Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links

Groener, Jan B.; Oikonomou, Dimitrios; Cheko, Ruan; Κender, Ζoltan; Zemva, Johanna; Kihm, Lars; Muckenthaler, Martina U.; Peters, Verena; Fleming, Thomas; Kopf, Stefan; Nawroth, Peter P.

doi:10.1055/s-0043-106443

Cited by 47 publications

(45 citation statements)

References 69 publications

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“…Protein-bound and free AGEs have been shown to be significantly elevated in experimental models of diabetes and in diabetic patients [6], [7], [8], [9], in parallel with their precursors [10], [11]. Studies have also shown that there is an association between AGEs and diabetic micro- and macrovascular complications (Reviewed in [12]), an association which is independent of HbA 1c . The reasons for this discrepancy may be due to the loss of detoxification capacity.…”

Section: Introductionmentioning

confidence: 99%

Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes

Schumacher

Morgenstern

Oguchi

et al. 2018

Molecular Metabolism

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ObjectivesThe deficit of Glyoxalase I (Glo1) and the subsequent increase in methylglyoxal (MG) has been reported to be one the five mechanisms by which hyperglycemia causes diabetic late complications. Aldo-keto reductases (AKR) have been shown to metabolize MG; however, the relative contribution of this superfamily to the detoxification of MG in vivo, particularly within the diabetic state, remains unknown.MethodsCRISPR/Cas9-mediated genome editing was used to generate a Glo1 knock-out (Glo1−/−) mouse line. Streptozotocin was then applied to investigate metabolic changes under hyperglycemic conditions.ResultsGlo1−/− mice were viable and showed no elevated MG or MG-H1 levels under hyperglycemic conditions. It was subsequently found that the enzymatic efficiency of various oxidoreductases in the liver and kidney towards MG were increased in the Glo1−/− mice. The functional relevance of this was supported by the altered distribution of alternative detoxification products. Furthermore, it was shown that MG-dependent AKR activity is a potentially clinical relevant pathway in human patients suffering from diabetes.ConclusionsThese data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG.

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Section: Introductionmentioning

confidence: 99%

Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes

Schumacher

Morgenstern

Oguchi

et al. 2018

Molecular Metabolism

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“…A késői glikációs végtermékek -elsősorban az oxidatív stressz fokozódása révén -nagyban hozzájárulnak az érelmeszesedéshez és ezáltal a macrovascularis szövődmények kialakulásához [44]. Ezen túlmenően az AGE termékek kiemelkedő jelentőséggel bírnak a microvascularis szövődmények patomechanizmusában [45,46], amelyek közül a diabeteses nephropathiának szintén szerepet tulajdonítanak a szív-és érrendszeri betegségek kialakulásában [47]. A metforminkezelés igazoltan csökkenti mind a reaktív metabolitok, mind a következményes AGE termékek képződését [48][49][50].…”

Section: Megbeszélésunclassified

A metformin hatása a vérzsírértékekre, illetve a szív és érrendszeri kockázatra sztatinkezelésben nem részesülő 2-es típusú cukorbetegekben

et al. 2019

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Introduction: Some meta-analyses suggested a positive effect of metformin therapy on lipid parameters, but the potential beneficial effect of metformin on cardiovascular risk in type 2 diabetes is not entirely clear. Aim: We investigated the effect of metformin therapy on lipid parameters and cardiovascular risk in patients with type 2 diabetes. Method: In a cross-sectional, monocentric study, 102 patients with type 2 diabetes without lipid-lowering medication were analysed for lipid profile and cardiovascular risk (United Kingdom Prospective Diabetes Study Risk Calculator) depending on metformin therapy. The patients were divided into two subgroups regarding with (n = 52) or without metformin therapy (n = 50). Results: Patients with metformin therapy had significantly lower total cholesterol and LDL cholesterol levels than patients without metformin (p<0.01 and p<0.05). This effect was independent from glucose control. No intrinsic effect of metformin could be found on systolic blood pressure, HDL cholesterol, triglycerides, and long-term cardiovascular risk using a multivariable risk assessment score. Conclusion: Metformin therapy has beneficial effects on cholesterol levels without improving cardiovascular risk in patients with type 2 diabetes. Orv Hetil. 2019; 160(34): 1346–1352.

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“…In den aktuellen Hypothesen geht man ebenfalls von oxidativem Stress, erhöhter ROS-Produktion und inflammatorischer Hyperaktivierung aus. Diese werden vor allem durch reaktive Metabolite, Advanced Glycation Endproducts (AGE) und gestörte Fettsäureoxidation hervorgerufen [27][28][29]. Diese Mechanismen verursachen ähnlich wie bei der Lungenfibrose vaskuläre Mikroläsionen, die über Endotheldysfunktionen und Apoptose zu Gerinnungsaktivierung, Chemokinfreisetzung und Kollagensynthese führen [28].…”

Section: Epidemiologie Und Pathophysiologieunclassified

Diabetische Pneumopathie

Kopf¹

2019

Diabetologie und Stoffwechsel

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Breathlessness or dyspnea is a frequent symptom in patients with diabetes and the first disease which has to be excluded is the coronary heart disease. However, previous epidemiological studies have shown that patients with diabetes mellitus have an increased risk for fibrotic pulmonary diseases, such as the idiopathic pulmonary fibrosis (IPF). Recent studies were able to show that patients with newly diagnosed type 2 diabetes have impaired pulmonary oxygen consumption and over 26 % of patients with long-term type 2 diabetes showed restrictive lung function with fibrotic interstitial lung diseases. Especially patients with type 2 diabetes and nephropathy had an 8-fold higher risk for lung diseases. This is not surprising since the pathomechanisms of pulmonary fibrosis and diabetic complications have much in common: reactive oxygen species induce DNA-damage with consecutive activation of inflammatory cytokines which induce fibrotic remodeling of the tissue. This leads us to the suggestion that patients with diabetes, albuminuria and breathlessness should be examined for interstitial lung disease on regular basis. However, data regarding the natural course of diabetic pneumopathy and therapeutic approaches are still missing. Small intervention studies with IPF-patients could show that sports and physical activity were able to stabilize the disease progression.

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Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links

Cited by 47 publications

References 69 publications

Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes

Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes

A metformin hatása a vérzsírértékekre, illetve a szív és érrendszeri kockázatra sztatinkezelésben nem részesülő 2-es típusú cukorbetegekben

Diabetische Pneumopathie

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