1. MANAGEMENT OF OBESITY AND RELATED CONDITIONS: Does Diet Composition Matter? Lisa M. Neff, MD, MS Assistant Professor of Endocrinology Northwestern University Presented at Obesity 2010, San Diego, CA

3. Objectives To review the evidence regarding the effects of dietary macronutrient composition on weight loss outcomes. To review the evidence regarding the effects of diet composition on metabolic parameters in the absence of weight loss. the DASH diet the low glycemic index diet

4. DIETARY MACRONUTRIENT COMPOSITION AND WEIGHT LOSS

5. Expected mean body weight over time, by diet group Yancy W S et al. Ann Intern Med 2004;140:769-777 ©2004 by American College of Physicians Low fat -6.5 kg Low carb -12.0 kg

6. Dietary Macronutrient Composition and Weight Loss: Positive Studies StudynDurationMean Weight Change by Diet Shai I, NEJM, 2008 3222 yrLC - 4.7 kg Med - 4.4 kg LF - 2.9 kg Gardner CD, JAMA, 2007 3111 yrLC (Atkins) - 4.7 kg HP (Zone) -1.6 kg LF (Ornish) - 2.2 kg LF (LEARN) - 2.6 kg LC = low carb, Med = Mediterranean, LF = low fat, HP = high protein

7. Gardner, C. D. et al. JAMA 2007;297:969-977. Weight Change Relative to Baseline

8. Predicted absolute mean change in body weight for participants in the low-fat and low-carbohydrate diet groups, based on a random-effects linear model. Error bars represent 95% CIs. Foster G D et al. Ann Intern Med 2010;153:147-157 ©2010 by American College of Physicians

9. Dietary Macronutrient Composition and Weight Loss: Negative Studies StudynDurationMean Weight Change by Diet Foster GD, Ann Intern Med, 2010 3072 yrLC - 6.3 kg LF - 7.4 kg Sacks FM, NEJM, 2009 8112 yrLF/SP LF/HP HF/SP - 3.0 to - 3.6 kg HF/HP Brinkworth GD, AJCN, 2009 1071 yrLC -13.1 kg LF - 11.6 kg LC = low carb, LF = low fat, HF = high fat, SP = standard protein, HP = high protein

10. Dietary Macronutrient Composition and Weight Loss: Negative Studies StudynDurationMean Weight Change by Diet Frisch S, Cardiovasc Diabetol, 2009 2001 yrLC -5.8 kg LF -4.3 kg Layman DK, J Nutr, 2009 1301 yrHP - 9.3 kg LF - 7.4 kg Keogh JB, Br J Nutr, 2007 731 yrHM -7.6 kg HP - 4.8 kg LC = low carb, HP = high protein, LF = low fat, HM = high MUFA

11. Dietary Macronutrient Composition and Weight Loss: Negative Studies StudynDurationMean Weight Change by Diet Ebbeling CB, JAMA, 2007 7318 moLG = LF (~ - 2 kg) Das SK, AJCN, 2007 341 yrLG -7.8% LF – 8.0% Dansinger ML, JAMA, 2005 1601 yrLC (Atkins) - 2.1 kg HP (Zone) - 3.2 kg LF (Wt Watchers) - 3.0 kg LF (Ornish) -3.3 kg LG = low glycemic load, LC = low carb, HP = high protein, LF = low fat

12. Dietary Macronutrient Composition and Weight Loss: Negative Studies StudynDurationMean Weight Change by Diet Stern L, Ann Intern Med, 2004 1321 yrLC - 5.1 kg LF - 3.1 kg Due A, Int J Obes, 2004 501 yrHP/LF - 6.2 kg SP/LF - 4.3 kg Foster GD, NEJM 2003 631 yrLC - 4.4% LF - 2.5% HP = high protein, LF = low fat, SP = standard protein, LC = low carb

13. Dietary Macronutrient Composition and Body Composition Changes Positive Studies HP > LF Body fat: Layman DK et al., J Nutr, 2009 Abdominal fat, waist circ: Due A, Int J Obes, 2004 LC > LF Waist circ: Frisch S, Cardiovasc Diabetol, 2009 Negative Studies LC = LF Foster GD, Ann Intern Med, 2010 Brinkworth GD, AJCN 2009 HM = HP Keogh JB, Br J Nutr, 2007 LG = LF Ebbeling CB, JAMA, 2007 Das SK, AJCN, 2007 HP = high protein, LF = low fat, LC = low carb, HM = high MUFA, LG = low glycemic load

14. Individual percent weight changes at 2 year for 270 subjects completing the DIRECT intervention, comparing a low fat diet, a Mediterranean diet, and a low carb diet. From Greenberg I, J Am Coll Nutr, 2009

