1. Primary Care Counseling for Obesity, Nutrition, and Physical Activity 2013 Eileen L. Seeholzer, M.D., MS Associate Prof. - Case Western University School of Medicine Dir. Weight Management and MetroHealthy Wellness Programs Dept. of Medicine and Center for Healthcare Research and Policy MetroHealth Medical Center

2. Objectives To describe the evidence for and tools to provide effective office counseling for:  Obesity  Nutrition  Physical Activity

3. Scope of the problem in the U.S. 1999-2010 data  Prevalence of adult obesity is 36%  Overweight and obesity prevalence is 69%  Overweight + obesity prevalence is 77-80% for non- Hispanic blacks, Hispanics, and Mexican-Americans  Obesity rates highest in lowest socioeconomic levels and in women who self-identify a part of an ethnic minority -rates of obesity 50% in some groups  Obesity prevalence in children and adolescents is 16.9% 1. Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012;307(5):491-497. 2. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA 2012;307(5):483-490.

4. Obesity Risk Higher if:  Female, black (women), Hispanic or and native American  Maternal smoking or diabetes  Lower socioeconomic status  Sedentary lifestyle  Higher fast-food intake  Increased time-spent watching TV  Pregnancy (2-3kg if age 18-30) – ? more in black women  Sleep deprivation (<7 hours nightly, shift work, untreated sleep apnea)  Smoking cessation – average 4-5kg  Medications  Injury/condition impairing ambulation/use of lower extremities

5. Obesity is a chronic disease  There are many definitions of "chronic condition", some more expansive than others. We characterize it as any condition that requires ongoing adjustments by the affected person and interactions with the health care system. © 2006-2011 Improving Chronic Illness Care

6. Obesity is often not reversible: Adipose tissue hyperplasia  At normal BMI ranges usually very little visceral fat is present– largely subcutaneous  With weight gain the adipocytes increase in size and then in number – both hypertrophy and hyperplasia. Hyperplasia may not be reversible  Fat cell hyperplasia can be different depending on individual characteristics and the degree of weight gain. With more weight gain at least some hyperplasia occurs

7. Bray, George. Medications for Obesity: Mechanisms and Applications. Clin Chest Med 30 (2009) 525–538

9. Obesity Treatment Pyramid Diet Physical Activity Lifestyle Modification Pharmacotherapy Surgery NAASO Slide Library

10. Impact of Weight Loss on Risk Factors ~5% Weight Loss 5%-10% Weight Loss HbA1c Blood Pressure Total Cholesterol HDL Cholesterol Triglycerides 1. Wing RR et al. Arch Intern Med. 1987;147:1749-1753; 2. Mertens IL, Van Gaal LF. Obes Res. 2000;8:270- 278; 3. Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S; 4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:264-270. NAASO Slide Library 1 2 3 3 1 2 3 3 4

11. Defining Lifestyle Treatment  Non-drug treatment in which an individual opts to engage and persist in regular activities to prevent, improve, or control a medical condition.  For obesity treatments may include activities affecting: Dietary patterns and content Activity level Sleep quantity and quality Other behavioral habits

12. Eating and Activity Assessment and counseling are necessary medical care  Physicians are required to let a patient know the most effective preventive and treatment tools for chronic disease  A person’s activity and diet are two of their most important medications  Patients want our help to discern where their efforts are best spent

13. Obesity prevention/treatment, healthy diet and physical activity reduce the risk of or prevent many conditions:  Hypertension  Diabetes mellitus type 2  Dyslipidemia  Obstructive sleep apnea  GERD  Asthma  Degenerative disease of weight-bearing joints  Cardiovascular, cerebral, and peripheral vascular disease  Breast, colorectal, and endometrial cancer  Depression and anxiety  Infertility and sexual dysfunction  and several cancers

14. Increased Risks in Pregnancy associated with Obesity  Gestational Diabetes  Hypertension  Disordered breathing/Obstructive Sleep Apnea  Cesarean section rate (RR1.5-1.8)  Congenital heart defects (OR 1.4-2.0)  Spina Bifida (OR 3.5)  Omphalocele (OR 3.3)  Increased levels of leptin, crp and tnf-alpha

15. Obesitytreatment: Healthier eating and active living for life  The goal is to reduce fat mass and preserve or increase lean mass and fitness Diet changes drive weight loss Exercise preserves weight loss and lean mass Pregnancy, menopause, injury, aging, and sedentary life are particular times adipose tissue increase is likely

16. Rationale for Providers to Guide Lifestyle Treatment for Obesity  Patients who improve dietary, activity, and other behavioral recommendations have: better health outcomes, better social outcomes, and reduced mortality

17. Non-Pharmacologic Treatments Weight loss goals of 5-15% considered achievable and sustainable, and improve health Components of Basic Program  Diet Recommendations  Exercise Recommendations  Behavior Therapy  Monitoring and/or follow-up life-long All 4 components needed!

