Strategies in the Management of Adolescent Obesity

Abstract

Purpose of Review:

We review the current options to manage adolescent obesity which include nutrition, physical activity, behavior modification, sleep management, pharmacotherapy and surgery. Since lifestyle interventions alone are often not effective in adolescents, a multi-disciplinary treatment approach is necessary in management.

Recent Findings:

Medications (often used off-label) and metabolic/bariatric surgery are effective treatment strategies to treat adolescents with severe obesity.

Summary:

The use of pharmacotherapy and surgery is limited due to lack of pediatric obesity tertiary care centers. With more centers, the treatment of adolescent obesity will improve and aid to decrease the prevalence of adult obesity.

Introduction

Adolescence is a pivotal time in human development as a young child transitions to early adulthood [1]. Defined as the period between the ages of 11 and 21, adolescence is marked by puberty—a sequence of physical alterations facilitated by genetic, hormonal and environmental factors [1,2]. Body size, shape and composition change significantly during puberty [3]. For example, females have an increase in body fat, whereas males experience an increase in skeletal muscle mass. These changes are mediated at the hormonal level via gonadotropins, leptin, sex steroids, and growth hormones, including insulin [3]. All adolescents (regardless of weight) have insulin resistance. However, if an adolescent has risk factors for obesity, insulin resistance at onset of puberty may increase the likelihood of obesity being diagnosed. [4,5].

The prevalence of adolescent obesity continues to rise exponentially [5,6]. Obesity currently affects 20.5% of 12 to 19-year-olds in the United States, and 9.5% of adolescents have severe obesity. Obesity disproportionately impacts African American females and Hispanic-American males. There is also a higher prevalence of obesity in adolescents from low-income communities [6].

In the past, treatment of adolescent obesity has focused on lifestyle modification. However, with the growing number of adolescents with severe obesity, pharmacotherapy and/or bariatric surgery are important tools to utilize in select patients [6–8]. This review highlights the current evidence to support the use of nutrition, physical activity, behavior modification with special emphasis on pharmacotherapy and bariatric/metabolic surgery as key components in the treatment of obesity in adolescents.

Diagnosis and Assessment

The use of body mass index (BMI) is the simplest tool to diagnose obesity [9]. Obesity in adolescents is defined as a BMI ≥ 95th percentile for gender/age [6, 8–10]. Obesity is subcategorized into three distinct classes.

• Class I Obesity: BMI at least 95^th percentile – BMI less than 120% of the 95^th percentile or BMI < 35 kg/m², whichever is lower

• Class II Obesity: BMI at least 120% of the 95^th percentile or a BMI at least 35 kg/m², whichever is lower – BMI less than 140% of the 95^th percentile

• Class III Obesity: BMI at least 140% of the 95^th percentile or a BMI at least 40 kg/m², whichever is lower

Severe obesity includes classes II and III obesity [9]. A specific CDC BMI-for-age chart should be used for tracking weight status over time [9].

During the initial assessment, it is important to obtain information on past medical history (including review of medications), dietary history, physical activity assessment, developmental history, sleep history, psychosocial history, family history of obesity and related conditions, and a conduct a review of systems to assess the severity of obesity [7, 9, 10]. A physical exam with measurements of blood pressure and waist circumference, while noting specific features that may suggest a genetic etiology for obesity or specific obesity related condition, is also necessary. (Table 1) (Figure 1)

Table 1:

Key review of systems symptoms, physical exam findings and common genetic syndromes associated with adolescent obesity and related conditions. [10,12]

Review of Systems Symptoms
Symptom	Obesity Related Condition
Nervousness, school avoidance, social inhibitions, sleepiness, wakefulness	Depression, anxiety, bullying
Headaches, visual disturbances, facial numbness	Idiopathic intracranial hypertension (IIH)
Shortness of breath, exercise intolerance	Asthma, lack of physical conditioning
Snoring, daytime somnolence, witnessed apnea, nocturnal enuresis	Obstructive sleep apnea (OSA)
Postprandial abdominal pain (right upper quadrant or epigastric)	Biliary colic/gallstone disease
Indigestion, abdominal pain	Gastroesophageal reflux disease (GERD)
Polydipsia, polyuria, fatigue, nocturia, unexpected weight loss	Type 2 diabetes (T2DM)
Hirsutism, acne, irregular menses	Polycystic ovarian syndrome (PCOS)
Primary amenorrhea	PCOS, Prader-Willi Syndrome
Hip or knee pain	Blount Disease
Dull, aching pain in the hip, thigh, or knee	Slipped capital femoral epiphysis (SCFE), early osteoarthritis, musculoskeletal stress from weight
Fatigue, muscle aches	Vitamin D deficiency

