The Reduced Obese State: The Challenge of Weight Maintenance 2011 Annual CAN Conference November 17, 2011

Transcription

1 The Reduced Obese State: The Challenge of Weight Maintenance 2011 Annual CAN Conference November 17, 2011 Robert H. Eckel, M.D. Professor of Medicine Professor of Physiology and Biophysics Charles A. Boettcher II Chair in Atherosclerosis University of Colorado Anschutz Medical Campus

2 Duality of Interests Advisory Boards Amylin Esperion Genentech Genfit GTC Nutrition Johnson & Johnson Lilly Merck Pfizer Regulus sanofi-aventis Grants/Research Fellowships Diadexus GSK sanofi-aventis Educational Venues AccelMed Cardiometabolic Health Congress Vindico VoxMed

3 Prevention of Weight Gain It s all a matter of energy balance! In the absence of edematous disorders, if you re burning less than you re eating you gain weight E Out < E In WT And it s much less than the 100 kcal/day estimated by Hill JO et al (Science, 2003)

4 Obesity Incidence Based on Energy Balance Calculations BMI 25.0 kg/m 2, Ht - 68, Wt 164 lb vs. BMI 30.0 kg/m 2, Ht 68, Wt 197 lb over 20 years is 13 kcal/day excess

5 Body Weight Regulation SET OR SETTLING POINT?

6 Schematic Representation of the Natural History of Obesity Body Weight prevention therapeutic space years months years Time Eckel RH, Kahn S et al: Diabetes Care 34:1424 and JCEM 96:1654, 2011

7 Once obesity occurs, body fat is defended!

8 Why is the Defense of Body Fat So Important? Body weight (fat mass) is a predictor of survival in Animals Mammals Birds Insects Drosophila larvae Unfortunate circumstances in humans WWII Dutch famine, Leningrad IRA starvation Eckel RH. In: Obesity Mechanisms and Clinical Management. pp. 3-30, 2003

9 Long-Term Follow-Up of Behavioral Treatment for Obesity Kramer, F.M. et al, Int J Obes 13:131, 1989

10 Prevalence of Weight Loss Maintenance in a Biracial Cohort: CARDIA n = 1869 overweight/obese subjects n = 536 (29%) lost 5% between n = 180 (34%) maintained at least 75% between n = 356 (66%) regained Predictors of success African-American race, T2DM, moderate physical activity, emotional support, reduced sugar-containing soft drinks Overall, 34% x 29% = 9% success in those that may have needed weight reduction Phelan S et al, Am Jour Prev Med 39:546, 2010

11 Preservation of Weight Loss by Different Interventions Svetkey LP t al, JAMA 299:1139, 2008

12 The Biology of Reduced Obesity leptin, ghrelin, GLP-1 appetite preference for energy dense foods insulin sensitivity adipose tissue TG lipolysis pro-inflammatory cytokines adipose tissue lipoprotein lipase skeletal muscle lipoprotein lipase CHO oxidation & fat storage physical activity Eckel RH, NEJM, 358:18, 2008

13 ATLPL (nmol FFA/min/10 Change in Adipose Tissue LPL in Response to Insulin and/or Corn Oil 6 cells) 10 8 Insulin Insulin + Corn Oil Normal Wt Obese Reduced Obese Eckel RH and Yost TJ, JCI 80:892, 1987

14 SMLPL (nmol FFA/min/g) Fasting SMLPL Activity in Normal Weight and Obese Women p = Normal Weight before after Obese Eckel RH et al, Eur JCI, 25:396, 1995

15 ATLPL and SMLPL Responses (0-6h) to a High-CHO Diet on Changes in Weight and Fat over 4 Years Outcome Crude model P Effects of 0-6 h changes in ATLPL activity/cell change Adjusted for sex and baseline BMI Weight change Fat mass % Fat change Effects of 0-6 h changes in SMLPL activity/g change Weight change Fat mass % Fat change P

16 fmri, Reduced-Obese > Thin Overfeedng: Hedonic Foods > Basic Objects Cornier M-Aet al, PLoS ONE, 2009

17 How much change in AT mass is needed to be defended? Let s ask this question in walkingwell normal weight women.

18 Subject Characteristics Group Control (n=18) Lipectomy (n=14) P-value Race 15C, 2AA, 1H 12C, 1H, 1Asian NA Weight (kg) <0.005 BMI (kg/m 2 )

19 Patient Amount Suctioned (ml) Suctioning Totals: Surgery Group 11 women had suctioning in hips, thighs, and lower abdomen below the umbilicus 3 women had suctioning in hips and thighs only MEAN 2936 ± 272 ml

20 Weight, kg No Difference in Weight between Baseline and 1-Year Baseline 6 wk 6 mo 1 yr Time Control (n=18) Liposuction (n=14) Question 1: Does fat come back?

