particularly in type 2 diabetic subjects, as their CVD mortality risk is equal to that of subjects without diabetes who had a previous episode of myocardial infarction (9). Recent prospective studies have shown that A1C is associated with CVD and mortality (10). This association has also recently been extended to nondiabetic subjects, as the relationship of CVD with glycemia is believed to be a continuum without a threshold effect (5-8).However, there is uncertainty as to the nature of the relationship, as some studies report no statistically significant association (3) between A1C and CVD in nondiabetic males while others do (4 -8).Asian Indians are known to have very high rates of premature coronary artery disease (CAD) and diab...

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Section: Discussionsupporting

confidence: 78%

Association of A1C With Cardiovascular Disease and Metabolic Syndrome in Asian Indians With Normal Glucose Tolerance

et al. 2007

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“…We also did not find a significant relationship between AGEs and HbA 1c . This lack of correlation between AGEs and HbA 1c has also been reported by other groups and may be caused by a different turnover and/or a time lag in AGE production and removal (24,25). In addition to the association between AGEs and CRP, our data showed that BMI and IL-6 were also important determinants of circulating CRP.…”

supporting

confidence: 44%

Association Between Acute-Phase Reactants and Advanced Glycation End Products in Type 2 Diabetes

et al. 2004

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OBJECTIVE -Type 2 diabetes is associated with chronic low-grade inflammation, but the underlying mechanism(s) is not well understood. Because in vitro studies have shown that advanced glycation end products (AGEs) can trigger inflammatory responses, the present study has investigated whether serum concentration of AGEs is an important determinant of circulating levels of inflammatory markers, like C-reactive protein (CRP), in type 2 diabetic patients.RESEARCH DESIGN AND METHODS -Diabetic patients (n ϭ 210) and healthy control subjects (n ϭ 110) of similar BMI were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit anti-sera raised against AGE-RNase. Plasma high-sensitivity CRP was measured by an immunoturbidimetric assay and interleukin (IL)-6 by enzyme-linked immunosorbent assay. 48 -0.84], respectively, P Ͻ 0.01) were also higher in diabetic patients than in control subjects. In the diabetic patients, log(CRP) correlated with AGEs (r ϭ 0.22, P ϭ 0.002) and with log(IL-6) (r ϭ 0.29, P Ͻ 0.001). Forward stepwise linear regression analysis showed that BMI, log(IL-6), and AGEs were significant independent determinants of log(CRP) in the diabetic patients, accounting for 17, 12, and 10% of the variation in log(CRP), respectively. RESULTSCONCLUSIONS -Serum concentration of AGEs is increased in patients with diabetes and is an independent determinant of plasma CRP levels. Subclinical inflammation in these patients may therefore be partly due to activation of the inflammatory response by AGEs. Diabetes Care 27:223-228, 2004A ccumulating evidence suggests that type 2 diabetes is associated with chronic low-grade inflammation. Cross-sectional studies have shown that concentrations of inflammatory markers are elevated in patients with type 2 diabetes and in those with the metabolic syndrome. Abnormalities include small but definite increases of serum or plasma concentrations of several acute-phase proteins, including C-reactive protein (CRP), serum amyloid A, fibrinogen, ␣1-acid glycoprotein, and plasminogen activator inhibitor-1 (1-5). The underlying mechanism(s) for the augmented acute-phase response is not well understood, and the stimulus for this response is unknown. A number of hypotheses have been put forward, and these include obesity and insulin resistance, preexisting atherosclerosis and/or diabetic complications, and maladaptation of the normal innate immune system response to environmental threats (6 -8). Immune abnormalities or chronic slow infections with concomitant immune activation may also occur as a result of metabolic disturbance in type 2 diabetes rather than representing its cause. It has, however, been suggested by Pickup and Crook (6) that hyperglycemia is unlikely to have a major effect on the acutephase response in type 2 diabetes. This is based on their observations that there was a lack of correlation between serum sialic acid concentrations and glycemic control in type 2 diabetes (9) and that sialic acid concentration was normal in u...

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“…However, the identification of AGEs in the atherosclerotic plaques of nondiabetic patients with coronary artery disease have magnified the importance of AGEs and oxidative stress in accelerating atherosclerosis 41. AGEs from long‐lived proteins such as collagens42 predict future progression of microvascular disease, progression of carotid intima‐media thickness, left ventricular mass, and the severity of coronary artery calcium 43.…”

Section: Discussionmentioning

confidence: 99%

Skin Autofluorescence–Indicated Advanced Glycation End Products as Predictors of Cardiovascular and All‐Cause Mortality in High‐Risk Subjects: A Systematic Review and Meta‐analysis

Cavero‐Redondo

Soriano-Cano

Álvarez‐Bueno

et al. 2018

JAHA

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BackgroundChronic deposits of advanced glycation end products produced by enzymatic glycation have been suggested as predictors of atherosclerotic‐related disorders. This study aimed to estimate the relationship between advanced glycation end products indicated by skin autofluorescence levels and the risk of cardiovascular and all‐cause mortality based on data from observational studies.Methods and ResultsWe systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Web of Science databases from their inceptions until November 2017 for observational studies addressing the association of advanced glycation end products by skin autofluorescence levels with cardiovascular and all‐cause mortality. The DerSimonian and Laird random‐effects method was used to compute pooled estimates of hazard ratios and their respective 95% confidence intervals for the risk of cardiovascular and all‐cause mortality associated with levels of advanced glycation end products by skin autofluorescence. Ten published studies were included in the systematic review and meta‐analysis. Higher skin autofluorescence levels were significantly associated with a higher pooled risk estimate for cardiovascular mortality (hazard ratio: 2.06; 95% confidence interval, 1.58–2.67), which might not be important to moderate heterogeneity (I2=34.7%; P=0.163), and for all‐cause mortality (hazard ratio: 1.91; 95% confidence interval, 1.42–2.56) with substantial heterogeneity (I2=60.8%; P=0.0.18).ConclusionsOur data suggest that skin autofluorescence levels could be considered predictors of all‐cause mortality and cardiovascular mortality in patients at high and very high risk.

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Advanced Glycation End Products in Nondiabetic Patients With Coronary Artery Disease

Cited by 108 publications

References 15 publications

Association of A1C With Cardiovascular Disease and Metabolic Syndrome in Asian Indians With Normal Glucose Tolerance

Association of A1C With Cardiovascular Disease and Metabolic Syndrome in Asian Indians With Normal Glucose Tolerance

Association Between Acute-Phase Reactants and Advanced Glycation End Products in Type 2 Diabetes

Skin Autofluorescence–Indicated Advanced Glycation End Products as Predictors of Cardiovascular and All‐Cause Mortality in High‐Risk Subjects: A Systematic Review and Meta‐analysis

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