18. Results from Non-pharmacologic Programs  Patients overwhelmingly regain the weight if there is no long-term plan  Behavior therapy and exercise key to weight loss maintenance  High intensity interventions most effective

19. Long-term Weight Loss is Improved with Long-term Maintenance Therapy Weight Loss (%) Perri et al. J Consult Clin Psychol 1988;56:529.NAASO Slide Library 0123456789101112 Time (mo) 1314151617 P <0.05 No maintenance tx Maintenance tx Diet and behavior modification therapy

20. Look AHEAD Unick JL, Beavers D, Bond DS et al. The Long-term Effectiveness of a Lifestyle Intervention in Severely Obese Individuals. Am J Med 2013;126(3):236-242.

21. Commercial Programs Limited studies show:  They can work, are often expensive, none proven superior.  More improvements in lipid profile and fasting sugar results known in low carbohydrate diets, the new Weight Watchers, and Mediterranean diets 1.Rock CL, Flatt SW, Sherwood NE, Karanja N, Pakiz B, Thomson CA. Effect of a free prepared meal and incentivized weight loss program on weight loss and weight loss maintenance in obese and overweight women: a randomized controlled trial. JAMA 2010;304(16):1803-1810 2.Jolly K, Daley A, Adab P et al. A randomised controlled trial to compare a range of commercial or primary care led weight reduction programmes with a minimal intervention control for weight loss in obesity: the Lighten Up trial. BMC Public Health 2010;10:439. 3.Cobiac L, Vos T, Veerman L. Cost-effectiveness of Weight Watchers and the Lighten Up to a Healthy Lifestyle program. Aust N Z J Public Health 2010;34(3):240-247. 4.Brown T, Avenell A, Edmunds LD et al. Systematic review of long-term lifestyle interventions to prevent weight gain and morbidity in adults. Obes Rev 2009;10(6):627-638. 5.Morgan LM, Griffin BA, Millward DJ et al. Comparison of the effects of four commercially available weight-loss programmes on lipid-based cardiovascular risk factors. Public Health Nutr 2009;12(6):799-807.

22. Panel B shows the change in weight for each of the dietary Groups during the weight- maintenance intervention, adjusted for body-mass index at randomization, Weight loss during the low- calorie-diet phase, sex, family Type (single-parent family, two- parent family with one parent as participant, or two-parent family with both parents as participants), center, and age at screening, on the basis of an intention-to-treat mixed- model analysis. The changes in body weight from randomization to week 26 among participants who completed the intervention are also shown (boxes). HGI denotes high glycemic index, HP high protein, LGI low glycemic index, and LP low protein. Larsen TM, Dalskov SM, van BM, et al. Diets with high or low protein content and glycemic index for weight-loss maintenance. N.Engl.J.Med. 2010 Nov 25;363(22):2102-13

23. Eat a lower-calorie diet WomenCalorie guide (Kcal) Shorter, post-menopausal, less active1000-1200 Average height, moderately active1200-1400 Younger, taller, moderately to very active women1400-1800 Men Shorter, less active1400-1600 Average height, moderately active1800-2000 Younger, taller, moderately to very active2000-2200

24. Healthy plate

25. Prudent Dietary Recommendations for addressing obesity and cardiovascular risk factors Low SFA (<7%), TFA (<1%), dietary cholesterol (<200mg) Rich in PUFA ample fiber 30g/day – soluble fiber emphasis nuts as able 1 oz a day and other soy and legumes lean dairy 5-7 servings of fruits and vegetables daily limit sugary beverages limit refined foods rich in whole grains Energy balanced to prevent weight gain Avoid high salt food – over 450mg/serving and <2000mg/day For many, a low calorie diet that is low in fat and refined carbohydrates is best for long-term adherence Van HL, McCoin M, Kris-Etherton PM et al. The evidence for dietary prevention and treatment of cardiovascular disease. J Am Diet Assoc 2008;108(2):287-33

