Improvements in Long-Term Appetite-Regulating Hormones in Response to a Combined Lifestyle Intervention for Obesity

Abstract Altered levels of hormonal appetite regulators have been observed in obesity (BMI ≥ 30.0 kg/m2), most prominently increases of insulin and leptin (indicating resistance) as well as decreases of adiponectin - all of which are long-term energy regulators and adiposity signals. Disrupted signaling of these hormones may have detrimental effects on metabolism, but may also promote weight gain. Weight loss is often accompanied by normalizations of long-term adiposity signals, but findings concerning short-term appetite regulators after weight loss vary across interventions (e.g. very low calorie diets vs. exercise). Moreover, it is debated whether such weight-loss-induced hormonal changes may reflect a disposition for weight regain. Here, we investigated changes of long- and short-term appetite signals in response to an intensive 75-week combined lifestyle intervention (CLI) comprising a normocaloric healthy diet, physical activity and psychotherapy to promote improved long-term weight management. For 39 patients, data on fasting serum levels of appetite-regulating hormones (leptin, insulin, adiponectin, GIP, PP, PYY, CCK, FGF21) were available. Hormone levels were correlated to BMI at baseline (T0) and compared across three time points: T0, T1 (after 10 weeks; initial weight loss) and T2 (after 75 weeks; weight loss maintenance). T0-T1 hormone changes were correlated to BMI changes between T1 and T2 to investigate whether hormonal alterations during initial weight loss are associated with weight regain. At T0, hormone levels were not associated with BMI. BMI decreased significantly from T0 (40.13 kg/m2 ± 5.7) to T1 (38.2 ± 5.4, p < .001) which was maintained at T2 (38.2 kg/m2 ± 5.9, p < .001). There were no significant changes in GIP, PP, PYY, CCK and FGF21. Leptin decreased from T0 (44.9 ng/nl ± 15.3) to T1 (33 ng/nl ± 14.8, p < .001) and T2 (38.6 ng/nl ± 16.0, p < .01), just like insulin which was significantly decreased at T1 (123 pmol/l ± 65, p < .05) and T2 (128 pmol/l ± 64, p < .05) compared to T0 (160 pmol/l ± 80). Adiponectin did not change between T0 (3.36 ug/ml ± 2.1) and T1 (3.2 ug/ml ± 2.1), but was increased at T2 (3.7 ug/ml ± 2.9, p < .01) compared to T1. T0-T2 BMI decrease correlated positively with T0-T2 decreases in leptin (r = .667, p < .001), insulin (rho = .535, p < .001) and increases of adiponectin (r = .412, p < .01), but no other hormone. T0-T1 hormone changes did not predict T1-T2 BMI changes. Thus, a 75-week CLI was associated with beneficial changes in the long-term energy regulators adiponectin, leptin and insulin, but no changes in short-term appetite-regulating hormones were observed despite significant weight loss. Initial changes in appetite-regulating hormones were not associated with subsequent weight regain. Overall, our data suggest that a CLI does not lead to adverse changes in appetite regulation, but rather long-term improvements such as e.g. increased leptin and insulin sensitivity.

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MON-LB101 5-Year Data of an Aggressive Pharmacological Approach to Moderate and Morbid Obesity: Is Prevention of Bariatric Surgery Feasible in the Long Run?

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2340 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Flavio Cadegiani

Keyword(s):

