1. CONSUMPTION OF A DIET LOW IN ADVANCED GLYCATION END PRODUCTS FOR 4 WEEKS IMPROVES INSULIN SENSITIVITY IN OVERWEIGHT WOMEN GABBY SHERER DIABETES SELF MANAGEMENT EDUCATION MARY JULIUS RD, CDE, LD NEAL KURMAS MS, RD, CDE, LD

2. CITATION Budek-Mark A, Poulsen M, Andersen S, et al. Consumption of a Diet Low in Advanced Glycation End Products for 4 Weeks Improves Insulin Sensitivity in Overweight Women. Diabetes Care. 2014; 37: 88-95.

3. ADVANCED GLYCATION END PRODUCTS (AGES) Glycation: addition of a CHO to a Protein without an enzyme Formed endogenously: In DM d/t increased carbonyl stress Formed exogenously: Maillard Reaction  btw amino acids and reducing sugars  browning All tissues glycate, examples: RBC - HgbA1C Albumin- fructosimine measured in pregnancy d/t short half life Collagen- Skin Autofluorescence RAGE on endothelial, smooth muscle, and immune system cells leads to chronic inflammatory diseases when binding AGEs.

4. BACKGROUND STUDIES Extracts of AGEs induce oxidative stress in vitro Animals consuming diet high in AGEs show increased insulin levels, insulin resistance, and T2DM AGE restricted diet beneficial to glucose metabolism in T2DM pts

5. OBJECTIVE Compare the effects of high AGE and low AGE diets along with fructose or glucose supplements on insulin sensitivity in overweight, but otherwise healthy women.

6. DESIGN 4 week- randomized Low AGE 37 74 Fruct High AGE 37 Gluc Open Double blind

7. N=74 Women Age 20-50 years BMI 25-40 kg/m 2 Waist circumference >88 cm Copenhagen, Denmark Department of Nutrition, Exercise, and Sports at U of Copenhagen 2012 Exclusion: Wt change >3 kg in 2 mo Physical Activity >8h/week Current smoking Use of dietary supplements or medications Known medical condition Vegetarianism Pregnant/breastfeeding Surgery to treat obesity Menopausal Blood donation in last 3 mo Hypersensitivity to PABA PARTICIPANTS AND SETTING

8. INTERVENTION At baseline and after 4 weeks: Fasting blood draws (abstain from alcohol and vigorous exercise x 48h) Urine collection – 3 X 80 mg PABA for compliance Anthropometrics OGTT AF Phone calls at halfway point for compliance

9. INTERVENTION Both diets consisted of Danish Cuisine and similar in nutrient content Oral and written instruction provided  Cooking methods  Food choice list  Recipes for mandatory meals Weighed food records for first 3 and last 3 days of intervention

10. DIETS HIGH AGE Fry, bake, roast, or grill foods Eat toasted bread with crust Follow food choice list Examples: Fried eggs Muesli Tortilla chips biscuits LOW AGE Boil or steam foods Eat bread without a crust Follow food choice list Examples: Boiled eggs Oatmeal Rice cakes muffins

12. INTERVENTION Participants provided 84 bottles monosaccharide  20g fructose monohydrate powder  22g glucose monohydrate powder Consume 3 sugar supplements, dissolved in water, with meals daily Added sugar and sugar containing foods prohibited – other than provided snacks

13. MAIN OUTCOME MEASURES PRIMARY HOMA-IR SECONDARY Glucose Insulin Glucagon-like peptide-1 (GLP-1) Lipid profile Insulin sensitivity index Weight BMI Waist circumference Waist to hip ratio Skin autofluorescence Urinary excretion of AGEs (CML and MG-H1)

14. STATISTICAL ANALYSIS Power: of 0.80 with a 30% change in HOMA IR  88 participants Primary and Secondary outcomes  Two-way ANOVA  With covariates to adjust for baseline levels, age and changes in weight and waist circumference from baseline Interaction and main effects  Means of F test Baseline values of anthropometric and metabolic variables  Two sample T-tests Associations btw urinary AGEs and metabolic variables  Means of Pearson correlation coefficients

15. Urinary excretion (mean ± SEM) of CML (A) and MG-H1 (B) in milligrams per 24 h in high-AGE (black bars, n = 37) and low-AGE (white bars, n = 36) groups at baseline and after 4 weeks of dietary intervention. Mark A B et al. Dia Care 2014;37:88-95 Copyright © 2011 American Diabetes Association, Inc.

17. RESULTS Significant decrease in wt, BMI, and waist circumference in both groups, but more in the low AGE group (similar at baseline)

18. CONCLUSIONS Low AGE diet Improves insulin resistance in overweight women. Weaknesses: Did not reach statistical power OGTT at 0 and 120 min only Change in anthropometrics Differing diet composition Not generalizable to men

19. CLINICAL IMPLICATIONS Avoid fried foods Avoid highly processed foods Eat more fresh fruits and Vegetables Low AGEs beneficial in those with DM and in prevention of DM