26. Dietary Recommendations  Low-calorie diet better than very-low calorie diet for maintaining weight loss  Meal replacements (e.g. South Beach, Atkins, Slimfast or Glucerna) often helpful in improving success with dietary caloric adherence – best if >12g-14g protein, >5gm fiber, <7grams sugar  Portion-controlled servings also useful for weight loss adherence

27. Diet Recommendations  Can be achieved with plans – do not need to count- few people can count accurately  Planning, routinizing, and tracking support success  Encourage use of low or no-cost supports for both ideas and tracking like: myfitnesspal.com and sparkpeople.com

28. Bray, George. Medications for Obesity: Mechanisms and Applications. Clin Chest Med 30 (2009) 525–538

29. What modifies the REE over time?  Aerobic exercise from 40-60 minutes can raise REE the following day for 19- 24 hours  Caffeine mildly raises REE  Resistance work over time will increase lean mass and raise REE for that weight  Calorie restriction lowers REE  Weight loss of 10-20% reduces REE – (lasts at least 3-5 years)

30. Effect of exercise on body composition and energy expenditure Moderate to vigorous aerobic activity of 35 minutes or more increases RMR the following day Regular resistance exercise slows or prevents the loss of lean mass, preserving a higher RMR and insulin sensitivity All activity has calorie output

32. Activity as a single intervention Buchner DM. Physical activity and prevention of cardiovascular disease in older adults. Clin Geriatr Med 2009;25(4):661-75, viii.

34. What exercise is Recommended?  CDC/ACSM -1993: 30 min. of moderate activity most/all days of the week (also endorsed by ACOG 2012 for pregnant women with no contraindications)  AHA – 2003: 30-60 min. of activity 4-6x weekly and resistance training 2-3 x weekly  IOM - 2003: 60 minutes of physical activity daily  USPSTF – 2012: avoid inactivity; be physically active > 150 minutes/week; include muscle- strengthening activities twice weekly or more (endorsed by AAFP)

35. General Exercise Goal Recommendations  Aerobic Activity: 30-60 minutes of moderate to vigorous activity most days of the week (e.g. brisk walking, stationary bike, swimming)  Strengthening/Resistance 3 days a week

36. When do I prescribe Exercise?  Research shows effective counseling can be done in about 5 minutes  Research shows patients who are counseled to exercise by physicians have higher activity levels in the year following the counseling Calfas, K. J.; Long, B. J.et.al. A controlled trial of physician counseling to promote the adoption of physical activity. Prev Med. 1996 May-1996 Jun 30; 25(3):225-33. Long, B. J.; Calfas, K. J, et.al. A multisite field test of the acceptability of physical activity counseling in primary care: project PACE. Am J Prev Med. 1996 Mar-1996 Apr 30; 12(2):73-81. Lewis, B. S. and Lynch, W. D. The effect of physician advice on exercise behavior. Prev Med. 1993 Jan; 22(1):110- 21.

37. Where does a patient begin  Reducing TV time is a free way for a patient to reduce sedentary activity and possibly reduce calories  Activities should include safe, weather independent, and cost neutral options  Activities should be chosen in part on patients personal preference  Scheduling time or making daily weekly goals help patients maintain routines (step/day or minute/week goals)  Small bouts at work / home

38. Assessing Weight Loss Readiness  Motivation: Patient is ready to make long-term changes in activity AND diet to lead to a lower weight  Stress level: Patient is free of major life crises  Psychiatric issues: Patient does not have untreated or under treated depression, substance abuse, bulimia nervosa  Medical issues: Patient medical problems are stable  Time availability: Patient can devote 15-30 min/d to weight control for next 26 weeks Patient Ready? Prevent weight gain and explore barriers to weight reduction Initiate weight loss therapy YESNO Clinical Guidelines on the Identification, Evaluation and Treatment of overweight and Obesity in Adults, NIH – NHLBI 1998

39. Assess values and motivators  The effort of lifestyle change is great  Motivations vary  Persistence is linked to how connected a person is to his or her motivator  Values like responsibility, self-concern, and honesty may be key to making and adapting plans