21 Change from Baseline (%) Total Body % Fat Changes: DXA Lipectomy Control wk 12 mo Question 2: Where does the fat go?

22 Changes from Baseline (mm) Changes from Baseline (%) Changes from Baseline (cm) Changes from Baseline (cm) Hip Circumference Thigh Circumference Changes Control Lipectomy Control Lipectomy 6 wk 12 mo 6 wk 12 mo Mid Thigh Skin Fold Changes Leg % Fat Changes Control Lipectomy Control Lipectomy wk 12 mo -4 6 wk 12 mo

23 Changes from Baseline (mm) Changes from Baseline (mm) Subscapular Skin Fold Changes (mm) Triceps Skin Fold Changes Control Lipectomy 6 wk 12 mo wk 12 mo Control Lipectomy

24 Changes from Baseline (%) Changes from Baseline (%) Changes in Fat by MRI MRI - Pelvis Relative Fat Area Changes MRI - Thigh Relative Fat Area Changes wk 6 mo 12 mo wk 6 mo 12 mo Control Lipectomy Control Lipectomy

25 Changes from Baseline (%) Changes from Baseline (%) Changes in Abdominal Fat by MRI MRI - Abdominal Subcutaneous Relative Fat Area Changes MRI - Abdomen Visceral Relative Fat Area Changes wk 6 mo Control 12 mo Lipectomy wk 6 mo Control 12 mo Lipectomy

26 So even in walking-well normal weight women, total body fat is defended one year after suction lipectomy - and perhaps in less favorable locations! Hernandez TL et al, Obesity 19: , 2011

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28 Maintenance of Reduced Obesity Energy Intake = Energy Expenditure

29 Klem ML et al, AJCN 66:239, 1997 Weight Loss Maintenance in the National Weight Control Registry Self-reported group of 629 women and 155 men lost an average of 30 kg maintained a required minimum weight loss of 13.6 kg for 5 yr Weight loss achieved by 50% a formal program 50% on their own Both groups reported having used both diet and exercise 77% reported a triggering event 42% of the sample reported that maintaining their weight loss was less difficult than losing weight.

30 Predictors of Weight Loss Maintenance: NWCR Energy Intake avoid frying substitute low-fat for high-fat Leisure Time Exercise # of strenuous activities/wk # of sweat episodes/wk Restraint Scale Concern about dieting Weight fluctuation McGuire, M.T. et al, Obesity Res 7:334, 1999

31 Where s the physician in this whole world of prevention of weight regain after successful treatment of obesity?

32 Why Nutrition and Physical Activity Are Not Addressed by Physicians 1. Drugs and devices are available 2. Don t think lifestyle changes work 3. Not enough knowledge about counseling 4. Insufficient time 5. Not reimbursed 6. Lack of staff (dietitians, exercise therapists) Eckel RH, Circulation 2006, 13:2657

33 The Physician s Ability to Influence Weight Loss Depends on: 1. Being better informed about why patients are unsuccessful in losing weight 2. Understanding why they regain it 3. Learning about individual patients to help them modify their lifestyles Eckel RH, Circulation 2006, 13:2657

34 The 3-Minute Physician Interview Nutrition Daily servings of fruits and vegetables Daily servings of whole grains Weekly servings of fish Saturated and trans fat intake Snack foods, desserts Maximum weight? Food intake pattern Weight loss experience Weight loss desired?

35 The 3-Minute Physician Interview Physical Activity Activity in the job place elevator, escalator, steps Planned activity type and frequency Parking habits close or far Limitations on physical activity Would you like to increase your physical activity?

36 Summary and Conclusions Once obesity occurs, weight loss is difficult to achieve and more difficult to maintain. There is a strong metabolic basis for this. However, success can be achieved. The physician in addition to other members of the health care team must be involved.