Plasma low-molecular weight fluorescence in type 1 diabetes mellitus
ABSTRACT Characteristic tissue fluorescence is associated with advanced glycation end product (AGE) accumulation in experimental diabetes models, but its utility in patients with type 1 diabetes remains to be established. We studied 148 patients with type 1 diabetes and 77 healthy age-matched control subjects. Low-molecular weight (LMW) fluorophore levels were estimated in plasma samples obtained after an overnight fast. Intra- and interassay coefficients of variation were 4.7% and 6.4%, respectively. LMW fluorophore levels were significantly higher in patients with diabetes than in control subjects (6.3 +/- 0.6 AU/mL vs. 4.1 +/- 0.3; P = 0.007). However, all of this difference came from patients with microvascular complications (n = 67, 7.5 +/- 1.3). There was no significant difference in LMW fluorescence between complication-free patients (4.4 +/- 0.2) and control subjects (P > 0.05). On multivariate analysis, LMW fluorophores correlated with measures of renal function (P < 0.05) but not with diabetes per se. In addition, there was no correlation between LMW fluorophores and the markers of oxidative stress or systemic inflammation. Longitudinal and interventional studies are required to determine whether the association between LMW fluorophores and nephropathy is cause or effect.
SourceAvailable from: Andrew E Newcomb[Show abstract] [Hide abstract]
ABSTRACT: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. The patients were aged 43-78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e' (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e' was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e' (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e' remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate. Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.PLoS ONE 11/2012; 7(11):e49813. DOI:10.1371/journal.pone.0049813 · 3.53 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Advanced glycation end products (AGEs) are involved in the occurrence of vascular complications in diabetes. The present study was undertaken to investigate the level of low-molecular weight products of AGEs (LMW-AGEs) in relation to microvascular complications in type 1 diabetes, and the possible relationship with nitric oxide (NO) as a marker of endothelial function. Patients with normal renal function (NRF) were classified into two groups: (1) without, and (2) with diabetic neuropathy; and patients with renal impairment also into two groups: (3) diabetic renal disease, and (4) end-stage renal disease. The fluorescence of LMW-AGEs and measurement of NO metabolites was assessed in 277 serum samples. In addition, multiple regression analysis was performed. In group 1, LMW-AGEs level (9.3±1.1 AF%) was higher than in the control group (2.4±0.3 AF%). A trend in the increase of LMW-AGEs with neuropathy (29.7±5.5 AF%, group 2), and further with renal impairment (47.0±8.0, group 3 and 137.8±25.5 AF%, group 4), was observed. In multivariate regression analysis LMW-AGEs were associated with NO metabolites in group 2. In NRF patients, diabetic neuropathy was significantly correlated with LMW-AGEs and NO metabolites, independently of serum creatinine and duration of diabetes. This relationship suggests that the NO and LMW-AGEs’ actions (possibly synergistic) in endothelial activation possess a role in the initiation and development of diabetic microvascular complications.Central European Journal of Biology 08/2008; 3(3):243-249. DOI:10.2478/s11535-008-0019-4 · 0.63 Impact Factor