Chapter 44 Overweight and Obesity
Body Mass Index
Health care professionals define obesity or increased adiposity using the body mass index (BMI), which is an excellent proxy for more direct measurement of body fat. BMI = weight in kg/(height in meters)2. Adults with a BMI ≥30 meet the criterion for obesity, and those with a BMI 25-30 fall in the overweight range. During childhood, levels of body fat change beginning with high adiposity during infancy. Body fat levels decrease for approximately 5.5 yr until the period called adiposity rebound, when body fat is typically at the lowest level. Adiposity then increases until early adulthood (Fig. 44-1). Consequently, obesity and overweight are defined using BMI percentiles; children >2 yr old with a BMI ≥95th percentile meet the criterion for obesity, and those with a BMI between the 85th and 95th percentiles fall in the overweight range. The terminology used for pediatric obesity previously was “overweight” and “risk for overweight.” This terminology has changed to improve consistency with the adult criteria and international definitions of pediatric obesity.
Etiology
Genetics
The rapid rise in obesity prevalence relates to dramatic environmental changes, but genetic determinants may be important for individual susceptibility. Rare single-gene disorders resulting in human obesity are known, including FTO (fat mass and obesity) and INSIG2 (insulin-induced gene 2) mutations as well as leptin deficiency and pro-opiomelanocortin deficiency. In addition, other genetic disorders associated with obesity such as Prader-Willi syndrome have long been recognized (Table 44-1). It is likely that genes are involved in behavioral phenotypes related to appetite regulation and preference for physical activity. More than 600 genes, markers, and chromosomal regions have been associated with human obesity.
DISEASE | SYMPTOMS | LABORATORY |
---|---|---|
ENDOCRINE | ||
Cushing syndrome | Central obesity, hirsutism, moon face, hypertension | Dexamethasone suppression test |
Growth hormone deficiency | Short stature, slow linear growth | Evoked GH response, IGF-1 |
Hyperinsulinism | Nesidioblastosis, pancreatic adenoma, hypoglycemia, Mauriac syndrome | Insulin level |
Hypothyroidism | Short stature, weight gain, fatigue, constipation, cold intolerance, myxedema | TSH, FT4 |
Pseudohypoparathyroidism | Short metacarpals, subcutaneous calcifications, dysmorphic facies, mental retardation, short stature, hypocalcemia, hyperphosphatemia | Urine cAMP after synthetic PTH infusion |
GENETIC | ||
Alstrom syndrome | Cognitive impairment, retinitis pigmentosa, diabetes mellitus, hearing loss, hypogonadism, retinal degeneration | ALMS1 gene |
Bardet-Biedl syndrome | Retinitis pigmentosa, renal abnormalities, polydactyly, hypogonadism | BBS1 gene |
Biemond syndrome | Cognitive impairment, iris coloboma, hypogonadism, polydactyly | |
Carpenter syndrome | Polydactyly, syndactyly, cranial synostosis, mental retardation | Mutations in the RAB23 gene, located on chromosome 6 in humans |
Cohen syndrome | Mid-childhood-onset obesity, short stature, prominent maxillary incisors, hypotonia, mental retardation, microcephaly, decreased visual activity | Mutations in the VPS13B gene (often called the COH1 gene) at locus 8q22 |
Deletion 9q34 | Early-onset obesity, mental retardation, brachycephaly, synophrys, prognathism, behavior and sleep disturbances | Deletion 9q34 |
Down syndrome | Short stature, dysmorphic facies, mental retardation | Trisomy 21 |
ENPP1 gene mutations | Insulin resistance, childhood obesity | Gene mutation on chromosome 6q |
Frohlich syndrome | Hypothalamic tumor | |
Leptin or leptin receptor gene deficiency | Early-onset severe obesity, infertility (hypogonadotropic hypogonadism) | Leptin |
Melanocortin 4 receptor gene mutation |
cAMP, cyclic adenosine monophosphate; FT4, free throxine; GH, growth hormone; IGF, insulin-like growth factor; PTH, parathyroid hormone; TSH, thyroid-stimulating hormone.
Endocrine and Neural Physiology
Monitoring of “stored fuels” and short-term control of food intake (appetite and satiety) occurs through neuroendocrine feedback loops linking adipose tissue, the gastrointestinal (GI) tract, and the central nervous system (Fig. 44-2). GI hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, and vagal neuronal feedback promote satiety. Ghrelin stimulates appetite. Adipose tissue provides feedback regarding energy storage levels to the brain through hormonal release of adiponectin and leptin. These hormones act on the arcuate nucleus in the hypothalamus and on the solitary tract nucleus in the brainstem and in turn activate distinct neuronal networks. Adipocytes secrete adiponectin into the blood, with reduced levels in response to obesity and increased levels in response to fasting. Reduced adiponectin levels are associated with lower insulin sensitivity and adverse cardiovascular outcomes. Leptin is directly involved in satiety, as low leptin levels stimulate food intake and high leptin levels inhibit hunger in animal models and in healthy human volunteers. Adiposity correlates to serum leptin levels among children and adults, with the direction of effect remaining unclear.
Comorbidities
Complications of pediatric obesity occur during childhood and adolescence and persist into adulthood. An important reason to prevent and treat pediatric obesity is the increased risk for morbidity and mortality later in life. The Harvard Growth Study found that boys who were overweight during adolescence were twice as likely to die from cardiovascular disease as those who had normal weight. More immediate comorbidities include type 2 diabetes, hypertension, hyperlipidemia, and nonalcoholic fatty liver disease (Table 44-2). Insulin resistance increases with increasing adiposity and independently affects lipid metabolism and cardiovascular health. Nonalcoholic fatty liver disease occurs in 10-25% of obese adolescents and can progress to cirrhosis.
DISEASE | POSSIBLE SYMPTOMS | LABORATORY CRITERIA |
---|---|---|
CARDIOVASCULAR | ||
Dyslipidemia | HDL <40, LDL >130, total cholesterol >200 | Fasting total cholesterol, HDL, LDL, triglycerides |
Hypertension | SBP >95% for sex, age, height | Serial testing, urinalysis, electrolytes, blood urea nitrogen, creatinine |
ENDOCRINE | ||
Type 2 diabetes mellitus | Acanthosis nigrans, polyuria, polydipsia | Fasting blood glucose >110, hemoglobin, A1c, insulin level, C-peptide, oral glucose tolerance test |
Metabolic syndrome | Central adiposity, insulin resistance, dyslipidemia, hypertension, glucose intolerance | Fasting glucose, LDL and HDL cholesterol |
Polycystic ovary syndrome | Irregular menses, hirsutism, acne, insulin resistance, hyperandrogenemia | Pelvic ultrasound, free testosterone, LH, FSH |
GASTROINTESTINAL | ||
Gallbladder disease | Abdominal pain, vomiting, jaundice | Ultrasound |
Nonalcoholic fatty liver disease (NAFLD) |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CT, computed tomography; FSH, follicle-stimulating hormone; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LH, luteinizing hormone; MRI, magnetic resonance imaging; Peds QL, Pediatric Quality of Life Inventory.