imidazolone and Diabetes-Mellitus--Type-2

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase, being involved in endothelial dysfunction. Furthermore, ADMA levels have been shown to predict future cardiovascular events in patients with coronary risk factors, such as diabetes and hypertension. We have previously found that glyceraldehyde-derived advanced glycation end products (glycer-AGEs) stimulate ADMA generation

Topics: Aged; Arginine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Imidazoles; Inflammation; Male; Middle Aged; Protein Binding; Pyruvaldehyde; Vascular Stiffness

Topics: Adult; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Glycation End Products, Advanced; Humans; Imidazoles; Indians, North American; Kidney; Kidney Glomerulus; Losartan; Lysine; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Pyruvaldehyde

To determine whether plasma levels of advanced glycation end products and oxidation products play a role in the development of atherosclerosis in patients with type 2 diabetes (T2D) over nearly 10 years of the VA Diabetes Trial and Follow-up Study.. Baseline plasma levels of methylglyoxal hydroimidazolone, Nε-carboxymethyl lysine, Nε-carboxyethyl lysine (CEL), 3-deoxyglucosone hydroimidazolone and glyoxal hydroimidazolone (G-H1), 2-aminoadipic acid (2-AAA), and methionine sulfoxide were measured in a total of 411 participants, who underwent ultrasound assessment of carotid intima-media thickness (CIMT), and computed tomography scanning of coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) after an average of 10 years of follow-up.. In risk factor-adjusted multivariable regression models, G-H1 was associated with the extent of CIMT and CAC. In addition, 2-AAA was strongly associated with the extent of CAC, and CEL was strongly associated with the extent of AAC. The combination of specific advanced glycation end products and oxidation products (G-H1 and 2-AAA) was strongly associated with all measures of subclinical atherosclerosis.. Specific advanced glycation end products and metabolic oxidation products are associated with the severity of subclinical atherosclerosis over the long term and may play an important role in the "negative metabolic memory" of macrovascular complications in people with long-standing T2D.

Topics: Aged; Atherosclerosis; Blood Glucose; Carotid Intima-Media Thickness; Cholesterol; Deoxyglucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycation End Products, Advanced; Humans; Imidazoles; Lysine; Male; Middle Aged; Oxidation-Reduction; Pyruvaldehyde; Triglycerides

To investigate the association of the levels of methylglyoxal-derived hydroimidazolone AGE modified proteins (MG-H1-AGE) with cardiovascular disease (CVD) mortality in an 18-year follow-up study in Finnish nondiabetic and diabetic subjects.. The study design was a nested case-control study. Serum MG-H1-AGE levels in samples drawn at baseline were measured with a DELFIA type immunoassay in 220 diabetic subjects and 61 nondiabetic subjects who died from CVD during the follow-up, and age- and gender-matched 157 diabetic subjects and 159 nondiabetic subjects who did not die from CVD.. In type 2 diabetic subjects serum MG-H1-AGE levels were similar in subjects who died from CVD and in subjects who did not, 32.6 (24.6-42.1) (median (interquartile range)) vs. 31.3 (22.5-40.7)U/mL (p=0.281). In nondiabetic subjects serum MG-H1 levels were significantly higher in subjects who died from CVD than in subjects who were alive, 35.4 (28.1-44.7) vs. 31.3 (24.2-38.6)U/mL (p=0.025). Corresponding MG-H1 levels were 41.2 (35.6-58.7) vs. 31.1 (26.7-35.7)U/mL, p=0.003, in women, and 34.4 (26.3-41.2) vs. 32.0 (22.8-40.3)U/mL, p=0.270, in men. Multivariate logistic regression analysis showed a significant association of serum levels of MG-H1-AGE with CVD mortality in nondiabetic women (adjusted p=0.021), but not in nondiabetic men.. Our 18-year follow-up study shows that high baseline serum levels of MG-H1 type of AGE modified proteins were associated with CVD mortality in nondiabetic women, but not in nondiabetic men or in diabetic subjects.

Topics: Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Female; Finland; Follow-Up Studies; Glycation End Products, Advanced; Humans; Imidazoles; Male; Middle Aged; Odds Ratio; Pyruvaldehyde; Regression Analysis; Sex Factors