40. Four Components of Successful Weight Loss Weight loss goal Monitoring weight loss Regular physical activity Low calorie diet

41. Build in Monitoring - Success and persistence linked to keeping records or high structure  Journal  Reflect on data  Daily to weekly weights  Goal setting

42. Lifestyle management: Processes to be tended and amended Sustainable Choices fit  Values  Plans to reduce barriers  Preferences – convenience, type  Resources – time, money, place  Finances  Ability

43. Lifestyle management: Connect patients to local resources  Refer to programs – nutritionists, Weight management clinic, behaviorists, appropriate commercial diets, self-help groups, local recreation centers, local produce programs  Encourage investigation and experimentation  Encourage persistence, flexibility, and hope

44. Document the plan  Type of goal: dietary, activity, other  Tools to achieve: stuff, time, people, places, skills, knowledge  Date for start  Resources needed: people, places things  Anticipated barriers  Strategies  Assess and redesign

45. How do I follow-up with clients/patients?  Research shows that appointments 1-2 times a month for at least 16 weeks are most effective in establishing behavior changes. Long-term frequent follow-up needed for maintenance.  Follow-up can be in person, group visit, on-line or by phone

46. Pick your counseling tool  Solution-focused brief therapy  5 As  Motivational interviewing  Personal improvement (systems approach)  Diet and activity prescriptions Make your approach:  Non-judgmental  Patient-centered  Focused  Documentation friendly

48. Regulation of Food Intake Brain NPY AGRP galanin Orexin-A dynorphin Stimulate α-MSH CRH/UCN GLP-I CART NE 5-HT Inhibit Central Signals Glucose CCK, GLP-1, Apo-A-IV Vagal afferents Insulin Ghrelin Leptin Cortisol Peripheral signals Peripheral organs +   + Gastrointestinal tract Adipose tissue Food Intake Adrenal glands External factors Emotions Food characteristics Lifestyle behaviors Environmental cues NAASO Slide Library

49. Drugs Approved by FDA for Treating Obesity Orlistat (Xenical) Lorcaserin (Belviq) Phentermine-topiramate (Qsymia) Phentermine (Adipex-P, Suprenza). (short-term only)

50.  Obesity is not fair  Other diseases promote obesity and impede its treatment  How much and how well we sleep matters  It really is unfair for women – pregnancy, motherhood, and menopause provide additional challenges and opportunities  Obesity is not always reversible, and its control with treatment is variable  Average activity levels currently lead to decreased lean mass quantity and quality. This decrease has profound implications for obesity and chronic disease prevention and treatment  Exercise cannot over-come high calorie-dense foods for many people Key Knowledge about obesity that change treatment approach

51.  It is not just calories – protein, fiber, fat composition, sugar, and other factors affect: satiety and satiation, blood pressure, lipids, insulin sensitivity  Some foods make you hungry  When we eat matters  The goal is to teach people basic concepts to assess, adjust and adapt as change is relentless  Healthcare providers have more impact when they are engaged, not perfect, in making healthy lifestyle choices  The environment matters-  While everyone does not get “sick” in high risk environments, fewer can stay well, get better, improve optimally  We all work harder to make good choices in less healthy environments – do we really want to work that hard? Key Knowledge about obesity that changes treatment approach

52. Conclusion  Obesity is a chronic disease influenced by multiple endocrine pathways that influence eating behaviors and activity levels  Neuroendocrine substances that are made in the brain, the gastrointestinal system, and the adipose tissue are just being elucidated.  Obesity treatment requires behavioral treatment and may require pharmacologic and sometimes invasive treatment to produce optimal disease control

53. Obesity Treatment Guidelines The Practical Guide can be found at: NHLBI web site: www.nhlbi.nih.gov The Obesity Society web site: www.obesity.org

54. Obesity-Related Resources Professional Associations The Obesity Society American Academy of Family Physicians (AAFP) American College of Sports Medicine (ACSM) American Diabetes Association (ADA) American Dietetic Association (ADA) American Gastroenterological Association (AGA) American Heart Association (AOA) American Obesity Association (AOA) American Society for Bariatric Surgery (ASBS) www.obesity.org www.aafp.org www.acsm.org www.diabetes.org www.eatright.org www.gastro.org www.americanheart.org www.obesity.org www.asbs.org

