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  • 1
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    Glycated and Oxidized Protein Degradation Products Are Indicators of Fasting and Postprandial Hyperglycemia in Diabetes
    American Diabetes Association ; 2005
    In:  Diabetes Care Vol. 28, No. 10 ( 2005-10-01), p. 2465-2471
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 28, No. 10 ( 2005-10-01), p. 2465-2471
    Abstract: OBJECTIVE—To assess the relative importance of fasting and postprandial hyperglycemia to vascular dysfunction in diabetes, we have measured indicators of glycation, oxidative and nitrosative stress in subjects with type 1 diabetes, and different postprandial glucose patterns. RESEARCH DESIGN AND METHODS—Plasma and urinary levels of specific arginine- and lysine-derived advanced glycation end products, as well as oxidative and nitrosative products, were measured by liquid chromatography with triple quadrupole mass spectrometric detection (LC-MS/MS) after 2 months of treatment with insulin lispro or human regular insulin in 21 subjects participating in a cross-over study. Hb-bound early glycation (Amadori) products were also measured after each treatment period by high-performance liquid chromatography (fructosyl-valine Hb or HbA1c [A1C]:Diamat) and fructosyl-lysine Hb by LC-MS/MS (A1C:fructosyl-lysine). RESULTS—In diabetic patients, the concentrations of protein glycation and oxidation-free adducts increased up to 10-fold, while urinary excretion increased up to 15-fold. Decreasing postprandial hyperglycemia with lispro gave 10–20% decreases of the major free glycation adducts, hydroimidazolones derived from methylglyoxal and 3-deoxyglucosone, and glyoxal-derived Nε-carboxymethyl-lysine. No differences were observed in A1C:Diamat or A1C:fructosyl-lysine with lispro or regular insulin therapy in spite of significant decreases in postprandial glycemia with lispro. CONCLUSIONS—We conclude that the profound increases in proteolytic products of proteins modified by advanced glycation endproducts in diabetic patients are responsive to changes in mean hyperglycemia and also show responses to changes in postprandial hyperglycemia.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/diacare.28.10.2465
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2005
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  • 2
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    Ketosis Leads to Increased Methylglyoxal Production on the Atkins Diet
    Wiley ; 2005
    In:  Annals of the New York Academy of Sciences Vol. 1043, No. 1 ( 2005-06), p. 201-210
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1043, No. 1 ( 2005-06), p. 201-210
    Abstract: A bstract : In the popular and widely used Atkins diet, the body burns fat as its main fuel. This process produces ketosis and hence increased levels of β‐hydroxybutyrate (BOB) acetoacetate (AcAc) and its by‐products acetone and acetol. These products are potential precursors of the glycotoxin methylglyoxal. Since methylglyoxal and its byproducts are recognized as a significant cause of blood vessel and tissue damage, we measured methylglyoxal, acetone, and acetol in subjects on the Atkins diet. We found that by 14‐28 days, methylghyoxal levels rose 1.67‐fold ( P = 0.039 ) and acetol and acetone levels increased 2.7‐ and 6.12‐fold, respectively ( P = 0.012 and 0.028). Samples from subjects with ketosis showed even greater increases in methylglyoxal (2.12‐fold), as well as acetol and acetone, which increased 4.19‐ and 7.9‐fold, respectively; while no changes were seen in samples from noncompliant, nonketotic subjects. The increase in methylglyoxal implies that potential tissue and vascular damage can occur on the Atkins diet and should be considered when choosing a weight‐loss program.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Article
    DOI: 10.1196/annals.1333.025
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2005
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    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
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  • 3
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    Abstract P018: Advanced Glycation End Products And And Incident Cardiovascular Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 143, No. Suppl_1 ( 2021-05-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 143, No. Suppl_1 ( 2021-05-25)