Physical Exam Findings
System	Findings	Possible Causes
Vital Signs	Elevated blood pressure	Hypertension
Skin	Acanthosis nigricans, skin tags	Insulin resistance
	Excessive acne, hirsutism	PCOS
	Violaceous striae	Cushing syndrome
	Deep cysts; inflammatory nodules in axilla/groin	Hidradenitis suppurativa
Eyes	Papilledema, cranial nerve VI paralysis, diplopia	IIH
Throat	Tonsillar hypertrophy	OSA
Neck	Goiter	Hypothyroidism
Chest	Wheezing	Asthma
Abdomen	Tenderness	GERD, gallbladder disease, non-alcoholic fatty liver disease (NAFLD)
	Hepatomegaly	NAFLD
Reproductive	Undescended testes	Prader-Willi Syndrome
Extremities	Abnormal gait, limited hip range of motion	SCFE
	Bowing of tibia	Blount Disease
	Small hands and feet, polydactyly	Some genetic syndromes

Genetic Causes of Obesity and Common Presenting Features
Syndromes
Prader-Willi Syndrome	Hyperphagia, hypogonadism
Bardet-Biedl Syndrome	Retinitis pigmentosa, polydacyly, developmental delay, hypogonadism, renal abnormalities
Fragile X Syndrome	Macro-orchidism, prominent jaw, large ears, developmental delay
Albright Hereditary Osteodystrophy	Short stature, skeletal defects
Alstrom Syndrome	Nystagmus, deafness, blindness, diabetes
Cohen Syndrome	Head/face defects, developmental delay
Monogenetic Etiologies
Congenital Leptin Deficiency	Hypogonadism, hyperphagia, frequent infections
POMC Deficiency	Hypopigmentation, hyperphagia
MC4R Deficiency	Increased linear growth and final height, hyperinsulinism

Suggested approach to management of adolescent obesity.

Laboratory work should include a lipid panel, fasting glucose (or hemoglobin A1c), and aminotransferases to screen for common conditions associated with obesity including dyslipidemia, type 2 diabetes (T2DM), and non-alcoholic fatty liver disease (NAFLD). [11]

Management of Adolescent Obesity

Overview

The staged treatment approach is widely accepted in the management of adolescent obesity. While different components within the approach have evidence to support their clinical use, its use as an entire entity is not validated [12]. The stages of obesity treatment are as follows [9,12]:

• Stage 1 Prevention Plus: lifestyle interventions provided by primary care provider

• Stage 2 Structured Weight Management: monthly visits with a primary care provider and support from registered dietitian

• Stage 3 Comprehensive Multidisciplinary Intervention: intensive weight loss program composed of weekly visits for a minimum of 8–12 weeks at a pediatric weight management center

• Stage 4 Tertiary Care Intervention: use of medical diets, medications, and surgery in addition to Stage 3 interventions

Depending on severity of disease, intensification of efforts is increased and catered to the capacity of the clinical setting and motivation of the family [12]. Key members of a treatment team include a pediatrician trained in obesity medicine, registered dietitian, mental health counselor, coordinator, exercise specialist and in some cases, a bariatric surgeon [7,12].

Nutrition

The basis of all nutrition recommendations include consumption of five or more servings of vegetables and fruits daily, minimizing/eliminating sugar-sweetened beverages, eating breakfast daily, limiting the number of meals eaten outside of the home, limiting portion sizes, and allowing adolescents to regulate their meals without overly restricting food habits [12]. Stage 2 utilizes a daily eating plan with balanced macronutrients per the Dietary Reference Intake (DRI) recommendations and structured daily meals/planned snacks [12]. Once an adolescent receives stage 3 or stage 4 level care, the goal is weight loss. The use of very low energy diets (VLED), revised protein sparing modified fast (rPSMF) or intermittent fasting have recently been studiedin tertiary care centers.