55. Centers for Disease Control (CDC): Obesity and Overweight Centers for Disease Control (CDC): Prevalence data and growth charts National Institutes of Health (NIH) National Institutes of Diabetes & Digestive & Kidney Diseases (NIDDK) Weight-Control Information Network (WIN) National Institutes of Diabetes & Digestive & Kidney Diseases (NIDDK) Weight Loss and Control National Library of Medicine, MEDLINE Plus Obesity-Related Resources Government Organizations www.cdc.gov/nccdphp/dnpa/obesity/ index.htm www.cdc.gov/nchs/nhanes.htm www.nih.gov www.niddk.nih.gov/health/nutrit/win.htm www.niddk.nih.gov/health/nutrit/nutrit. htm www.nlm.nih.gov/medlineplus/obesity. html

57. Weight friendly medications NOT approved for Obesity treatment  Anti-epileptics Topiramate Zonisamide  Incretins Exenatide Liraglutide Pramlintide and other amylin analogues

58. Effect of Continuous and Intermittent Phentermine Therapy on Body Weight (Short-term only approved) 0 Time (weeks) 82428 Munro JF et al. Brit Med J 1:352, 1968NAASO Slide Library Weight Loss (lbs) 36412162032 Alternate Phentermine and Dummy Continuous Phentermine Continuous Dummy

59. Allison DB, Gadde KM, Garvey WT et al. Controlled-Release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial (EQUIP). Obesity (Silver Spring) 2012;20(2):330-342.

60. Controlled-Release Phentermine/Topiramate in Severely Obese Adults

61. Allison DB, Gadde KM, Garvey WT et al. Controlled-Release Phentermine/Topiramate in Severely Obese Adults: A Randomized Controlled Trial (EQUIP). Obesity (Silver Spring) 2012;20(2):330-342. Controlled-Release Phentermine/Topiramate in Severely Obese Adults

62. Orlistat Prevents Fat Digestion and Absorption by Binding to Gastrointestinal Lipases TG=triglyceride; MG=monoglyceride; FA=fatty acid. NAASO Slide Libary Mucosal Cell Intestinal Lumen Orlistat TG LIPASE LIPASE LIPASE Bile Acids Micelle MG FA

63. Effect of Long-term Orlistat Therapy on Body Weight 0 Weeks 52 Torgenson et al. Diabetes Care 2004;27:155NAASO Slide Library Change in Weight (kg) 104156208 P<0.001 vs placebo -4.1 kg -6.9 kg Placebo Orlistat

64. Meta-analysis of RCTs Evaluating Effect of Orlistat Therapy on Weight Loss at 1-Year Study or Sub-category WMD (random) 95% CI Hollander 1998* Sjostrom 1998 Davidson 1999 Finer 2000 Heuptman 2000 Lindgarde 2000 Rossner 2000 Bakris 2002 Broom 2002 Kelley 2002* Miles 2002* Total (95% CI) Padwal et al. Int J Obes 2003;27:1437 *All subjects had type 2 diabetes WMD=weighted mean difference Favours Treatment Favours Control -10-50105

65. Food and the Incretins: Glucagon-like-peptide (GLP-1)  Site of Synthesis: secreted of the L- cells distal small intestine, Also made in the NTS, hypothalamus and amygdala  Site(s) of action: Inhibits NPY neurons and stimulates the POMC system, PYY decreases ghrelin levels, activates neurons in the area postrema of the PVN  Factors affecting production: secreted in response to rapid passage of food to hindgut with contact with chyme  Major known effects: increases insulin secretion and increases insulin sensitivity. It leads to decreased food ingestion and weight.

66. GLP-1 receptor agonists (i.e. exenatide, liraglutide)  Mechanism: long-acting synthetic peptide that is a GLP-1 receptor agonist Currently twice daily or daily subcutaneous dosing Weekly dosing in release  Side effects: Most common is nausea Hypoglycemia as discussed prior Weight loss ?increase in INR in patients on coumadin Local reaction/allergy ?rare pancreatitis

