Physiology of weight regain Current dietary interventions for weight regain SUE CUMMINGS, MS, RD

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1 Physiology of weight regain Current dietary interventions for weight regain SUE CUMMINGS, MS, RD

2 Starting Principles: Causes of Obesity Obesity is a chronic disease that is: both biopsychosocially complex in its origins and clinically diverse in its presentation Susceptibility to obesity and its associated risks vary greatly from one person to the next within obesogenic environments BMC Med. 2010; 8: 88.

3 Starting Principles Body energy storage is maintained at a set level through a complex weight regulatory system. Deviations from the preferred set level are resisted and minimized by a complex feedback control system Clinical Science (2013) 124, Priya Sumithran and Joseph Proietto

4 Defense against Starvation Our bodies seek a Stable Adipose Tissue Mass not unlike body temperature, blood volume Diet-induced weight loss is accompanied by physiological adaptations which encourage weight regain

5 Gut messengers involved in Weight Regulation Clinical Science (2013) 124, Priya Sumithran and Joseph Proietto

6 Key Hormone Changes Associated with Weight Loss and Regain Hormone Source Normal function Cholecystokinin (CCK) Duodenum Suppress appetite Ghrelin Gastric fundus Stimulate appetite, particularly for highfat, high-sugar foods Glucagon-like peptide 1 (GLP-1) Ileum Suppress appetite and increase satiety Peptide YY (PYY) Distal small intestine Suppress appetite Amylin Pancreas slowing gastric emptying and promoting satiety Leptin Adipocytes Regulate energy balance Suppress appetite Sumithran P, Proietto J. Clin Sci (Lond). 2013;124:

7 Amylin Ghrelin CCK PYY Gut Hormone Changes Persistently Oppose Dietinduced Weight Loss Sumithran et al. NEJM 2011; 365:

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9 Bariatric procedures, by restructuring the gut: Influence the body weight regulatory system gut hormones, neural messaging and gut microbiota new defended body weight (new set point) all mechanisms not known: decreased hunger, increased satiety, defense of lbm, energy expenditure (Hao X, et al. Obesity, Feb. 2016)

10 GI Endocrine Responses to RYGB Active GLP-1 (pg/ml) GLP-1 * 5 min mixed meal * * Time after start of meal (min) Ghrelin # RYGB Sham Lean * PYY (pg/ml) * PYY 5 min mixed meal * * * * * RYGB Sham Lean * Time after start of meal (min) Active Amylin (pg/ml) Amylin 5 min mixed meal * * Time after start of meal (min) Acylated Ghrelin (pg/ml) 5 min mixed meal 300 RYGB Sham 250 Lean Shin et al., 2010 * * Time after start of meal (min)

11 Effective treatment: changes set point BMI Unhealthy lifestyle Dieting

12 Effective treatment changes set point BMI Unhealthy lifestyle Dieting Rebound higher weight

13 Effective treatment changes set point BMI Unhealthy lifestyle Dieting rebound Healthy lifestyle

14 Effective treatment changes set point BMI Unhealthy lifestyle Healthy lifestyle Medication + Healthy lifestyle

15 Effective treatment changes set point BMI Unhealthy lifestyle Healthy lifestyle Medication + Healthy lifestyle Surgery + Healthy lifestyle

16 Obesity is a Heterogenetic Disease Despite the profound effects of bariatric surgery on energy balance and glucose homeostasis, outcomes in individual patients vary widely. Most patients will not lose 100% of excess weight Therefore, it is important to manage expectations both in terms of amount of weight loss and weight regain

17 Weight Loss Variability Every bariatric procedure studied demonstrates similar wide variations in outcome among patients. RYGB SG

18 Managing Weight Loss Expectations

19 Weight Loss Response to surgery is broadly distributed Inadequate Weight Loss: Failure to achieve and maintain expected weight loss after a bariatric procedure (<20%) Gastric Bypass Sleeve Gastrectomy GS: Definition for inadequate weight loss was EWL< 42%.

20 Implications: Inadequate Weight Loss Inadequate Weight Loss: a failure to lose significant weight despite the major anatomic and physiological effects of surgery Inadequate weight loss is a biological event Not always predictable Requires careful assessment and varied approaches Aim of treatment is to enhance set point Optimization of life style/environment is essential May require conversion surgery Combination Therapies Addition of pharmacological therapies may be effective

21 Weight Loss and Regain Even in those patients who have significant weight loss; weight regain occurs in variable amounts READY TO GO BACK?

