Dean Pomerleau Posted August 25, 2016 Report Share Posted August 25, 2016 Here is an useful new study  (press release) for folks concerned about risk of impaired glucose tolerance, insulin insensitivity, and diabetes. It was a one-year randomized control trial of obese folks with metabolic syndrome, but not overt diabetes. Half the participants (the Reg-AGE group) ate their normal diet and used their normal cooking methods for the year. The other half (the Low AGE or L-AGE group) were told not to change what or how much they ate, but simply to use cooking techniques known to minimize the formation of Advanced Glycation End-products (AGEs). In particular, they were instructed as follows: L-AGE participants prepared their own food at home after being individually instructed on how to reduce dietary AGE intake by modifying the cooking time and temperature without changing the quantity, quality or composition of food. They were specifically instructed to avoid frying, baking or grilling, and they were encouraged to prepare their food by boiling, poaching, stewing or steaming. Below is a sample daily diet for both the Reg-AGE and the L-AGE diets. Note these are just examples given to the L-AGE subjects for how to model their own, self-selected low AGE diet. They were given phone calls twice per week from a dietitian to encourage and facilitate compliance: Based on diet questionnaire responses, compliance was good. The AGE intake was about 65% lower in the L-AGE group compared with the Reg-AGE group by the end of the study. Both groups lost a modest, nearly comparable amount of weight (1-3 lbs on average) - not enough to explain the following differences. Here are the dramatic main results, in graphical form (black bars represent the L-AGE group and the white bars represent the Reg-AGE group): As you can see from the first graph, insulin sensitivity (HOMA-IR - a measure of pancreatic β-cell function) improved, and fasting leptin and insulin dropped on the L-AGE diet. While glucose area-under-the-curve in response to an OGTT didn't improve, the second graph shows that the L-AGE group used dramatically less insulin to clear the same amount of glucose, indicating that their insulin sensitivity was much improved. The third graph shows that important markers of circulating AGEs and markers of systemic inflammation (e.g. TNFα) came down dramatically in the L-AGErs, but rose across the board in the Reg-AGE group. The opposite was true for pro-health and longevity markers like the level of SIRT1 and adiponectin - which went up in L-AGE folks by the end of the study, and stayed flat or dropped in the Reg-AGE group. The authors conclude the paper with: L-AGE [diet] is effective against insulin resistance in obese individuals with the metabolic syndrome. Here is more good color commentary by the authors from the popular press interview (my emphasis): The investigators believe that daily AGE consumption in the standard Western diet is at least three times higher than the safety limit for these oxidants. This could, in part, explain the changes seen in disease demographics. Dr. Vlassara cautioned, "Even though the AGEs pose a more immediate health threat to older adults, they are a similar danger for younger people, including pregnant women and children, and this needs to be addressed. AGEs are ubiquitous and addictive, since they provide flavor to foods. But they can be controlled through simple methods of cooking, such as keeping the heat down and the water content up in food and by avoiding pre-packaged and fast foods when possible. Doing so reduces AGE levels in the blood and helps the body restore its own defenses." Sorry to rain on your Labor Day cookouts, but you, your family and friends may want to skip the barbie (not to mention the fry pan, oven and toaster) to reduce your risk of impair glucose metabolism, insulin resistance, not to mention cancer . --Dean ----------  Diabetologia. 2016 Jul 29. [Epub ahead of print] Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial. Vlassara H(1,)(2), Cai W(1), Tripp E(1), Pyzik R(1), Yee K(1), Goldberg L(1), Tansman L(1), Chen X(1), Mani V(3), Fayad ZA(3), Nadkarni GN(4), Striker GE(1,)(4), He JC(4), Uribarri J(5). 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). DOI: 10.1007/s00125-016-4053-x PMID: 27468708 ------  Diabetes Metab Syndr Obes. 2015 Sep 1;8:415-26. doi: 10.2147/DMSO.S63089. eCollection 2015. Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management. Palimeri S(1), Palioura E(1), Diamanti-Kandarakis E(1). Author information: (1)Endocrine Unit, Medical School University of Athens, Athens, Greece. Advanced glycation end products (AGEs) constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxins). Modern Western diets are rich in AGEs which have been implicated in the pathogenesis of several metabolic and degenerative disorders. Accumulating evidence underlies the beneficial effect of the dietary restriction of AGEs not only in animal studies but also in patients with diabetic complications and metabolic diseases. This article reviews the evidence linking dietary glycotoxins to several disorders from diabetic complications and renal failure to liver dysfunction, female reproduction, eye and cognitive disorders as well as cancer. Furthermore, strategies for AGE reduction are discussed with a focus on dietary modification. DOI: 10.2147/DMSO.S63089 PMCID: PMC4562717 PMID: 26366100 Link to comment Share on other sites More sharing options...
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