16. Dansinger, M. L. et al. JAMA 2005;293:43-53. One-Year Changes in Body Weight as a Function of Dietary Adherence Level Weight change, kg. 0 -5 +5+5 -10 -15 -20 -25 -30 +10 +15

17. Weight Loss Outcomes May Be Influenced by Metabolic Profile Ebbeling CB, JAMA, 2007 Subjects with high insulin secretion after an OGTT lost more weight (and more fat) on a low GL diet than on a standard LF diet. Those with low insulin secretion lost the same with a low GL or LF diet. Pittas A, Diabetes Care, 2005. Subjects with high insulin secretion after an OGTT lost more weight on a HP, low GL diet than on a high carb, high GL diet. Those with low insulin secretion tended to lose more weight with a high GL diet (NS). Cornier MA, Obes Res, 2005. Insulin sensitive women lost more weight with a LF diet, whereas insulin resistant women lost more weight with a HP diet.

18. However… Other studies suggest low fat, low carb, and low glycemic load diets are equally effective for long-term weight loss in patients with type 2 diabetes: Davis NJ, Diabetes Care, 2009 Wolever TM, AJCN, 2008 Brinkworth GD, Diabetologia, 2004

19. DIETARY COMPOSITION AND METABOLIC PARAMETERS IN THE ABSENCE OF WEIGHT LOSS

20. The DASH Diet High in fruits and vegetables (typically 10 servings/day or more), whole grains, and low fat dairy products(2-3 servings/day or more) Moderate amounts of nuts, beans, fish and poultry Limited red meat, fried foods, and sweets Low in cholesterol, saturated fat, sugars, and sodium High in calcium, magnesium, potassium, vitamins, phytochemicals, and fiber

21. The DASH Diet High in fruits and vegetables (typically 10 servings/day or more), whole grains, and low fat dairy products(2-3 servings/day or more) Moderate amounts of nuts, beans, fish and poultry Limited red meat, fried foods, and sweets Low in cholesterol, saturated fat, sugars, and sodium High in calcium, magnesium, potassium, vitamins, phytochemicals, and fiber

22. The DASH Diet At weight stability, the DASH diet: Lowers blood pressure in normotensive and hypertensive adults (Appel, NEJM 1997, Sacks, NEJM 2001) Reduces LDL cholesterol (Obarzanek, AJCN 2001) But, it may also: Reduce HDL cholesterol, like other low-fat diets (Obarzanek, AJCN, 2001) Increase TG in some patients, like other high carbohydrate diets (Erlinger, Circulation, 2003)

23. The DASH Diet Weight loss studies suggest the diet: May reduce fasting glucose and improve insulin sensitivity more than standard weight loss diets (Azadbakht, Diabetes Care 2005, Ard, Diabetes Care 2004) May reduce inflammatory markers such as C-reactive protein and increase levels of adiponectin (Lien, Obesity, 2006) May increase antioxidant capacity and reduce oxidative stress (Lopes, Hypertension, 2003 )

24. Ludwig, D. S. JAMA 2002;287:2414-2423. Foods with similar carbohydrate content can affect blood glucose levels differently Glycemic Index

25. Potato Instant oatmeal White bread Watermelon Basmati rice Stoneground whole wheat bread Raisins Pineapple Kidney beans Chocolate ice cream Oatmeal made with steel-cut oats Spaghetti, al dente

26. Low Glycemic Index Diets Without weight loss, low GI diets: Reduce postprandial glucose levels in normal individuals and people with diabetes (Ludwig, JAMA, 2002) Produce modest improvements in HbA1c in patients with diabetes (Thomas D, Cochrane Database Syst Rev, 2009) May or may not affect insulin sensitivity

27. Low Glycemic Index Diets Without weight loss, low GI diets may: increase HDL (Luscombe, EJCN, 1999) reduce inflammatory markers such as IL-1 β and IL-6 (Kallio, AJCN, 2008) increase antioxidant capacity (Botero, Obesity, 2009)

28. Low Glycemic Index Diets With weight loss: In overweight and obese adults (n=39), a low GI diet produced greater improvements in the following, as compared to a low fat diet (despite identical weight loss of 10%) : insulin resistance TG CRP blood pressure (Pereira MA, JAMA, 2004)

29. Summary Dietary macronutrient composition does not influence weight loss outcomes in the general population. Dietary adherence influences weight loss outcomes. Other factors (such as insulin resistance) might influence weight loss outcomes. Dietary micronutrient and macronutrient composition may influence metabolic parameters in the absence of weight loss.

30. Future Directions

31. Wt Stable on Western Diet Testing #1 Wt Stable on Western Diet Wt Stable on DASH Diet Wt Stable on Low GI Diet Testing #2 Subjects: n=39, ages 18-65, with insulin resistance and the metabolic syndrome. Outcomes: insulin sensitivity, glycemic control, lipids, blood pressure, inflammatory markers 2 weeks Inpatient 2 weeks Inpatient