Bariatric Surgery ◽

Morbid Obesity ◽

Weight Loss ◽

Body Weight ◽

Weight Regain ◽

Morbidly Obese ◽

Biochemical Profile ◽

Initial Weight ◽

Initial Weight Loss

Abstract Background: Maintenance of weight loss in patients that undergo weight loss interventions is highly challenging, irrespective of the type of approach to obesity (whether surgical, pharmacological, or non-pharmacological). We proposed a protocol of an aggressive clinical treatment for obesity aiming to prevent the need of bariatric surgery, in patients unwilling to undergo this procedure, by proposing a protocol that included the combination of different anti-obesity medications and non-pharmacological modalities, for longer duration, and with an active approach to prevent weight regain. Our initial 2-year data showed that 93% (40 of 43 patients) with moderate and morbid obesity were able to avoid the need of bariatric surgery, with concomitant improvements of the biochemical profile. However, whether these patients would maintain their successful rates after five years was uncertain. Our objective is to describe the efficacy and safety of a long term (5-year data) pharmacological and multi-modal treatment for moderate and severe obesity. Methods: The 40 patients that were successful in the two-year approach in our obesity center (Corpometria Institute, Brasilia, DF, Brazil) were enrolled. A long-term anti-obesity protocol was employed, with continuous or intermittent use of anti-obesity drugs, trimestral body composition analysis, psychotherapy, visit to a nutritionist every four months, and both resistance and endurance exercises at least four times a week. Body weight (BW), total weight excess (TWE), body fat, markers of lipid and glucose metabolism, liver function, and inflammation were analyzed. Subjects that dropped out were considered as weight regain. Therapeutic success for the 5-year follow-up included as the maintenance of >20% loss of the initial BW loss, and no weight regain (or < 20% of the initial weight loss). Results: A total of 27 patients (67.5%) were able to maintain the body weight, seven dropped out, and six regained more than 20% of the initial weight loss. Of these, 21 (77.8%) had significant further increase of muscle mass and decrease of fat loss, while 17 (63.0%) had further weight loss (p < 0.05), compared to the 2-year data. Improvements on the biochemical profile persisted in all 27 patients, and had significant further improvements in 24 (88.9%) of these patients. Conclusion: The risk of weight regain five years after a weight loss treatment for obesity was significantly lower compared to previous literature, and comparable to the long-term outcomes of bariatric procedures. An aggressive, structured, and long-term clinical weight loss approach has been shown to be feasible, even for morbidly obese patients.

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Management of Obesity

Journal of Clinical Oncology ◽

10.1200/jco.2016.66.8806 ◽

2016 ◽

Vol 34 (35) ◽

pp. 4295-4305 ◽

Cited By ~ 22

Author(s):

Naji Alamuddin ◽

Zayna Bakizada ◽

Thomas A. Wadden

Keyword(s):

Physical Activity ◽

Bariatric Surgery ◽

Weight Loss ◽

Lifestyle Intervention ◽

Weight Regain ◽

Initial Weight ◽

The Us ◽

And Behavior

This review examines weight loss and accompanying improvements in obesity-related comorbidities produced by intensive lifestyle intervention, pharmacotherapy, and bariatric surgery. Obese individuals lose approximately 6 to 8 kg (approximately 6% to 8% of initial weight) with 6 months of participation in a high-intensity lifestyle intervention (≥ 14 treatment visits) consisting of diet, physical activity, and behavior therapy. Such losses reduce progression to type 2 diabetes in at-risk people and decrease blood pressure and triglyceride levels. All diets, regardless of macronutrient composition, can produce clinically meaningful weight loss (> 5%) if they induce a deficit ≥ 500 kcal/d. Physical activity of 150 to 180 min/wk yields modest short-term weight loss compared with diet but contributes to improvements in obesity-related conditions. Gradual weight regain is common after lifestyle intervention but can be prevented by continued participation in monthly weight loss maintenance sessions, as well as by high levels of physical activity (ie, 200 to 300 min/wk). Patients unable to reduce satisfactorily with lifestyle intervention may be candidates for pharmacotherapy, recommended as an adjunct. Five medications have been approved by the US Food and Drug Administration for chronic weight management, and each has its own risk/benefit profile. The addition of these medications to lifestyle intervention increases mean weight loss by 2.5 to 8.9 kg compared with placebo. Patients with severe obesity who are unable to reduce successfully with lifestyle intervention and pharmacotherapy are eligible for bariatric surgery, including Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding. The first two procedures yield long-term (≥ 3 years) reductions of ≥ 20% of initial weight that are associated with decreases in morbidity and potentially mortality. Greater resources and dissemination efforts are needed to increase the availability of these three approaches for the millions of Americans who would benefit from them.

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Abstract MP003: Development and Validation of a Prediction Model of Weight Loss Maintenance or Regain at 4 Years in the Look AHEAD Trial

Circulation ◽

10.1161/circ.135.suppl_1.mp003 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Samantha E Berger ◽

Gordon S Huggins ◽

Jeanne M McCaffery ◽

Alice H Lichtenstein

Keyword(s):

