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Diet Low in AGE's Ameliorates Insulin Resistance - RCT

Gert van der Hoek

In Memoriam - Editor, Senior Moderator
Diabetologia. 2016 Jul 29. [Epub ahead of print]

[h=1]Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial.[/h]
[h=3]Abstract[/h]
[h=4]AIMS/HYPOTHESIS:[/h] We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome.
[h=4]METHODS:[/h] A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome.
[h=4]RESULTS:[/h] Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements. No side effects from the intervention were identified. HOMA-IR came down from 3.1 ? 1.8 to 1.9 ? 1.3 (p < 0.001) in the L-AGE group, while it increased from 2.9 ? 1.2 to 3.6 ? 1.7 (p < 0.002) in the Reg-AGE group.
[h=4]CONCLUSIONS/INTERPRETATION:[/h] L-AGE ameliorates insulin resistance in obese people with the metabolic syndrome, and may reduce the risk of type 2 diabetes, without necessitating a major reduction in adiposity. Elevated serum AGEs may be used to diagnose and treat 'at-risk' obesity.

 
[h=1]Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet[/h] J Am Diet Assoc. 2010 Jun; 110(6): 911?16.e12.
doi: 10.1016/j.jada.2010.03.018


[h=2]Abstract[/h] [FONT=&quot] Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease.

This report significantly expands the available dAGE database, validates the dAGE testing methodology, compares cooking procedures and inhibitory agents on new dAGE formation, and introduces practical approaches for reducing dAGE consumption in daily life. Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking.

The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar. The new dAGE database provides a valuable instrument for estimating dAGE intake and for guiding food choices to reduce dAGE intake.

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