Very low energy diets (VLED), which contain ≤ 800 kcal/day and utilize meal replacements can induce rapid weight loss in adolescents. VLED can also improve insulin sensitivity, glucose levels, HbA1c, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides [13,14]. A 2019 meta-analysis on studies of VLED programs in children and adolescents found that the average weight loss immediately following VLED programs ranged between 4.1 kg at 8 weeks and 30.4 kg at 5 months [13]. Unfortunately, following discontinuation of the VLED, there is significant weight regain. One study recorded weights at follow-up visits without any intervention during the follow-up period, and significant weight regain was noted. Nevertheless, BMI at follow-up was still significantly lower than baseline BMI [13]. VLED is also associated with several side effects including fatigue, hunger, dizziness, and headache [13].

One variant of a VLED is the revised protein sparing modified fast (rPSMF). While a typical protein sparing modified fast consists of 600–1000 kcal daily, a rPSMF allows for a more liberal calorie intake of 1200–1800 kcal daily including 40–60 grams of carbohydrates and 1.2–1.5 grams of protein per kilogram of ideal body weight. One study evaluated rPSMF in adolescents with severe obesity treated at a tertiary care center. The intervention was provided in three phases. During each phase, the recommended carbohydrate consumption was gradually increased from 40 grams to 100–200 grams daily (at 12 months). While adherence diminished significantly, rPSMF led to clinically significant weight loss. The mean weight change was −1.3 ± 10.6 kg (range −17.7 kg to 14.8 kg). Adolescents also reported significant improvement in physical and psychosocial quality of life [14].

Intermittent fasting is another nutrition intervention for treatment of obesity [15]. In a recent study, intermittent fasting was shown to be feasible, effective and accepted by adolescents with obesity [15]. In this study, adolescents aged 12–17 years were assigned to 3 days of VLED and 4 days of an individualized healthy eating plan for 13 weeks, followed by 13 weeks in which they chose the number of VLED versus individualized healthy eating plan days per week [15]. Significant decreases were observed in BMI z-score, waist-to-height ratio, and body fat percentage [15]. Furthermore, improvements in emotional eating and emotional/social wellbeing were noted. All participants reported recommending this diet to other youth, and a majority of the participants felt that they could continue the diet for 6, 12, or 18 months [15]. Common side effects of VLED include fatigue, hunger, postural dizziness, nausea, muscle cramps, headache and bad breathe. A recent meta-analysis reviewing utility of VLED in children and adolescents showed very minimal psychological risks but further studies need to assess impact on quality of life and role of VLED on disordered eating [16] Similar findings were found when intermittent fasting was compared to continuous energy restriction [17].

Physical Activity

Adolescent obesity is closely tied to decreased physical activity and significant sedentary behavior. It is widely accepted in adult literature that physical activity contributes mainly to weight maintenance, it is important in both the prevention and treatment of adolescent obesity [18, 19]. Studies have demonstrated physical activity, especially in the context of family-based therapy for the treatment of obesity, are beneficial and also promote additional health benefits including improving insulin sensitivity, blood pressure and cholesterol [1,20].

National guidelines recommend adolescents participate in at least 60 minutes of moderate to vigorous intensity physical activity daily [21]. The latest studies show that only 20 percent of adolescents report sufficient activity to meet the relevant aerobic and muscle-strengthening guidelines [8]. Adolescents with obesity struggle with meeting the recommendations due to negative peer experiences with exercise and reduced exercise tolerance [8]. As a result of increased physical activity, adolescents may spend less time playing computer games, watching TV, or exploring the Internet. Adolescents should spend no more than 2 hours per day on non-educational media. [8,9,12]

Behavior Interventions

Family-based intervention (FBT) is the first line treatment of obesity for children [23]. FBT targets both children and parents/caregiver, and the main components of FBT include dietary modification and energy expenditure modification via goal setting, self-monitoring, reward systems and stimulus control. FBT has been shown to promote clinically meaningful weight loss in children [23]. An examination of twenty-five years of FBT studies revealed that at 6 months after starting treatment, 80–85% of children had BMI z-score changes ≥ 0.5, with 67% of children maintaining BMI z-score changes ≥ 0.5 at 10 years [23]. To date, there are limited studies illustrating the same success within adolescent populations.