22 15-25% of the lost weight regained over a period of 10 years *Swedish Obesity Subjects: Diabetes Prevention Program

23 Causes of weight regain should be fully evaluated Anatomical Clinical Factors Physiological Nutrition / Behavioral Gastric Bypass G-G fistula Pouch Enlargement G-J Anastomosis Dilation Gastric Banding Band Migration Band Loosening

24 Environmental Modulators of Energy Balance

25 Obesity is a Heterogenetic Disease MACRO- MICRO-ENVIRONMEMT Food Industry Built Environment Socio-political & Cultural Influences Media Work Schedules Depression Eating Disorders Treatable Issues Anxiety Other psychiatric issues Diet Activity Stress Modifiable Factors Sleep Circadian Rhythm Intrauterine Environment Childhood Developmental Effects Puberty Pregnancy Menopause Genes Age Fixed Factors Gender Race Adipose Biology Medication Ahmad N et al. Obstet Gynecol Clin North Am

26 Life Style Influences: Amenable to Change Inadequate physical activity Processed diets Irregular eating pattern Inadequate sleep Stress Weight increasing medications Life changes (aging, pregnancy, menopause)

27 Post-Operative Eating behaviors Increased stress and pace of life Chaotic eating patterns Skipped meals Unhealthier food choices

28 Disrupted eating patterns Proceedings of the Nutrition Society, Page 1 of 1 doi: /s

29 Meal Timing When combatting the effects of chronic disease, food timing has emerged as a new approach to the treatment of obesity and the metabolic syndrome. Regular eating habits might facilitate weight balance Proceedings of the Nutrition Society, Page 1 of 1 doi: /s Curr Obes Rep Mar;4(1):11-8. doi: /s y.

30 Probe for life style factors that may influence weight: A. Eating the majority of calories in late evening B. Skipping breakfast, grazing throughout the day, eating a high calorie, high fat dinner meal C. Working night or graveyard shift

31 Weight Regain Disruption of circadian clocks by genetic and/or environmental factors precipitate numerous common disorders, including Obesity. Gamble, K. L. et al. (2014) Circadian clock control of endocrine factors Nat. Rev. Endocrinol. doi: /nrendo

32 How does meal timing influence weight Diet-induced thermogenesis (DIT) 50% lower in circadian evening than morning Theoretically can contribute to positive energy balance when eating is late Morris et al, Obesity, 2015

33 Circadian Rhythm Multiple genes and hormones that are involved in energy regulation and nutrient metabolism display rhythmic oscillations Shift workers have higher rates of obesity (police, airline personnel, healthcare providers, etc) Ghrelin Cortisol INCREASED APPETITE Leptin

34 Ghrelin: Suppressed Longest by Protein Foster-Schubert et al. JCEM. 2008; 93(5): Lomenick et al. JCEM. 2009; 94(11):

35 Planning/Preparing OPTIMAL DISTRIBUTION of PROTEIN Enhance Satiety Addition of a protein food at each meal and mid morning, mid-afternoon and evening snacks B L D S S S Millward DJ, Layman DK, Tme D, Schaafsma G. Protein quality assessment: impact of expanding understanding of protein and amino acid needs for optimal health Am J Clin Nutr May 2008 vol. 87 no S-1581S.

36 Stress There is significant evidence suggesting potentially detrimental effects of stress on Increased binge eating Eating patterns (skipping meals) Increased preference and consumption of HIGHLY PALATABLE (high sugar/fat/salt) Stress as a Common Risk Factor for Obesity and Addiction Sinha, Rajita, Biological Psychiatry, Volume 73, Issue 9, Brunner EJ, et al Am J Epidemiol, 2008:165: Adam TC, Epel ES. Physiol Behav. 2008;91(4): Evans GW, et al Pediatrics.2012;129(1):e68-73

37 Stress Increased Cortisol Insulin resistance Hyperinsulinemia Leptin Resistance Decreased Metabolic Rate and Increased Food Intake Increased Hedonic Drive and Consumption of Palatable Foods Sinha R, Jastreboff AM. Biol Psychiatry. 2013; 73(9):