As advanced glycation endproducts (AGEs) and the vitreous body are both considered to be involved in the development of diabetic retinopathy and hydroimidazolone is one of the most prominent AGEs, we compared vitreous and serum hydroimidazolone in diabetes patients with proliferative diabetic retinopathy (PDR) to levels in non-diabetes controls, co-measuring vitreous albumin and vascular endothelial growth factor (VEGF).. In a cross-sectional case-control study design, we used immunoassays to compare vitreous and serum hydroimidazolone and VEGF levels in 23 consecutive type 2 diabetes mellitus patients with a median known diabetes duration of 12 years (range 1-38 years) with those in 32 non-diabetes age-matched controls undergoing vitrectomy.. Vitreous hydroimidazolone was increased in the PDR group (median 1.3 U/ml, range 0.5-3.3 U/ml) compared with controls (median 0.8 U/ml, 0.5-2.5 U/ml) (p = 0.026). Hydroimidazolone levels in serum and vitreous correlated (r = 0.49, p = 0.019). In PDR, vitreous VEGF levels were increased (median 1600 pg/ml, range 20-14 700 pg/ml) compared with controls (median 7 pg/ml, range 2-500 pg/ml) (p < 0.001). Similarly, vitreous albumin concentration was increased in PDR (median 1.6 g/l, range 0.7-3.0 g/l) compared with controls (median 0.3 g/l, range 0.08-1.9 g/l) (p < 0.001). Albumin could not explain the differences in vitreous VEGF levels in a logistic regression analysis. No correlation was found between vitreous levels of VEGF and hydroimidazolone (r = 0.12, p = 0.59).. Increased vitreous hydroimidazolone is associated with diabetic retinopathy, possibly due to a blood-retinal barrier breakdown. Irrespective of origin, it may add to the ocular damage and needs further causal investigation. Increased VEGF in diabetic vitreous is probably of intraocular origin. It is not associated with vitreous hydroimidazolone.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Blood-Retinal Barrier; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Fluoroimmunoassay; Humans; Imidazoles; Male; Middle Aged; Vascular Endothelial Growth Factor A; Vitreous Body

Advanced glycation end products (AGEs) are thought to play a major pathogenic role in diabetic retinopathy. The most important AGE is unknown, but as increased serum methylglyoxal-derived hydroimidazolone has been demonstrated in patients with type 2 diabetes mellitus, the aim of the present study was to elucidate possible associations between serum levels of hydroimidazolone and retinopathy in patients with type 2 diabetes mellitus. We recruited 227 patients with type 2 diabetes mellitus and retinopathy ranging from none to proliferative. Level of retinopathy was determined from 7 standard field stereo photographs per eye according to the Early Treatment Diabetic Retinopathy Study. The patients were 66 +/- 11 years old, with a known diabetes duration of 14 +/- 9 years. Serum levels of hydroimidazolone were determined with a competitive immunoassay. Serum levels of hydroimidazolone were increased in nonproliferative (median, 4.50 U/mL; interquartile range, 3.69-5.77 U/mL) and proliferative retinopathy (median, 4.88 U/mL; interquartile range, 3.70-6.52 U/mL) compared with patients without retinopathy (median, 4.02 U/mL; interquartile range, 3.47-4.88 U/mL) (P = .008 and .002, respectively). There was no association between hydroimidazolone and hemoglobin A1c (r = 0.04, P = .57). In addition, patients with proliferative retinopathy and a relatively short known duration of diabetes, that is, less than the median of 14 years, had increased serum levels of hydroimidazolone (median, 6.91 U/mL; interquartile range, 4.70-8.91 U/mL) compared with those with nonproliferative retinopathy (median, 4.34; interquartile range, 3.86-5.53U/mL, P = .015). Serum levels of hydroimidazolone are increased in type 2 diabetic patients with retinopathy. This association is independent of hitherto known associated factors, such as hemoglobin A1c.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Creatinine; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Imidazoles; Logistic Models; Male; Middle Aged; Visual Acuity

A time-delayed fluorescence immunoassay was developed for the determination of serum levels of methylglyoxal (MG)-derived hydroimidazolone using a monoclonal antiserum raised against Nalpha-acetyl-Ndelta-(5-hydro-5-methyl)-4-imidazolone, Europium-labeled anti-mouse IgG antiserum as indicator, and MG modified bovine serum albumin (BSA) as standard. Serum levels of hydroimidazolone were measured in 45 patients with type 2 diabetes aged 59.4 +/- 6.1 (mean +/- SD) years and with duration of diabetes of 7.3 +/- 3.1 years, and in 19 nondiabetic controls aged 56.3 +/- 4.3 years. The serum levels of hydroimidazolone were significantly higher in patients compared to controls: median, 3.0 (5-95 percentile, 1.6 to 5.4) U/mg protein versus 1.9 (1.2 to 2.8) U/mg protein (P =.0005). Significant positive correlations were observed between the serum levels of hydroimidazolone and serum levels of advanced glycation end products (AGEs), measured with a polyclonal anti-AGE antibody: r = 0.59 for patients (P <.0001), and r = 0.65 for controls (P =.002). Similarly, significant correlations were also found between serum levels of hydroimidazolone and N(epsilon)-(carboxymethyl)-lysine (CML): r = 0.36 in patients and r = 0.55 for controls (both P =.02). Serum hydroimidazolone levels did not correlate with fasting plasma glucose or hemoglobin A(1c) (HbA(1c)) levels. The observed differences between patients with diabetes and nondiabetic controls seem to be comparable to differences measured for other AGE compounds.

Topics: Diabetes Mellitus, Type 2; Humans; Imidazoles; Immunoassay; Lysine; Pyruvaldehyde; Sensitivity and Specificity