Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects

Forbes, Josephine M.; Sourris, Karly C.; Courten, Maximilian Pangratius J De; Dougherty, Sonia L; Chand, Vibhasha; Lyons, Jasmine G.; Bertovic, David A.; Coughlan, Melinda T.; Schlaich, Markus P.; Soldatos, Georgia; Cooper, Mark E.; Straznicky, Nora E.; Kingwell, Bronwyn A.; Courten, Barbora de

doi:10.1007/s00726-013-1542-9

Cited by 30 publications

(23 citation statements)

References 39 publications

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“…In support of our findings that lower serum CML is associated with greater insulin resistance, obese humans with evidence of very early metabolic dysfunction and insulin resistance also have lower circulating serum protein-bound AGE concentrations such as CML (6,23,24). The significance of this decrease in protein-bound CML before overt hyperglycemia remains to be determined.…”

Section: Discussionsupporting

confidence: 68%

Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial

Courten

Soldatos

et al. 2016

The American Journal of Clinical Nutrition

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Background: The consumption of advanced glycation end products (AGEs) has increased because of modern food processing and has been linked to the development of type 2 diabetes in rodents. Objective: We determined whether changing dietary AGE intake could modulate insulin sensitivity and secretion in healthy, overweight individuals. Design: We performed a double-blind, randomized, crossover trial of diets in 20 participants [6 women and 14 men; mean 6 SD body mass index (in kg/m 2 ): 29.8 6 3.7]. Isoenergetic-and macronutrientmatched diets that were high or low in AGE content were alternately consumed for 2 wk and separated by a 4-wk washout period. At the beginning and end of each dietary period, a hyperinsulinemiceuglycemic clamp and an intravenous glucose tolerance test were performed. Dietary, plasma and urinary AGEs N V -(carboxymethyl) lysine (CML), N V -(carboxyethyl)lysin (CEL), and methylglyoxalderived hydroimadazolidine (MG-H1) were measured with the use of mass spectrometry. Results: Participants consumed less CML, CEL, and MG-H1 during the low-AGE dietary period than during the high-AGE period (all P , 0.05), which was confirmed by changes in urinary AGE excretion. There was an overall difference in insulin sensitivity of 22.1 mg $ kg 21 $ min 21 between diets (P = 0.001). Insulin sensitivity increased by 1.3 mg $ kg 21 $ min 21 after the low-AGE diet (P = 0.004), whereas it showed a tendency to decrease by 0.8 mg $ kg 21 $ min 21 after the high-AGE diet (P = 0.086). There was no difference in body weight or insulin secretion between diets (P = NS). Conclusions: A diet that is low in AGEs may reduce the risk of type 2 diabetes by increasing insulin sensitivity. Hence, a restriction in dietary AGE content may be an effective strategy to decrease diabetes and cardiovascular disease risks in overweight individuals. This trial was registered at clinicaltrials.gov as NCT00422253.

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Section: Discussionsupporting

confidence: 68%

Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial

Courten

Soldatos

et al. 2016

The American Journal of Clinical Nutrition

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112

104

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“…An animal study demonstrated that exposure to excess AGEs activates pathways of β -cell damage which, via mitochondrial superoxide generation, can impair insulin secretion [4]. A human study also showed a cross-sectional association between AGEs and acute insulin secretion during glucose tolerance testing in healthy humans [5]. Another human study demonstrated that the circulating level of AGEs is associated with insulin resistance as evaluated by the homeostasis model assessment for insulin resistance (HOMA-IR), even in nonobese, nondiabetic subjects [6].…”

Section: Introductionmentioning

confidence: 99%

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Okura

Ueta

Nakamura

et al. 2017

Journal of Diabetes Research

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Objective Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes.

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“…Ivancovsky‐Wajcman et al have suggested that serum sRAGE levels are associated with NAFLD that may function as a protective factor against RAGE in the AGEs‐RAGE/sRAGE system. Moreover, previous studies showed that CML accumulates much more pronounced in human fatty livers, where it is decomposed and secreted into the bloodstream as an unstable component. However, the association of circulating CML in serum with NAFLD is not known.…”

Section: Discussionmentioning

confidence: 99%

Middle‐ and high‐molecular weight adiponectin levels in relation to nonalcoholic fatty liver disease

Lian

Feng

et al. 2019

Clinical Laboratory Analysis

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Objective: Adiponectin (APN) circulates as high-molecular weight (HMW), mediummolecular weight (MMW), and low-molecular weight (LMW) forms. Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Currently, the role of LMW, MMW, and HMW APN remains largely unclear in NAFLD. Methods:We examined the variation of these forms and analyzed the related clinical characteristics in NAFLD. A total of 63 male NAFLD patients (mean age: 43.00 ± 6.10 years) and 70 healthy male subjects (mean age: 42.53 ± 7.98 years) were included in the study.Total APN and other clinical characteristics were measured. The changes in HMW, MMW, and LMW APN were determined in NAFLD patients and NAFLD patients on a high-fat diet, and the association between the groups was further analyzed.Results: Decreased levels of total APN and three APN isoforms were found in NAFLD. Significantly decreased levels of HMW (P < .01) and MMW (P < .001) were observed in NAFLD of high-fat diet patients. In NAFLD patients, height (R = −.270, P = .032) and N-epsilon-(carboxymethyl) lysine (R = −.259, P = .040) significantly correlated with total APN. HMW APN was significantly associated with fasting plasma glucose (R = .350, P = .016), alanine aminotransferase (R = −.321, P = .029), and aspartate aminotransferase (R = −.295, P = .045). Additionally, MMW APN was significantly associated with total cholesterol (R = .357, P = .014) and high-density lipoprotein (R = .556, P < .0001). Low-density lipoprotein (R = −.283, P = .054) was also clearly associated with LMW APN in NAFLD patients. Conclusion: These results suggest that HMW and MMW APN may be involved in the pathogenesis and progression of NAFLD. K E Y W O R D S adiponectin, high-molecular weight, low-molecular weight, middle-molecular weight, nonalcoholic fatty liver disease

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Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects

Cited by 30 publications

References 39 publications

Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial

Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Middle‐ and high‐molecular weight adiponectin levels in relation to nonalcoholic fatty liver disease

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