    Abstract: Background: Advanced glycation end-products (AGEs) have been linked to cardiovascular disease (CVD) in populations with and without diabetes. There are limited data, however, regarding the longitudinal associations of the array of circulating AGE adducts with risk of CVD in the general population. We tested the hypothesis that major plasma AGEs, measured by gold-standard liquid chromatography/tandem mass spectrometry (LC/MS) are associated with incident CVD in subsets of two population-based cohort studies with different demographic and risk factor profiles. Methods: Analyses were performed in a case-cohort study of 2000 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and in a random cohort of 466 participants in the Cardiovascular Health Study (CHS). Five AGEs were measured by LC/MS: CML, 3DG-H, CEL, G-H1 and MG-H1. Incident CVD was defined as first occurrence of fatal or non-fatal stroke, myocardial infarction, or coronary heart disease death. Cox regression was used to examine associations between AGEs and CVD. Results: Participants in CHS were older than in MESA (median age=74 vs 65), had lower eGFR (67 vs 82 ml/min/1.73m 2 ) but higher CRP (median 2.53 vs 2.06 mg/L), and had substantially higher levels of all AGEs (Table) . During a median follow-up of 11 years in both cohorts, 439 (22%) participants in MESA and 200 (42%) in CHS developed incident CVD. In unadjusted models, all AGEs were strongly and significantly associated with incident CVD in MESA and CHS (Table). In multivariable adjusted models, CML, 3DG-H and a summary variable that accounted for all measured AGEs (PC1) were significantly associated with incident CVD in CHS but not in MESA. Conclusion: We found AGEs to be significantly associated with CVD in an older cohort, but not in a healthier middle-aged to older population that had lower systemic inflammation and lower baseline AGE concentrations. In the general population, AGEs may exert detrimental cardiovascular effects only at higher levels over longer cumulative exposure.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.143.suppl_1.P018
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 4
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    Methylglyoxal-derived advanced glycation end products contribute to negative cardiac remodeling and dysfunction post-myocardial infarction
    Springer Science and Business Media LLC ; 2017
    In:  Basic Research in Cardiology Vol. 112, No. 5 ( 2017-9)
    Details
    In: Basic Research in Cardiology, Springer Science and Business Media LLC, Vol. 112, No. 5 ( 2017-9)
    Type of Medium: Online Resource
    ISSN: 0300-8428 , 1435-1803
    URL: Article
    DOI: 10.1007/s00395-017-0646-x
    RVK:
    XA 31125
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1458470-0
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  • 5
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    Plasma AGE and Oxidation Products, Renal Function, and Preeclampsia in Pregnant Women with Type 1 Diabetes: A Prospective Observational Study
    Hindawi Limited ; 2023
    In:  Journal of Diabetes Research Vol. 2023 ( 2023-8-10), p. 1-10
    Details
    In: Journal of Diabetes Research, Hindawi Limited, Vol. 2023 ( 2023-8-10), p. 1-10
    Abstract: Aims. We aimed to determine whether plasma advanced glycation end products or oxidation products (AGE/oxidation-P) predict altered renal function and/or preeclampsia (PE) in pregnant women with type 1 diabetes. Methods. Prospectively, using a nested case-control design, we studied 47 pregnant women with type 1 diabetes, of whom 23 developed PE and 24 did not. Nineteen nondiabetic, normotensive pregnant women provided reference values. In plasma obtained at ~12, 22, and 32 weeks’ gestation (visits 1, 2, and 3; V1-V3), we measured five AGE products (carboxymethyllysine (CML), carboxyethyl-lysine (CEL), methylglyoxal-hydroimidazolone (MGH1), 3-deoxyglucosone hydroimidazolone (3DGH), and glyoxal-hydroimidazolone (GH1)) and four oxidation products (methionine sulfoxide (MetSO), 2-aminoadipic acid (2-AAA), 3-nitrotyrosine (3NT), and dityrosine (DT)), by liquid chromatography/mass spectroscopy. Clinical outcomes were “estimated glomerular filtration rate” (eGFR) at each visit and onset of PE. Results. In diabetic women, associations between AGE/oxidation-P and eGFR were found only in those who developed PE. In this group, CEL, MGH1, and GH1 at V2 and CML, CEL, MGH1, and GH1 at V3 were inversely associated with contemporaneous eGFR, while CEL, MGH1, 3DGH, and GH1 at V2 were inversely associated with eGFR at V3 (all p 〈 0.05 ). There were no associations of plasma AGE or oxidation-P with pregnancy-related development of proteinuria or PE. Conclusions. Inverse associations of second and early third trimester plasma AGE with eGFR among type 1 diabetic women who developed PE suggest that these patients constitute a subset susceptible to AGE-mediated injury and thus to cardiorenal complications later in life. However, AGE/oxidation-P did not predict PE in type 1 diabetic women.