Motivational interviewing (MV), an extension of FBT, is an alternative intervention for obesity treatment and prevention. MV uses a directive person-centered approach designed to explore ambivalence and activate motivation for change [24]. A guiding communication style invites adolescents to consider their own situation and find solutions to those situations. This approach is especially helpful to elicit change behavior. Studies have shown that motivational interviewing combined with other forms of therapy have been proven to be effective in treatment of adolescent obesity [24].

Mindfulness is gaining popularity as a treatment option for obesity in adults. Defined as “the awareness that arises from paying attention on purpose, in the present moment and nonjudgmentally,” mindfulness-based interventions are effective in improving binge eating, emotional eating and external eating behavior [25]. One study evaluated the utility of mindful eating interventions (MEI) in adolescents with severe obesity [25]. While MEI was not effective in decreasing BMI or BMI z-score, the intervention was only 6 hours over a period of six months [25].

Acceptance and commitment therapy (ACT) is another psychological treatment found to promote weight loss in adults when combined with lifestyle modification. ACT was recently tested in adolescents over a 16-week period. While there were only six adolescents who completed treatment, there was a reported increase in cognitive restraint, reduction in hunger and a small increase in physical activity [26].

More studies of greater intensity and larger sample size are needed to assess the efficacy of MEI and ACT as behavioral based treatment options to address obesity in adolescents.

Sleep Management

Shorter sleep duration is associated with up to an 80% increase likelihood of obesity [27]. National guidelines suggest that optimal sleep duration for adolescents is 8 to 10 hours [28] However, a recent poll completed by the National Sleep Foundation: Sleep in America poll found that 16% of sixth graders get less than 8 hours of sleep per night, and only 75% of 12^th graders get sufficient sleep [29]. Interventions addressing sleep in adults have resulted in improved weight and body composition [8]. There is minimal evidence to support the role of sleep optimization asa treatment for adolescent obesity. Nevertheless, initiating an earlier bedtime, removal of electronic screens from the bedroom and creation of family rules regarding screen use prior to bed can aid in improving sleep duration and in turn promote weight loss [8].

Pharmacotherapy

Use of pharmacotherapy is a key component of adolescent obesity treatment in a tertiary care center. Because only 2–15% of adolescents with severe obesity respond to intensive lifestyle intervention, the use of anti-obesity medications (AOMs) is necessary to treat severe obesity [7]. Initiation of pharmacotherapy should be considered for BMI ≥95^th percentile (or BMI ≥30 kg/m²) with comorbidity or BMI ≥120% of 95^th percentile (or BMI>35 kg/m²) without comorbidity. Medication should be continued if ≥ 5% BMI reduction from baseline at 12 weeks [7].

There are two FDA approved AOMs for use in the adolescent population: orlistat and phentermine.

Orlistat

Orlistat is approved for treatment of obesity in adolescents ages 12 years or older [30]. It is a reversible inhibitor of lipase, preventing hydrolysis of triglycerides into free fatty acids causing fecal fat excretion and a caloric deficit [30]. The largest orlistat trial showed safety at one year with about a quarter losing ≥5 % BMI [31, 32]. Due to common side effects of oily stools and spotting, use of orlistat is limited [30].

Phentermine

Phentermine is indicated in ages 16 years or older with BMI ≥30 or ≥27 in presence of comorbidity [33]. Phentermine is a sympathomimetic amine that suppresses appetite. A twelve-week trial showed phentermine was well-tolerated in the pediatric population with no change in baseline systolic or diastolic blood pressure [34]. No long-term safety data is available for this population.