Machine Learning ◽

Type 2 Diabetes ◽

Weight Loss ◽

Logistic Regression ◽

Prediction Model ◽

Weight Regain ◽

Initial Weight ◽

Initial Weight Loss ◽

Look Ahead

Introduction: The development of type 2 diabetes is strongly associated with excess weight gain and can often be partially ameliorated or reversed by weight loss. While many lifestyle interventions have resulted in successful weight loss, strategies to maintain the weight loss have been considerably less successful. Prior studies have identified multiple predictors of weight regain, but none have synthesized them into one analytic stream. Methods: We developed a prediction model of 4-year weight regain after a one-year lifestyle-induced weight loss intervention followed by a 3 year maintenance intervention in 1791 overweight or obese adults with type 2 diabetes from the Action for Health in Diabetes (Look AHEAD) trial who lost ≥3% of initial weight by the end of year 1. Weight regain was defined as regaining <50% of the weight lost during the intervention by year 4. Using machine learning we integrated factors from several domains, including demographics, psychosocial metrics, health status and behaviors (e.g. physical activity, self-monitoring, medication use and intervention adherence). We used classification trees and stochastic gradient boosting with 10-fold cross validation to develop and internally validate the prediction model. Results: At the end of four years, 928 individuals maintained ≥50% of their initial weight lost (maintainers), whereas 863 did not met that criterion (regainers). We identified an interaction between age and several variables in the model, as well as percent initial weight loss. Several factors were significant predictors of weight regain based on variable importance plots, regardless of age or initial weight loss, such as insurance status, physical function score, baseline BMI, meal replacement use and minutes of exercise recorded during year 1. We also identified several factors that were significant predictors depending on age group (45-55y/ 56-65y/66-76y) and initial weight loss (lost 3-9% vs. ≥10% of initial weight). When the variables identified from machine learning were added to a logistic regression model stratified by age and initial weight loss groups, the models showed good prediction (3-9% initial weight loss, ages 45-55y (n=293): ROC AUC=0.78; ≥10% initial weight loss, ages 45-55y (n=242): ROC AUC=0.78; (3-9% initial weight loss, ages 56-65y (n=484): ROC AUC=0.70; ≥10% initial weight loss, ages 56-65y (n=455): ROC AUC = 0.74; 3-9% initial weight loss, ages 66-76y (n=150): ROC AUC=0.84; ≥10% initial weight loss, ages 66-76y (n=167): ROC AUC=0.86). Conclusion: The combination of machine learning methodology and logistic regression generates a prediction model that can consider numerous factors simultaneously, can be used to predict weight regain in other populations and can assist in the development of better strategies to prevent post-loss regain.

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The Association Between Rate of Initial Weight Loss and Long-Term Success in Obesity Treatment: Does Slow and Steady Win the Race?

International Journal of Behavioral Medicine ◽

10.1007/s12529-010-9092-y ◽

2010 ◽

Vol 17 (3) ◽

pp. 161-167 ◽

Cited By ~ 96

Author(s):

Lisa M. Nackers ◽

Kathryn M. Ross ◽

Michael G. Perri

Keyword(s):

Weight Loss ◽

Obesity Treatment ◽

Initial Weight ◽

Initial Weight Loss

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Weight Changes after Vertical Banded Gastroplication

Scottish Medical Journal ◽

10.1177/003693300505000206 ◽

2005 ◽

Vol 50 (2) ◽

pp. 58-60

Author(s):

J J Lara ◽

L Murray ◽

R Carter ◽

R Stuart ◽

M E J Lean

Keyword(s):

Weight Loss ◽

Surgical Treatment ◽

Weight Change ◽

Weight Regain ◽

Liquid Diet ◽

Weight Changes ◽

Initial Weight ◽

Initial Weight Loss

Aims: This study assessed the patterns of weight change in response to surgical treatment for obesity. Methods: Vertical Banded Gastroplication (VBG) was performed during the period 1994–2000. Patients were required to follow a liquid diet (8oo kcals) for 12 weeks before surgery. The same diet plus a multivitamin capsule (Forceval) was followed for 12 weeks postoperatively, after which normal foods were introduced. Data from 23 patients, 16 women and 7 men, aged 33–63 years (mean, SD; 42±8yrs), with BMI from 38 to 69 kg/m2 (52.5 ± 8.1 kg/m2) at the time of the surgery were available for analysis. Follow up was 3 to 7 years (mean 4 years). Results: An initial weight loss of 44.4 ± 24.3 kg (min 11.5, max 110.5 kg) was reached during the first two years (mean BMI decrease 15.8 kg/m2). However a regain in weight (36% of the initial weight loss = 5.6 kg/m2) up to 3 to 7 years after surgery was usual. Average annual regain was 13.6 kg (n=17), 9.45 kg (n=11) and 0.8 kg (n=8) during the 3rd, 4th and 5th year after surgery). Five participants reached a BMI below 30 but only one, BMI<25, has maintained all the weight loss after 5 years. Conclusions: Weight loss following VBG ceased after two years with a subsequent substantial weight regain. Auxiliary therapies to counteract weight regain are necessary after VBG.

