This issue highlights Pediatric Endocrine Self Assessment Program. Test your clinical knowledge and prepare for your exam. Available on the online store.
In clinic you are seeing a 14-year-old African American boy who is obese (BMI = 31 kg/m2). He has a family history of type 2 diabetes mellitus in his father and maternal grandfather. On physical examination, you note central obesity and marked acanthosis nigricans. His fasting blood glucose concentration is 101 mg/dL (5.61 mmol/L) (reference range, 70-110 mg/dL [3.88-6.11 mmol/L]), and his blood pressure is 134/86 mm Hg.
Which of the following findings is the greatest predictor of insulin resistance in this child?
- Normal insulin concentration
- Elevated LDL-cholesterol concentration
- Elevated triglyceride concentration
- Elevated small, dense LDL particle number
- Elevated HDL-cholesterol concentration
Elevated small, dense LDL particle number
The metabolic syndrome is a cluster of cardiovascular risk factors including central obesity, high blood pressure, elevated triglycerides, low HDL cholesterol (thus, Answer E is incorrect), and elevated fasting glucose. In pediatric patients, the metabolic syndrome is most often diagnosed according to criteria that are adapted from adult criteria, such as those developed by the National Cholesterol Education Program. The most commonly used criteria specify cutoff values for measurements of fasting blood glucose (typically >100 mg/dL [>5.5 mmol/L]); HDL cholesterol (<50 mg/dL [<1.30 mmol/L]); triglycerides (>110 mg/dL [>1.24 mmol/L]); blood pressure above the 90th percentile for sex, age, and height; and waist circumference above the 90th percentile for age and sex. To be classified as having the metabolic syndrome, an adolescent must have abnormal values for 3 of these 5 components. The metabolic syndrome is linked to insulin resistance (thus, Answer A is incorrect) and visceral obesity and is associated with underlying abnormalities in cellular function, including increased inflammatory signaling, oxidative stress, and dysfunction of mitochondria and the endoplasmic reticulum. The presence of the metabolic syndrome in childhood has been linked to increased risk of developing type 2 diabetes mellitus in adulthood. African American patients appear to manifest the metabolic syndrome differently than white and Hispanic patients. Black patients with metabolic syndrome are much less likely to exhibit elevated triglycerides. In a survey of 2456 adolescents, Johnson et al documented that although 26% to 32% of white and Hispanic adolescents had triglyceride concentrations above 110 mg/dL (>1.24 mmol/L), only 10% of black adolescents exhibited triglyceride elevations, potentially because of lower levels of lipoprotein lipase (thus, Answer C is incorrect). LDL-cholesterol elevations (Answer B) are not significantly associated with metabolic syndrome. However, elevations in small, dense LDL particle number (Answer D) are seen in this syndrome, including in persons of African American descent. These small, dense LDL particles are linked to increased risk of coronary artery disease, possibly because small, dense LDL particles have increased access to the subendothelial space, increased susceptibility to oxidation, and increased uptake by macrophages. LDL electrophoresis is used to measure small, dense LDL particle number and the results are reported in milligrams per deciliter of small, dense particles, which comprise 12% to 25% of the total LDL. The mainstay of treatment for the metabolic syndrome and related abnormalities is lifestyle modification with increased physical activity and decreased caloric intake.
List the lipid characteristics associated with the metabolic syndrome and explain some of the differences observed in the manifestation of this syndrome in various ethnic groups.
Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2010;375(9710):181-183.
Johnson WD, Kroon JJ, Greenway FL, Bouchard C, Ryan D, Katzmarzyk PT. Prevalence of risk factors for metabolic syndrome in adolescents: National Health and Nutrition Examination Survey (NHANES), 2001-2006. Arch Pediatr Adolesc Med. 2009;163(4):371-377.
Sumner AE. Ethnic differences in triglyceride levels and high-density lipoprotein lead to underdiagnosis of the metabolic syndrome in black children and adults. J Pediatr. 2009;155(3):S7.e7-e11.
Walker SE, Gurka MJ, Oliver MN, Johns DW, DeBoer MD. Racial/ethnic discrepancies in the metabolic syndrome begin in childhood and persist after adjustment for environmental factors. Nutr Metab Cardiovasc Dis. 2012;22(2):141-148.