Increased serum concentrations of advanced glycation end products: a marker of coronary artery disease activity in type 2 diabetic patients

Kiuchi, Kaname; Nejima, Jun; Tajiri, Tatsuro; Ohta, Masahito; Hashimoto, Hidekazu

doi:10.1136/heart.85.1.87

Cited by 101 publications

(77 citation statements)

References 18 publications

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“…Compared with the use of samples from skin biopsies for measurement of AGEs, serum samples are simple, and with standardisation they could become a useful clinical tool. Previous cross-sectional studies have demonstrated increased serum AGE levels in patients with type 2 diabetes and CVD [18,29]. Our study shows that high serum AGE levels predict total, CVD and CHD mortality in type 2 diabetic patients during long-term follow-up.…”

Section: Discussionsupporting

confidence: 49%

“…Experimental studies in animals and in humans have shown that treatments that break the crosslinks result in greater vascular compliance [16,17]. In a cross-sectional study, elevated levels of circulating AGEs correlated with the extent of coronary artery occlusion in type 2 diabetic patients [18]. We recently reported that high serum levels of AGEs predict mortality from CHD in nondiabetic women, but not in non-diabetic men [19].…”

Section: Introductionmentioning

confidence: 99%

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Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

et al. 2007

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Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45-64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p=0.002) and CVD mortality (p=0.021) in women, but not in men. Serum levels of AGEs in the highest sexspecific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14-1.99; p=0.004), CVD (HR 1.56; 95% CI 1.12-2.19; p=0.009), and CHD (HR 1.68; 95% CI 1.11-2.52; p=0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

et al. 2007

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“…In diabetes mellitus, AGE accumulation in skin collagen is correlated both with the duration and severity of hyperglycaemia, and with the presence of long-term complications [6,7,8,12,13,14,15]. In a DCCT substudy, skin AGE levels explained 19 to 36% of the variance in the incidence of long-term diabetic complications in intensively treated patients, and 14 to 51% in conventionally treated patients [8].…”

Section: Introductionmentioning

confidence: 99%

Simple non-invasive assessment of advanced glycation endproduct accumulation

Meerwaldt¹,

Graaff

Oomen³

et al. 2004

Diabetologia

654

815

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Aims/hypothesis. The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. Methods. Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age-and sexmatched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N ε -(carboxymethyl)-lysine (CML) and N ε -(carboxyethyl)lysine (CEL).Results. Autofluorescence correlated with CLF, pentosidine, CML, and CEL (r=0.47-0.62, p≤0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were above the 95% CI of the mean value in control subjects, and correlated with age, diabetes duration, mean HbA 1 c of the previous year and creatinine levels. Conclusions/interpretation. The AFR offers a simple alternative to invasive measurement of AGE accumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation.

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“…Second, cTnT release from injured myocardium may have a longer circulating half-life compared with cTnI because of advanced glycation end products known to accumulate in diabetic patients with renal disease. 28 However, future studies need to evaluate this concept. Third, two small studies have suggested that cTnI decreases after dialysis, either directly attributable to removal by dialysis or indirectly by degradation of the labile cTnI molecule.…”

Section: Apple Et Al Prognostic Value Of Troponin In Renal Disease 2943mentioning

confidence: 99%

Predictive Value of Cardiac Troponin I and T for Subsequent Death in End-Stage Renal Disease

et al. 2002

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Background-This study determined the prevalence of increased cardiac troponin I (cTnI) and T (cTnT) in end-stage renal disease (ESRD) patients and whether an increased troponin was predictive of death. Methods and Results-Serum was obtained from 733 ESRD patients and measured for cTnI and cTnT. Relative risks were estimated using Cox proportional hazards regressions univariately and adjusted for age, time on dialysis, and coronary artery disease. Kaplan-Meier curves compared time to event data between groups. Greater percentages of patients had an increased cTnT versus cTnI at each cutoff, as follows: 99th percentile, 82% versus 6%; 10% coefficient of variation, 53% versus 1.0%; and receiver operator characteristic, 20% versus 0.4%. Increased versus normal cTnT was predictive of increased mortality using all cutoffs and only above the 99th percentile for cTnI. Two-year cumulative mortality rates increased (PϽ0.001) with changes in cTnT from normal (Ͻ0.01 g/L, 8.4%) to small (Ն0.01 to Ͻ0.04 g/L, 26%), moderate (Ն0.04 to Ͻ0.1 g/L, 39%), and large (Ն0.1 g/L, 47%) increases. Two-year mortalities were 30% for cTnI Ͻ0.1 g/L and 52% if Ն0.1 g/L. Univariate and adjusted relative risks of death associated with elevated (Ͼ99th percentile) cTnT were 5.0 (CI, 2.5 to 10; PϽ0.001) and 3.9 (CI, 1.9 to7.9; PϽ0.001) and cTnI were 2.0 (CI, 1.3 to 3.3; Pϭ0.008) and 2.1 (CI, 1.3 to 3.3; Pϭ0.007). Age, coronary artery disease, and time on dialysis were also independent predictors of mortality. Conclusions-Increases in cTnT and cTnI in ESRD patients show a 2-to 5-fold increase in mortality, with a greater number of patients having an increased cTnT.

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Increased serum concentrations of advanced glycation end products: a marker of coronary artery disease activity in type 2 diabetic patients

Cited by 101 publications

References 18 publications

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

Simple non-invasive assessment of advanced glycation endproduct accumulation

Predictive Value of Cardiac Troponin I and T for Subsequent Death in End-Stage Renal Disease

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