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A 1000 cc Intragastric Balloon for Weight Reduction

Diagnostic and Therapeutic Endoscopy ◽

10.1155/dte.5.31 ◽

1998 ◽

Vol 5 (1) ◽

pp. 31-35

Author(s):

A. Lavy ◽

J. Lachter ◽

O. Zinder ◽

S. Eidelman

Keyword(s):

Weight Loss ◽

Weight Reduction ◽

Intragastric Balloon ◽

Dietary Therapy ◽

Morbidly Obese ◽

Initial Weight ◽

Initial Weight Loss ◽

Hormone Levels ◽

Preliminary Results ◽

Prolonged Time

Objective: To examine the efficiency of a 1000 cc intragastric balloon as an aid for weight reduction.Subject: Thirty-three morbidly obese persons, after multiple attempts for weight loss.Design: Intragastric 1000 cc balloons were endoscopically inserted into the stomachs of subjects. The balloons were left in place for six months. During that period the patients received dietary therapy. Hormone levels were measured prior to insertion and upon withdrawal of balloons.Results: After a brief initial weight loss, most patients regained the weight initially lost. Mean weight loss after six months was only 8 kg (range 0–22 kg). We found that Bombesin levels, but not Gastrin levels, were significantly lower at the end of therapy than before insertion of the balloon.Conclusion: We conclude that a large intragastric balloon for a prolonged time did not assist in weight loss. Our preliminary results show Bombesin levels change significantly, a finding which warrants further study.

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Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet

Acta Endocrinologica ◽

10.1530/eje-11-0252 ◽

2011 ◽

Vol 165 (2) ◽

pp. 249-254 ◽

Cited By ~ 33

Author(s):

Greeshma K Shetty ◽

Giuseppe Matarese ◽

Faidon Magkos ◽

Hyun-Seuk Moon ◽

Xiaowen Liu ◽

...

Keyword(s):

Weight Loss ◽

Hypocaloric Diet ◽

Short Term ◽

Obese Adults ◽

Neuroendocrine Function ◽

Term Energy ◽

Obese Subjects ◽

Energy Deprivation ◽

To Receive

ObjectiveShort-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic–pituitary–peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified.MethodsIn this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5–38.0 kg/m2) were prescribed a hypocaloric diet (−500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months.ResultsMetreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (P<0.001) and led to the generation of anti-leptin antibodies. Despite free leptin concentration (P for interaction=0.041) increasing from 9±1 ng/ml at baseline to 43±15 and 36±12 ng/ml at 3 and 6 months, respectively, changes in circulating hormones of the thyroid and IGF axes at 3 and 6 months were not significantly different in the placebo- and metreleptin-treated groups.ConclusionsLeptin does not likely mediate changes in neuroendocrine function in response to weight loss induced by a mild hypocaloric diet in overweight and obese subjects.

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The defence of body weight: a physiological basis for weight regain after weight loss

Clinical Science ◽

10.1042/cs20120223 ◽

2012 ◽

Vol 124 (4) ◽

pp. 231-241 ◽

Cited By ~ 131

Author(s):

Priya Sumithran ◽

Joseph Proietto

Keyword(s):

Weight Loss ◽

Body Weight ◽

Energy Expenditure ◽

Weight Regain ◽

Physiological Changes ◽

Initial Weight Loss ◽

Physiological Basis ◽

Subsequent Discussion ◽

Short And Long Term

Although weight loss can usually be achieved by restricting food intake, the majority of dieters regain weight over the long-term. In the hypothalamus, hormonal signals from the gastrointestinal tract, adipose tissue and other peripheral sites are integrated to influence appetite and energy expenditure. Diet-induced weight loss is accompanied by several physiological changes which encourage weight regain, including alterations in energy expenditure, substrate metabolism and hormone pathways involved in appetite regulation, many of which persist beyond the initial weight loss period. Safe effective long-term strategies to overcome these physiological changes are needed to help facilitate maintenance of weight loss. The present review, which focuses on data from human studies, begins with an outline of body weight regulation to provide the context for the subsequent discussion of short- and long-term physiological changes which accompany diet-induced weight loss.

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