BackgroundAdvanced glycation end products (AGEs) are formed during the processing, storage, and cooking of foods. As part of a western diet, AGEs are consumed in excess and impair glucose metabolism in patients with type 2 diabetes. In the absence of diabetes, AGE-mediated decreases in insulin sensitivity and signaling have been postulated. However, randomized studies to test this relationship in humans are limited.ObjectiveThe primary aim of this trial is to determine whether dietary consumption of AGEs will decrease insulin sensitivity in healthy overweight adults. A secondary aim is to determine the effects of dietary AGEs on insulin secretion, circulating soluble receptor for AGEs (sRAGE), and inflammation markers.MethodsOverweight, but otherwise healthy, non-diabetic adults (N=20) aged 18-50 years old will complete a randomized cross-over design intervention study alternating low and high (4-fold increase) AGE diets (2-week duration). At baseline, participants will undergo a medical review including an intravenous glucose tolerance test (IVGTT), a hyperinsulinemic-euglycemic clamp, and anthropometric measures and questionnaires assessing diet, physical activity, and general wellness. Each test diet will be followed for 14 days, followed by a 4-week washout period before commencement of the second alternate dietary period. Energy, macronutrient, and AGE intake will be calculated for each dietary period. Additionally, the AGE content of foods used in the study will be measured by ultra performance liquid chromatography mass spectrometry. All measurements will be repeated at the beginning and end of each dietary period. Primary and secondary outcomes will be expressed as a change over the dietary period for insulin sensitivity, secretion, anthropometric parameters, sRAGE, and inflammation markers and compared by paired t test and analysis of variance (ANOVA).ResultsThe study will be completed in early 2016.ConclusionThe proposed trial will provide much needed clinical evidence on the impact of excess dietary AGE consumption on insulin sensitivity and will indicate whether lowering dietary AGE intake can improve insulin sensitivity and/or secretion, thereby decreasing risk for type 2 diabetes.Trial RegistrationClinicaltrials.gov NCT00422253; https://clinicaltrials.gov/ct2/show/NCT00422253 (Archived by Webcite at http://www.webcitation.org/6ZXLhT89c)
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