The following medications are FDA approved for non-obesity indications in the adolescent population. When prescribing these medications, it is recommended that a standard informed consent is completed in the medical record documenting the following [7]:

• conversation about off-label drug use

• patient/family member understand risks/benefits

• description of potential major and minor side effects are reviewed

• confirmation of the absence of contraindications to the drug

• appropriate follow up care was advised

• the patient/family member understands how to reach prescribing provider if any questions or concerns arise

• advise urgent medical attention for emergencies, including suicidal ideation and worsening depression

Liraglutide

Liraglutide is FDA approved for the treatment of T2DM in ages 10 and older [35]. It is a glucagon-like peptide-1 (GLP-1) receptor agonist that delays gastric emptying and lowers blood glucose [35]. Several small studies have shown safety with liraglutide 3 mg/day in children and adolescents with mild GI side effects [36–38]. A 56-week double blind randomized control trial in pubertal adolescents has been completed; results are pending [39].

Exenatide

Exenatide is indicated for the treatment of T2DM in ages 16 and older [40]. It is a GLP-1 receptor agonist [40]. Prior studies of adolescents with obesity confirmed safety and BMI reduction [41]. In Prader-Willi Syndrome, there are improvements in appetite without weight change [42]. There is a clinical trial currently recruiting patients for weekly dosing of exenatide to treat adolescents with severe obesity [43].

Metformin

Metformin is indicated for the treatment of T2DM in ages 10 and older [44]. It is a biguanide that decreases hepatic glucose synthesis and increases insulin sensitivity [44]. Past studies have shown variable effects of metformin on BMI in non-diabetic children and adolescents depending on dose and length of treatment. Metformin is mainly effective short-term [45–49]. There is a more consistent reduction in BMI in antipsychotic-related weight gain and obesity in children and adolescents with insulin resistance [50–52, 58].

Topiramate

Topiramate is approved for treatment of seizure disorder in ages 2 and older and migraine prophylaxis in ages 12 and older [53]. The mechanism for weight loss is not fully understood. Cognitive impairment is the limiting side effect with treatment [54]. Rare but unique to the pediatric population is oligohidrosis (decreased sweating with subsequent hyperthermia) [53]. Topiramate is effective in reducing weight in children and adolescents with obesity and treating weight gain associated with anti-psychotic use [54–58]. Topiramate may also be helpful in treating Prader Willi [61].

Zonisamide

Zonisamide is similar to topiramate but not as well tolerated. It is approved to treat partial seizures in ages 16 and older [62]. The exact mechanism is unknown but may involve blockage of sodium and calcium channels and inhibition of carbonic anhydrase. Zonisamide has been shown to decrease weight [60, 63] One trial of children ages 6–18 showed about 30% of patients on zonisamide experienced a ≥5% weight loss [63]

Bupropion Hydrochloride

Bupropion hydrochloride is approved for treatment of depression and attention deficit hyperactivity disorder (ADHD) in ages 6 and older and smoking cessation for ages 14 and older [64]. Bupropion works by inhibiting neuronal uptake of norepinephrine and dopamine [64]. The only trial specifically evaluating weight loss in the pediatric population showed reduction in BMI at 6 weeks in adolescent smokers on bupropion, but this was not sustained at 6 months [65].

Lisdexamphetamine

Lisdexamphetamine is approved for treatment of ADHD in ages 6 and older [66]. It is a sympathomimetic with CNS stimulant activity [67]. Growth should be monitored as stimulants can slow growth rate in the pediatric population in a dose dependent fashion [67]. Although not indicated for binge eating disorder (BED) in adolescents up to age 18 years old, lisdexamfetamine has been shown to improve BED symptoms without a change in BMI [68].

Setmelanotide

Setmelanotide, a selective agonist of melanocortin-4 receptor, is pending FDA approval of use in children and adolescents [69]. Administered via a daily subcutaneous injection, there is one case study showing improvement of hunger and in weight in a patient with LEPR deficiency [70]. Multiple studies are evaluating the use of setmelanotide in treatment of rare genetic causes of obesity including POMC deficiency, LEPR deficiency, Bardet-Biedl syndrome, and Alstrom syndrome [71–75].