    Type of Medium: Online Resource
    ISSN: 2314-6753 , 2314-6745
    URL: Article
    DOI: 10.1155/2023/8537693
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2023
    detail.hit.zdb_id: 2711897-6
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  • 6
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    198-LB: Maternal Plasma AGEs and Preeclampsia in Women with Type 1 Diabetes
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Preeclampsia (PE) occurs four times more frequently in pregnant women with type 1 diabetes (T1D) than in nondiabetic women. We hypothesized that elevated plasma advanced glycoxidation products (AGEs) predict PE in T1D women. In a prospective T1D pregnancy cohort (study visits at 12, 22, 32 weeks' gestation), we used liquid chromatography/mass spectrometry, with internal stable heavy isotope substituted standards, to determine plasma levels of nine AGE and oxidation products (carboxymethyl-lysine [CML] , carboxyethyl-lysine [CEL], methylglyoxal-hydroimidazolone [MGHI] , 3-deoxyglucosone hydroimidazolones [3DGH], methionine sulfoxide [MetSO] , glyoxal hydroimidazolone [GHI], 3-nitrotyrosine [3NT] , dityrosine [DT], 2-aminoadipic acid [2AAA] ) in 23 women with T1DM who developed PE vs. 24 who did not, and in 19 nondiabetic normotensive pregnant women. These products have been associated with CVD and renal failure in non-pregnant cohorts. All women were free of microalbuminuria and hypertension at enrolment, and all visits preceded clinical PE onset. GFR was estimated (Chronic Kidney Disease Epidemiology Collaboration equation). Results: Plasma CML, CEL, MGHI, 3DGH, MetSO, GHI, and 2AAA did not differ between the three groups at any study visit, and thus did not predict preeclampsia in T1D. In T1D women who later developed PE, eGFR was inversely associated at V3 with CML (p=0.008), CEL (p=0.03), MGH1 (p=0.03), 3DGH (p=0.03), GHI (p & lt;0.001), and 2AAA (p & lt;0.05); and at V2 with CEL (p=0.04), MGHI (p=0.02), and GHI (p=0.02). No such associations were observed in normotensive T1D or in nondiabetic pregnant women. Plasma levels of 3NT and DT were undetectable in all participants. Conclusions: Plasma AGEs did not predict PE in well-controlled, previously healthy T1D women, and levels did not differ from healthy nondiabetic controls. Uniquely, in T1D women who developed PE, plasma AGEs were associated with renal function, consistent with the notion that subclinical alterations in renal function precede PE. Disclosure H. Karanchi: None. C.B. Kelly: None. S.M. Hammad: None. R.L. Klein: None. M.F. Lopes-Virella: None. M.J. Leyva: None. J. Yu: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.J. Nankervis: None. K.F. Hanssen: None. C.E. Aston: None. S. Howell: Employee; Self; PreventAGE Health Care, LLC. P.J. Beisswenger: Other Relationship; Self; PreventAGE Health Care, LLC. T. Lyons: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-198-LB
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1501252-9
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  • 7
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    Methylglyoxal Can Modify GAPDH Activity and Structure
    Wiley ; 2005
    In:  Annals of the New York Academy of Sciences Vol. 1043, No. 1 ( 2005-06), p. 135-145
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1043, No. 1 ( 2005-06), p. 135-145
    Abstract: A bstract : The activity of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) can play an important role in regulating multiple upstream pathways relating to the development of diabetic complications. GAPDH can be modified by a number of metabolic factors, including oxidative and glycation products. To study the effect of glycation on GAPDH we have measured GAPDH structure and activity after exposure of the enzyme to the potent alpha dicarbonyl sugar methylglyoxal (MG). Rabbit GAPDH was incubated with 10‐1000 μM MG for 96 hours, and enzyme activity was measured at intervals by a spectrophotometric assay. Isoelectric focusing of purified and cellular GAPDH was performed with a PROTEAN IEF system and the bands visualized by Western blotting. The mass of glycated and native GAPDH was determined by MALDI with a Applied Biosystems Voyager System 6235. GAPDH activity (at 96 h) was decreased by 20% with 1.0 micromolar MG and showed progressively greater suppression of activity with increasing concentrations up to 1 mM, where activity was decreased by 97%. Reduction in GAPDH activity was rapidly decreasing by 69.2% by two hours with 1 mM MG. IEF showed an isoelectric point (IEP) of 8.5 for native GAPDH, while measurable changes were seen with modification by MG levels of 1 mM (IEP 7.5) and 50 μM (IEP 8.0). With MALDI, GAPDH mass increased from 36.012 kDa to 37.071 after exposure to 50 μM MG and to 40.625 following 1 mM MG. This indicates addition of 12.75 and 55.6 MG residues, respectively, to GAPDH. GAPDH can be modified by methylglyoxal intracellular concentrations close to those previously observed in vivo , with measurable changes in isoelectric point and mass. These modifications can lead to decreased enzyme activity, suggesting that conditions associated with elevated intracellular MG could modify GAPDH activity in vivo .
