imidazolone and Diabetic-Retinopathy

Six skin collagen advanced glycation end products (AGEs) originally measured near to the time of the Diabetes Control and Complications Trial (DCCT) closeout in 1993 may contribute to the "metabolic memory" phenomenon reported in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. We have now investigated whether the addition of four originally unavailable AGEs (i.e., glucosepane [GSPNE], hydroimidazolones of methylglyoxal [MG-H1] and glyoxal, and carboxyethyl-lysine) improves associations with incident retinopathy, nephropathy, and neuropathy events during 13-17 years after DCCT. The complete 10-AGE panel is associated with three-step Early Treatment of Diabetic Retinopathy Study scale worsening of retinopathy (P ≤ 0.002), independent of either mean DCCT or EDIC study A1C level. GSPNE and fructose-lysine (furosine [FUR]) correlate with retinopathy progression, independently of A1C level. The complete panel also correlates with microalbuminuria (P = 0.008) and FUR with nephropathy independently of A1C level (P ≤ 0.02). Neuropathy correlates with the complete panel despite adjustment for A1C level (P ≤ 0.005). MG-H1 and FUR are dominant, independent of A1C level (P < 0.0001), whereas A1C loses significance after adjustment for the AGEs. Overall, the added set of four AGEs enhances the association of the original panel with progression risk of retinopathy and neuropathy (P < 0.04) but not nephropathy, while GSPNE and MG-H1 emerge as the principal new risk factors. Skin AGEs are robust long-term markers of microvascular disease progression, emphasizing the importance of early and sustained implementation of intensive therapy.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Disease Progression; Female; Glycation End Products, Advanced; Humans; Imidazoles; Logistic Models; Male; Microvessels; Multivariate Analysis; Pyruvaldehyde; Skin; Young Adult

We aimed to investigate associations between serum levels of the advanced glycation endproduct methylglyoxal-derived hydroimidazolone (MG-H1) and retinopathy in a sample of patients with type 1 diabetes.. We conducted a cross-sectional study in a Scandinavian ophthalmology outpatient clinic on 61 randomly selected patients with type 1 diabetes. Blood samples and retinal photographs were taken at the same visit. Serum levels of hydroimidazolone immunoreactivity were determined using an immunoassay, and levels of retinopathy were determined from seven standard field stereo photographs of each eye according to the ETDRS method. Results were compared between patients with and without retinopathy.. Hydroimidazolone quartiles were significantly associated with retinopathy (p = 0.013). The most profound increase in occurrence of retinopathy was observed from the lowest to the second-lowest hydroimidazolone quartile. Adjusted for duration of diabetes using logistic regression, a significant difference in the presence of retinopathy was found when comparing the lowest quartile with the rest (p = 0.022).. In our patients with type 1 diabetes, serum levels of hydroimidazolone were found to be associated with retinopathy. This is in keeping with findings in a larger sample of patients with type 2 diabetes.

Topics: Adolescent; Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Fundus Oculi; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Imidazoles; Immunoassay; Male; Middle Aged; Prevalence; Pyruvaldehyde; Young Adult

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