Phentermine-Topiramate, Locasarin and Bupropion-Naltrexone are FDA approved medications for the treatment of overweight (BMI 27 ≥ kg/m²) with 1 comorbidity or obesity (BMI ≥ 30 kg/m²) in patients 18 years and older [7]. The use of these medications in adolescents younger than 18 years is off-label and should be appropriately documented in the patient’s medical record, as discussed above [7]. There are some pending clinical trials assessing the safety and efficacy of these medications in adolescents with severe obesity [76,77]

Metabolic and Bariatric Surgery (MBS)

MBS can be considered in adolescents with Class II obesity and significant co-morbidities including severe obstructive sleep apnea, T2DM, idiopathic intracranial hypertension, non-alcoholic steatohepatitis, Blount’s disease, SCFE, GERD or hypertension or Class III obesity. Surgery is not limited based on bone age or Tanner stage. Patients with medically correctable causes of obesity, ongoing substance abuse, any medical, psychiatric or cognitive condition that prevents adherence to post-operative regimen and current or upcoming pregnancies are not candidates for MBS. There are several MBS options available including laparoscopic adjustable gastric band (LAGB), vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and bilopancreatic diversion (BPD) with or without duodenal switch [78].

Laparoscopic adjustable gastric band (LAGB)

The LAGB limits food intake with the use of an adjustable, banded balloon that restricts food intake at the level of the gastroesophageal junction [79]. Since the band is adjustable, the surgical procedure is reversible. LAGB was recently evaluated in adolescents with severe obesity. Less than 20% of the patients lost > 50% of excess weight with close to 50% of patients requiring additional surgery [80]. LAGB is also associated with a high complication and explant risk [81]. For these reasons, LAGB is not an ideal option for treatment of adolescent obesity.

Vertical sleeve gastrectomy (VSG)

VSG, the most common procedure in adults, removes 80% of the stomach creating a sleeve volume of 60–100 mill-liters [79]. In a multicenter, prospective study looking at three-year follow-up of weight loss in adolescent undergoing sleeve gastrectomy, the mean percent weight loss following sleeve gastrectomy was 26% [82].

Roux-en-Y gastric bypass (RYGB)

RYGB is the best-studied MBS type in adolescents with long-term follow-up studies demonstrating promising outcomes. This surgery creates a smaller gastric pouch with accelerated flow to the jejunum, bypassing the remaining stomach and duodenum. The FABS-5+ study is a prospective clinical trial that demonstrated excellent sustained BMI reduction in participants up to 12 years following the procedure with improved obesity-related diseases [83].

Bilopancreatic diversion (BPD)

BPD promotes the most weight loss and remission of co-morbidities in the adult population. However, its use in adolescents is limited because of the high risk of protein malnutrition and vitamin deficiencies. There is a need for more studies to evaluate the safety and efficacy in adolescents with severe obesity. A VSG can be revised to a BPD with duodenal switch or single anastomosis duodenal switch once an adolescent reaches adulthood [78].

Endoscopic bariatric therapies (EBT)

EBT is an emerging class of weight loss interventions that manipulates the stomach, altering volume and/or gastric emptying [78]. There are four EBT approved by the FDA for use in adults including intragastric balloons, vagal stimulator and gastric aspiration devices. Like LAGB, the use of EBT is adjustable and reversible. EBT can also serve as a bridge to MBS or aid in weight loss when surgery is contraindicated [84]. However, weight loss in comparison to traditional MBS procedures is suboptimal. Additionally, the role of EBT in treatment of adolescent obesity is unknown at this time.

Conclusions

The treatment of adolescent obesity has traditionally focused on lifestyle modifications. While dietary change and increased physical activity are effective in school aged children, the prevalence of adolescent obesity continues to rise. Adolescents require additional treatment options to manage obesity. Preliminary research show pharmacotherapy and surgery are effective tools to consider in select patients. Nevertheless, these therapies are under-utilized due to limited clinical data to support safety and efficacy and lack of access to tertiary care centers. With over half of American adults expected to have obesity within the next ten years, increasing the number of options to manage adolescent obesity is essential to treat the epidemic.