38 Dietitian can address: Eating patterns structure; planning, preparing Protein distribution Healthier Foods 1. Address Barriers to making Life Style changes 2. Provide patient with tools/techniques Teaching how to reduce/manage Stress

39 Reactive hypoglycemia ( late dumping ) Occurs within a few hours after a meal, is caused by an overproduction of insulin Symptoms include sweating, shakiness, loss of concentration, hunger, and fainting or passing out. Reported to occur: 2-9 years after RYGB

40 Ukleja 2006 Triggers to Weight Gain: Reactive Hypoglycemia I I I I I GIP GLP-1 Food moves to jejunum quickly; triggers hormone release (GLP-1 and GIP) which stimulates insulin response

41 Suspected Reactive Hypoglycemia OGTT Signs/Sx Food records/ SBGM 46

42 Post-Operative Hypoglycemia Manage with dietary manipulation Avoid high sugar/refined carbohydrate foods. 6 small meal; protein source at each

43 Suspected Reactive Hypoglycemia OGTT Signs/Sx Food records/ SBGM

44 Patients who present with severe post-prandial symptoms of hypoglycemia unresponsive to diet manipulation or medication, need further endocrine evaluation Tack J, et al Nature Reviews Gastroenterology & Hepatology (6) (2009) Consider the possibility of insulinoma or nesidioblastosis of the pancreas

45 What about Diet Quality? GUT MICROBIOTA Play an important role in: regulation of energy balance development and progression of obesity and other metabolic disorders, including type 2 diabetes Gut Microbiota differ between individuals who are lean and individuals with obesity

46 Individual with Obesity Increased Firmicutes Increased Bacteroidales

47 Bypass and Sleeve: Alter Microbiota RYGB and SG in a mouse model alters the microbiota independent of weight loss The altered by Microbiota contribute to several metabolic outcomes that influence: body weight adiposity lipids insulin Liou A, Kaplan LM et al., Sci Transl Med 2013

48 Diet accounts for 57% of variation in microbiota

49 Post-Op Regain: Is it More than Just Calories? High consumption of: o red and processed meat o sugary desserts and drinks o high fat foods o refined grains Associated with: o significant increase in Firmicutes (unfavorable); and o significant decrease in Bacteroidetes (favorable)

50 Food Additives and Gut Microbiota Dietary emulsifiers are added to many processed foods to improve texture and extend shelf life contribute to unfavorable microbiome Source: Chassaing B, Gewirtz AT, Koren O, Goodrich JK, Poole AC, Srinivasan S, and Ley RE. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015

51 What we eat Matter? Is It more than Calories? Healthy diet Prebiotics, Probiotics Environmental Factors

52 Maintaining Favorable Microbiota: Potential Therapeutics Probiotics are the naturally occurring, friendly bacteria that help maintain a healthy intestinal tract. Prebiotics are the substances that help fuel probiotics. They are fermentable fibers. Prebiotics stimulate the growth of probiotics, helping them to thrive in your gastrointestinal tract.

53 Post-surgery Regain Therefore, think quality versus quantity.

54 Weight Regain and Inactivity Epidemiologic, cross-sectional, and prospective correlation studies suggest an essential role for physical activity in weight-loss maintenance prospective trials shows a clear dose response relationship between physical activity and weight maintenance. Mozaffarian, NEJM, 2011

55 Medications that Promote Weight Gain CNS drugs Endocrine agents Miscellaneous Atypical Antipsychotics eg. olanzipine Anti-epileptics eg.valproate Lithium Anti-depressants SSRIs eg. paroxetine Tricyclic agents eg. nortriptyline Others eg. venlafaxine,mirtazapine Glucocorticoids eg. prednisone Hormonal contraceptives eg. medroxyprogesterone Diabetes agents Insulin Sulfonylureas eg. glyburide Thiazolidenediones eg. pioglitazone, Beta blockers eg. metoprolol Antihistamines eg. diphenhydramine Sleep aids eg. zolpidem Leslie, et al. QJM. 2007;100:

56 SUMMARY Address environmental triggers to weight regain chaotic meal / snack patterns stress management sleep hygiene shift workers An individualized diet is the basis of the dietary component of a comprehensive weight management program.. focus on real food vs high consumption of food like intake Protein intake distributed throughout day at meals/snacks (~30 g/meal) Encourage exercise prescription Assess for weight promoting medications

57 THANK YOU QUESTIONS?