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Article
    DOI: 10.1196/annals.1333.017
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2005
    detail.hit.zdb_id: 2834079-6
    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
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  • 8
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    Formation of Immunochemical Advanced Glycosylation End Products Precedes and Correlates With Early Manifestations of Renal and Retinal Disease in Diabetes
    American Diabetes Association ; 1995
    In:  Diabetes Vol. 44, No. 7 ( 1995-07-01), p. 824-829
    Details
    In: Diabetes, American Diabetes Association, Vol. 44, No. 7 ( 1995-07-01), p. 824-829
    Abstract: Elevated levels of advanced glycosylation end products (AGEs) have been found in multiple tissues in association with diabetic vascular complications and during the microalbuminuric phase of diabetic nephropathy. In this study, we have used an AGE-specific enzyme-linked immunosorbent assay (ELISA) to measure skin AGEs to determine whether elevated levels can be detected before the onset of overt microangiopathy. Subjects with type I diabetes (n = 48) were graded for the degree of nephropathy (normal [23] , microalbuminuria [12], or macroalbuminuria [12] ) and retinopathy (none [13], background [20] , or proliferative [15]). Subgroups with a premicroalbuminuric phase of albumin excretion (≤28 mg/24 h, n = 27) or with the earliest stages of retinopathy (n = 27) were identified. A significant increase in tissue AGEs was found as urinary albumin increased during the premicroalbuminuric phase of nephropathy even when the data were adjusted for age and duration of diabetes (P = 0.005). Immunoreactive AGEs also increased as normal renal status advanced to microalbuminuria and macroalbuminuria (P = 0.0001 across groups). Significant elevation of AGEs was also found in association with the earliest stages of clinically evident retinopathy (early background versus minimal grades). In addition, higher AGE levels were found in subjects with proliferative retinopathy when compared with those with less severe retinopathy (P & lt; 0.004 across groups). In contrast, no significant differences were found in tissue AGE levels between groups with or without early retinopathy based on pentosidine or fluorescent AGE measurements, although fluorescent AGEs correlated with albumin excretion. In conclusion, levels of collagen-linked AGEs, when measured by an AGE-specific ELISA, reveal a correlation with preclinical stages of diabetic nephropathy and early retinopathy not indicated by other methods and may prove useful as early markers of microangiopathy in type I diabetes.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/diab.44.7.824
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1995
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  • 9
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    Quantitation of 3-Deoxyglucosone Levels in Human Plasma
    Elsevier BV ; 1997
    In:  Archives of Biochemistry and Biophysics Vol. 342, No. 2 ( 1997-06), p. 254-260
    Details
    In: Archives of Biochemistry and Biophysics, Elsevier BV, Vol. 342, No. 2 ( 1997-06), p. 254-260
    Type of Medium: Online Resource
    ISSN: 0003-9861
    URL: Article
    DOI: 10.1006/abbi.1997.0117
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1997
    detail.hit.zdb_id: 1461378-5
    SSG: 12
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  • 10
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    Plasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the American Heart Association Vol. 11, No. 15 ( 2022-08-02)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 15 ( 2022-08-02)
    Abstract: Advanced glycation endproducts (AGEs) have been linked to cardiovascular disease (CVD) in cohorts with and without diabetes. Data are lacking on prospective associations of various α‐dicarbonyl‐derived AGEs and incident CVD in the general population. We tested the hypothesis that major plasma AGEs are associated with new‐onset CVD in 2 population‐based cohorts of differing age and comorbidities. Methods and Results Analyses involved a random subcohort (n=466) from the Cardiovascular Health Study and a case‐cohort sample (n=1631) from the Multi‐Ethnic Study of Atherosclerosis. Five AGEs and 2 oxidative products were measured by liquid chromatography tandem mass spectrometry. Associations with CVD (myocardial infarction and stroke) were evaluated with Cox regression. Participants in the Cardiovascular Health Study were older than the Multi‐Ethnic Study of Atherosclerosis, and had more comorbidities, along with higher levels of all AGEs. During median follow‐up of 11 years, 439 participants in the Multi‐Ethnic Study of Atherosclerosis and 200 in the Cardiovascular Health Study developed CVD. After multivariable adjustment, carboxymethyl‐lysine, 3‐deoxyglucosone hydroimidazolones and a summary variable of all measured AGEs (principal component 1) were significantly associated with incident CVD in the Cardiovascular Health Study (HRs [95% CI]: 1.20 [1.01, 1.42] , 1.45 [1.23, 1.72], and 1.29 [1.06, 1.56] , respectively), but not the Multi‐Ethnic Study of Atherosclerosis. Oxidative products were not associated with CVD in either cohort. Conclusions We found α‐dicarbonyl‐derived AGEs to be associated with CVD in an older cohort, but not in a healthier middle‐aged/older cohort. Our results suggest that AGEs may exert detrimental cardiovascular effects only under conditions of marked dicarbonyl and oxidative stress. Further investigation of α‐dicarbonyl derivatives could lead to potential new strategies for CVD prevention in high‐risk older populations.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.121.024012
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2653953-6
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