69. TABLE 1 -- Potential targets for new obesity treatments Agonists/stimulators  Adiponectin  2αMSH/MC4R  Apolipoprotein A-IV  Brain-derived neurotrophic factor/TrkB receptor  CCK/CCK-A receptor CNTF/axokine  Cocaine- and amphetaimine-regulated transcript  GLP-1/exendin-4 Human GH fragment (AOD9604)  Insulin mimetics  Leptin; leptin receptor Oxyntomodulin  PYY  Phosphatidylinositol 3-kinase  Somatostatin  β3, serotonin, norepinephrine, dopamine receptors Antagonists/inhibitors  Acetyl CoA carboxylase Agouti-related protein 11βHSD1  Central CPT1  CRH receptor  DP-IV  Endocannabinoid receptor (rimonabant/SR141716A)  Fatty acid synthase (cerulenin; C75)  Galanin  GIP  Ghrelin  Histamine receptor  MCH  NPY  Orexin A and B  Suppressor of cytokine signaling-3  Tyrosine phosphatase IB Korner J - J Clin Endocrinol Metab - 01-JUN-2004; 89(6): 2616-21

71. Brethauer, Stacy A. Sleeve Gastrectomy. Surgical Clinics of North America; Volume 91, Issue 6 (December 2011).

72. Heneghan HM, Meron-Eldar S, Brethauer SA, Schauer PR, Young JB. Effect of bariatric surgery on cardiovascular risk profile. Am J Cardiol 2011;108(10):1499-1507.

73. Mackey RH, Belle SH, Courcoulas AP et al. Distribution of 10-year and lifetime predicted risk for cardiovascular disease prior to surgery in the longitudinal assessment of bariatric surgery-2 study. Am J Cardiol 2012;110(8):1130-1137.

75. Bariatric Outcomes from SOS  The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls between Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls  MAIN OUTCOME : The primary end point of the SOS study (total mortality) There were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio was 0.76 in the surgery group (P=0.04), as compared with the control group, and the hazard ratio adjusted for sex, age, and risk factors was 0.71 (P=0.01). The most common causes of death were myocardial infarction (control group, 25 subjects; surgery group, 13 subjects) and cancer (control group, 47; surgery group, 29).  Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P =.002). The number of total first time (fatal or nonfatal) cardiovascular events was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P <.001). average of 10.9 years of follow-up. 1.Sjostrom L, Peltonen M, Jacobson P et al. Bariatric surgery and long-term cardiovascular events. JAMA 2012;307(1):56-65. 2.Sjostrom L, Narbro K, Sjostrom CD et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357(8):741-752

76. Heneghan HM, Meron-Eldar S, Brethauer SA, Schauer PR, Young JB. Effect of bariatric surgery on cardiovascular risk profile. Am J Cardiol 2011;108(10):1499-1507.

81. Brethauer, Stacy A. Sleeve Gastrectomy. Surgical Clinics of North America; Volume 91, Issue 6 (December 2011).

82. Comparison of surgical and lifestyle intervention for obesity on DM and cardiovascular risk factors Hofso D, Nordstrand N, Johnson LK et al. Obesity-related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention. Eur J Endocrinol 2010;163(5):735-745. DESIGN: One-year controlled clinical trial METHODS: Morbidly obese subjects (19-66 years, mean (s.d.) body mass index 45.1 kg/m(2) (5.6), 103 women) were treated with either Roux-en-Y gastric bypass surgery (n=80) or intensive lifestyle intervention at a rehabilitation centre (n=66). The dropout rate within both groups was 5%. RESULTS: Among the 76 completers in the surgery group and the 63 completers in the lifestyle group, mean (s.d.) 1-year weight loss was 30% (8) and 8% (9) respectively. Beneficial effects on glucose metabolism, blood pressure, lipids and low-grade inflammation were observed in both groups. Remission rates of type 2 diabetes and hypertension were significantly higher in the surgery group than the lifestyle intervention group; 70 vs 33%, P=0.027, and 49 vs 23%, P=0.016. The improvements in glycaemic control and blood pressure were mediated by weight reduction. The surgery group experienced a significantly greater reduction in the prevalence of metabolic syndrome, albuminuria and electrocardiographic left ventricular hypertrophy than the lifestyle group. Gastrointestinal symptoms and symptomatic postprandial hypoglycaemia developed more frequently after gastric bypass surgery than after lifestyle intervention. There were no deaths. CONCLUSIONS: Type 2 diabetes and obesity-related cardiovascular risk factors were improved after both treatment strategies. However, the improvements were greatest in those patients treated with gastric bypass surgery. Citation: