Obesity

As of 2020, the estimated prevalence of pediatric obesity in the United States is 10%-15% in young children (ages 2 to 5 years) and 20% in adolescents. Obesity prevalence differs by race, ethnicity, and socioeconomic status, with higher prevalence in those with lower socioeconomic status.

• Most pediatric obesity is “exogenous,” due to energy imbalance (caloric intake exceeds energy expenditure). Children with obesity are not routinely screened for syndromic and hormonal causes of obesity but should be screened if there are other suggestive signs or symptoms.

• Children with obesity who are relatively tall are more likely to have exogenous obesity, whereas a genetic or endocrine cause should be considered in children with obesity who have short stature.

• Obesity in children is associated with increased blood pressure, decreased high-density lipoprotein (HDL) cholesterol levels, increased triglyceride levels, insulin resistance, and increased risk of nonalcoholic fatty liver disease.

• Obesity in childhood tracks strongly into adulthood, at which point it is associated with an increased risk of cardiovascular disease, dyslipidemia, hypertension, diabetes, and other comorbidities.

Physical Exam

• Assess for relevant dysmorphic features, such as small ears and hands (Prader-Willi syndrome), polydactyly or bifid uvula (Bardet-Biedl syndrome), or short fourth metacarpal (pseudohypoparathyroidism type 1A).

• Check the back and front of the neck and axillae for acanthosis nigricans (see figure below). If the acanthosis has an odd appearance, use an alcohol swab to ensure that it is truly hyperpigmentation (i.e., does not wash off).

• Striae that are thin and skin-colored are common in obesity, whereas thicker violaceous striae raises suspicion for Cushing syndrome/disease.

• Perform a pubertal exam and, in males, a careful testicular exam to assess for lack of pubertal progression and/or undescended testes, which may suggest Prader-Willi syndrome, Bardet-Biedl syndrome, or (rarely) leptin deficiency or leptin receptor mutations.

Classification

Screening

Metabolic complications: Annual blood pressure screening is warranted, along with screening for diabetes and dyslipidemia as described below. Blood tests for alanine aminotransferase (ALT) and aspartate transaminase (AST) may also be measured to screen for the possibility of fatty liver, although currently no clear consensus exists regarding frequency or utility of such screening.

Dyslipidemia: The National Heart, Lung, and Blood Institute (NHLBI) 2011 guidelines recommend universal screening for dyslipidemia before puberty (ages 9-11 years) and after the completion of puberty (ages 17-21 years). In addition, the NHLBI recommends screening with a fasting lipid panel periodically for children with BMI ≥95th percentile (i.e., children with obesity).

Diabetes: Screening can be performed with a fasting glucose, 2-hour oral glucose-tolerance test (OGTT; involves checking glucose 2 hours after consuming a 75-g glucose drink), or hemoglobin A1c (HbA1c). The latter is typically most convenient, although some controversy exists about its application as a diagnostic tool in children. Fasting insulin levels are not of diagnostic value and should not be ordered. See the Diabetes section for a table of diagnostic values for diabetes and “prediabetes” and the ADA Recommendations for Screening and Diagnosis of Type 2 Diabetes in Children and Adolescents for guidelines on glycemia screening in youth with obesity.

Etiology: Routine screening for underlying medical causes is not warranted in children with obesity who have normal-to-tall stature and no syndromic features. For children with obesity and short stature and/or syndromic features, screening for an underlying abnormality is important to consider.

• Thyroid screening (thyroid-stimulating hormone [TSH] and free thyroxine [T4], or TSH with “reflex” additional testing if TSH is abnormal) is relatively straightforward, but hypothyroidism is rarely a cause of obesity. More commonly, mildly elevated TSH with normal free T4 will be detected secondary to obesity. This mild TSH elevation is a reversible abnormality associated with obesity and does not require treatment.

• Cushing syndrome is rare, and routine screening is not indicated unless other suggestive features are present.

• Growth hormone deficiency is also rare, and screening is not indicated unless growth velocity is compromised.

• Genetic or syndromic screening should be guided by other clinical features.

Metabolic Complications

Cardiovascular risk: “Metabolic syndrome” is defined in adults as a constellation of at least three of the five cardiovascular risk factors listed below. However, the utility of this concept as a diagnostic tool in children is unclear. Some studies have shown that the features of this diagnosis are not stable throughout the physiological changes that occur in puberty. For this reason, the authors of this rotation guide do not favor the use of the term “metabolic syndrome” in children. Nonetheless, recognition of cardiovascular risk factors is important in the pediatric population.

The following five risk factors are used to assess metabolic syndrome (three or more factors indicate presence of metabolic syndrome):

• increased waist circumference

• increased blood pressure

• increased triglycerides

• decreased HDL cholesterol

• elevated blood sugar

Glucose homeostasis: The normal physiology of puberty includes an increase in insulin resistance, peaking in mid-to-late puberty, and decreasing when pubertal development is complete. This is related, at least in part, to an increase in growth hormone (GH) levels during mid-to-late puberty. For this reason, acanthosis nigricans and hyperinsulinemia may occur during puberty and improve after pubertal development is complete.

• An important principle of glucose homeostasis is that insulin resistance and hyperinsulinemia are not, by themselves, the cause of diabetes. Type 2 diabetes only occurs when the pancreas fails to compensate for insulin resistance with increased insulin secretion. Thus, patients with signs of insulin resistance or labs consistent with hyperinsulinemia should be counseled about diabetes risk and screened for diabetes, but most of these patients will not develop diabetes in childhood.

Acanthosis nigricans: Acanthosis nigricans is thickening and hyperpigmentation of skin around the neck and in areas of increased friction (see image below), such as the axillae, and indicates hyperinsulinemia. Mild acanthosis is typically found only at the posterior neck, whereas more severe acanthosis extends to the side and anterior neck. Acanthosis nigricans typically indicates insulin resistance and resulting hyperinsulinemia, but most patients with acanthosis nigricans do not have diabetes.

Acanthosis Nigricans

Dysglycemia: Youth diagnosed with type 2 diabetes should receive treatment as described in the Diabetes section. Patients with prediabetes based on HbA1c (5.7%-6.4%), fasting glucose (100-125 mg/dL), or 2-hour glucose following oral glucose-tolerance testing (140-199 mg/dL) should be counseled regarding improved nutrition and increased activity. Referral to a multidisciplinary weight-management program should be considered, especially for those with severe obesity.

• Treatment:

  • Metformin is an oral pharmacologic therapy that may be considered for treatment of prediabetes in adolescents with obesity. However, its use for this indication is controversial and not approved by the FDA. Studies have demonstrated that metformin treatment in adolescents is associated with modest beneficial effects on BMI and measures of insulin resistance. The Diabetes Prevention Program Outcomes Study demonstrated that metformin therapy delayed onset of type 2 diabetes in at-risk adults. However, a recent study (RISE) in 91 children and adolescents with obesity (age range, 10-19 years) suggested that metformin did not have similar efficacy in delaying progression of type 2 diabetes in youth, reporting no significant differences between metformin and placebo groups in beta-cell function following treatment.

  • Liraglutide and semaglutide are glucagon-like peptide 1 receptor agonists that are FDA-approved for use in children aged ≥12 years for the indication of chronic weight management. Studies have shown that liraglutide and semaglutide lead to weight loss in adolescents; however, their use may be limited by the need for subcutaneous injections and the gastrointestinal adverse effects.

Dyslipidemia: The normal physiology of puberty includes a decrease in low-density lipoprotein (LDL) cholesterol. The 2011 NHLBI recommendations suggest performing universal screening for dyslipidemia before puberty (ages 9-11 years) and after the completion of puberty (ages 17-21 years). (A 2016 statement by the United States Preventive Services Task Force found inadequate evidence to support this recommendation.) In addition to universal screening, the 2011 NHLBI recommendations suggest screening with a fasting lipid panel periodically for children with BMI ≥95th percentile (i.e., children with obesity).

Triglyceride and LDL cholesterol levels change in relation to the timing of meals. Serum triglyceride levels are highest in the 2 hours after eating and subsequently decline as time of fasting increases. LDL cholesterol, in contrast, tends to increase modestly with increasing time of fast. HDL cholesterol and non-HDL cholesterol (total cholesterol minus HDL cholesterol) levels do not change substantially with meals. Thus:

• Nonfasting non-HDL cholesterol levels can be used for screening.

• Normal triglyceride levels on a nonfasting sample confirm normal triglyceride, whereas elevated triglyceride on a nonfasting sample requires confirmation with a fasting sample.

• Although elevated LDL cholesterol on a nonfasting sample likely implies elevated LDL cholesterol on a fasting sample, a fasting lipid sample is recommended before making any treatment decisions related to high LDL cholesterol.

  • Treatment: The most common pattern of dyslipidemia seen in children with obesity is an elevation in triglycerides and a reduction in HDL cholesterol. This pattern should prompt counseling about future cardiovascular risk as well as recommendations for dietary modification and increased physical activity as outlined in the NHLBI 2011 guidelines. Pharmacologic treatment is not warranted for children with low HDL cholesterol and/or mild-to-moderate elevations in triglycerides. Children with fasting triglycerides ≥500 mg/dL confirmed on repeat testing can be referred to cardiology for consideration of treatment. NHLBI guidelines for treatment of elevated LDL cholesterol in children and adolescents are as follows:

  • If the average of two fasting LDL cholesterol values is ≥250 mg/dL, children should be referred directly to a lipid specialist.

  • If the average of two fasting LDL cholesterol values is ≥190 mg/dL after a 6-month trial of lifestyle modification, consider statin treatment in those aged ≥10 years regardless of risk factors.

  • If the average of two fasting LDL cholesterol values is <130 mg/dL, statin treatment is not indicated.

  • If the average of two fasting LDL cholesterol values is 130-190 mg/dL, recommendations for statin therapy depend on family history and individual risk factors as described in the guidelines.