Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease and Mortality in Individuals With Type 2 Diabetes

Hanssen, Nordin M.J.; Westerink, Jan; Scheijen, Jean L.J.M.; Graaf, Yolanda van der; Stehouwer, Coen D. A.; Schalkwijk, Casper G.

doi:10.2337/dc18-0159

Cited by 73 publications

(79 citation statements)

References 29 publications

(38 reference statements)

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“…Plasma levels of MGO are associated with the prevalence of CKD in diabetes [152][153][154]. Higher plasma MGO levels are associated with an increased risk for lower eGFR and increased albuminuria in both T1D and T2D [155][156][157]. In addition to impaired detoxification, low eGFR may contribute to higher plasma concentrations of MGO in patients with diabetic nephropathy because of metabolic stress in tissues which may enhance the formation of MGO and/or inhibit its metabolism [158].…”

Section: Dicarbonyl Synthesismentioning

confidence: 99%

Glucose and Blood Pressure-Dependent Pathways–The Progression of Diabetic Kidney Disease

Patel

Bose

Cooper

2020

IJMS

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The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such as methylglyoxal which activate intracellular pathways to promote fibrosis and inflammation in the kidney. Recent studies have identified a novel molecular interaction between hemodynamic and metabolic pathways which could lead to new treatments for DKD. This should lead to a further improvement in the outlook of DKD building on positive results from RAAS blockade and more recently newer classes of glucose-lowering agents such as SGLT2 inhibitors and GLP1 receptor agonists.

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Section: Dicarbonyl Synthesismentioning

confidence: 99%

Glucose and Blood Pressure-Dependent Pathways–The Progression of Diabetic Kidney Disease

Patel

Bose

Cooper

2020

IJMS

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“…31 Another related alpha-oxoaldehyde, methylglyoxal, was also found to be associated with incident cardiovascular disease and mortality in prospective studies of 1,003 type 2 and 159 type 1 diabetic patients. 32,33 Baseline and six-year longitudinal methylglyoxal levels were inversely correlated eGFR in 1481 screen-detected type 2 diabetic patients. 34 In a prospective three-year observational study of 150 individuals with CKD stages 3-5, higher methylgloxal levels (tertiles 2 and 3 compared with tertile 1) were associated with a >2-fold and > 6-fold increased risk for progression to ESRD, respectively.…”

Section: Diabetes Mellitus and Urinary Oxalate Excretionmentioning

confidence: 99%

Urinary oxalate as a potential mediator of kidney disease in diabetes mellitus and obesity

Efe

Verma

Waikar

2019

Current Opinion in Nephrology and Hypertension

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Purpose of review: Hyperoxaluria can cause kidney disease through multiple mechanisms, including tubular obstruction from calcium oxalate crystals, sterile inflammation, and tubular epithelial cell injury. Hyperoxaluria is also observed in individuals with diabetes mellitus and obesity, which are in turn risk factors for chronic kidney disease. Whether hyperoxaluria is a potential mediator of increased risk of chronic kidney disease in diabetes mellitus and obesity is unknown. Recent Findings: Individuals with diabetes have increased levels of plasma glyoxal (a protein glycation product) and glyoxylate, both of which are precursors for oxalate. Increased gut absorption of oxalate in obesity may be due to obesity-associated inflammation. A recent study in individuals with chronic kidney disease found that higher 24h urinary oxalate excretion was independently associated with increased risk of kidney disease progression, especially in individuals with diabetes and obesity. Summary: Both diabetes mellitus and obesity are associated with higher urinary oxalate excretion through distinct mechanisms. Hyperoxaluria could be a mechanism by which kidney disease develops in individuals with diabetes mellitus or obesity and could also contribute to progressive loss of renal function. Future research on pharmacologic or dietary measures to limit oxalate absorption or generation are required to test whether lowering urinary oxalate excretion is beneficial in preventing kidney disease development and progression in diabetes mellitus and obesity.

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“…The accumulation of advanced glycation end products (AGEs) is associated with accelerated aging [ 1 ] and may be involved in the development of degenerative disease––such as diabetes, cardiovascular disease and Alzheimer’s disease––by promoting insulin resistance, inflammation and oxidative stress [ 2 , 3 , 4 , 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Dietary Patterns on Advanced Glycation end Products: A Randomized Crossover Study

et al. 2020

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Dietary advanced glycation end products (AGEs) are believed to contribute to pathogenesis of diabetes and cardiovascular disease. The objective of this study was to determine if a diet high in red and processed meat and refined grains (HMD) would elevate plasma concentrations of protein-bound AGEs compared with an energy-matched diet high in whole grain, dairy, nuts and legumes (HWD). We conducted a randomized crossover trial with two 4-week weight-stable dietary interventions in 51 participants without type 2 diabetes (15 men and 36 women aged 35.1 ± 15.6 y; body mass index (BMI), 27.7 ± 6.9 kg/m2). Plasma concentrations of protein-bound Nε-(carboxymethyl) lysine (CML), Nε-(1-carboxyethyl) lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The HMD significantly increased plasma concentrations (nmol/mL) of CEL (1.367, 0.78 vs. 1.096, 0.65; p < 0.01; n = 48) compared with the HWD. No differences in CML and MG-H1 between HMD and HWD were observed. HMD increased plasma CEL concentrations compared with HWD in individuals without type 2 diabetes.

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Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease and Mortality in Individuals With Type 2 Diabetes

Abstract: Plasma MGO and GO levels are associated with cardiovascular mortality in individuals with type 2 diabetes. Influencing dicaronyl levels may therefore be a target to reduce CVD in type 2 diabetes.

Cited by 73 publications

References 29 publications

Glucose and Blood Pressure-Dependent Pathways–The Progression of Diabetic Kidney Disease

Glucose and Blood Pressure-Dependent Pathways–The Progression of Diabetic Kidney Disease

Urinary oxalate as a potential mediator of kidney disease in diabetes mellitus and obesity

Differential Effects of Dietary Patterns on Advanced Glycation end Products: A Randomized Crossover Study

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