Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial

Abstract

Aims/hypothesis 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. Methods 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. Results 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. Conclusions/interpretation 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. Trial registration ClinicalTrials.gov NCT01363141 Funding The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK091231)

Increased odds of metabolic syndrome with consumption of high dietary advanced glycation end products in adolescents

“…A recent randomized controlled trial has shown improvement in metabolic parameters in participants randomized to a low AGE diet. 7 Temperature and methods of cooking seem to be more critical to AGE formation than cooking time. 8 Habitual preference of foods such as full-fat cheeses, meats, and highly processed foods in excess results in increased dAGE consumption, and therefore increasing the intake of fish, grains, low-fat milk products, fruits, and vegetables reduces consumption of dAGEs.…”

Consumption of diets with low advanced glycation end products improves cardiometabolic parameters: meta-analysis of randomised controlled trials

“…It was not possible to conduct meta-analysis for glucose area under the curve (AUC) as there was only one study that reported on this measure 23 .…”

Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

“…First, the high-temperature and long-time cooking of foods can generate AGEs that are exogenously introduced with the diet [46]. Second, emerging evidence indicates that high dietary simple sugars consumption can represent a substantial source of endogenous AGEs [47].…”

“…Though, also the reduction of dietary (exogenous) AGEs in type 2 diabetes or obese patients, without modification of the total calories intake, has been demonstrated to be effective in amelioration of insulin sensitivity, with reduction of inflammatory markers and restoration of AGEs detoxifying systems and mitochondrial metabolism regulators [46,93]. Similarly, endogenous and exogenous AGEs have been related to cognitive decline and impaired memory in two different studies indicating that serum levels of methylglyoxal in elderly individuals were directly correlated with dietary AGEs intake and cognitive decline assessed by the Mini Mental State Examination [94,95].…”