Adolescent Obesity and Its Risks: How to Screen and When to Refer

• What laboratory evaluation is warranted and practical in the office setting?

Laboratory evaluation is warranted when obesity or risk factors for comorbidities of obesity are present. At minimum, this should include lipid screening, liver enzymes (ALT and AST), and fasting glucose as outlined above. This approach, however, fails to identify all individuals with obesity-associated comorbidities. ALT is only moderately sensitive in detecting NAFLD [51], and fasting glucose levels only become abnormal when compensation for the degree of insulin resistance is inadequate to maintain normal fasting glucose homeostasis. As a result, while abnormal results on screening are suggestive of disease, normal results do not necessarily confer its absence. Thus, for high-risk subjects, additional testing and/or referral should be considered.

The hyperinsulinemic euglycemic clamp is the “gold standard” for measuring insulin sensitivity, but it is labor intensive and impractical in routine clinical settings. Alter-native approaches using surrogate markers have commonly been utilized, including fasting insulin and glucose levels and 2-hour oral glucose tolerance test (OGTT). The utility of these approaches in the clinical setting has been limited by several factors, including lack of a universal insulin assay. However, despite these limitations, obtaining fasting insulin in addition to fasting glucose or performing 2-hour OGTT can be useful in providing crude estimates of insulin resistance in certain high-risk subpopulations [52,53]. Recently, the ADA added HgA1C measurement as diagnostic criteria for pre-diabetes (5.7%–6.4%) and diabetes (> 6.5%) [54]. Benefits of HgA1C measurement include reliable measurements in nonfasting conditions and reflection of glucose over time. Studies in pediatric patients have shown the usefulness of HgA1C as a measure of future glucose intolerance or diabetes [55]. When fasting insulin or HgA1C are elevated and/or OGTT is abnormal, this suggests the presence of insulin resistance and need for intervention.

Proposed guideline criteria for the diagnosis of “metabolic syndrome” in adolescents include the following: (1) glucose intolerance, (2) elevated waist circumference or BMI, (3) hypertriglyceridemia, (4) low HDL, and 5) hypertension. There is no universal definition for metabolic syndrome in childhood and adolescence, and cut-off values in each category vary by study group [41–43,56]. When insulin resistance is present, it should alert the clinician to the increased likelihood for metabolic syndrome and NAFLD, and additional screening should be performed accordingly. NAFLD is present in about 25% of all overweight children and is strongly associated with insulin resistance and the metabolic syndrome [57]. Hispanic patients have an increased prevalence of NAFLD compared with patients of other ethnicities [58,59]. Elevated liver transaminases (AST and ALT) are commonly used to screen for NAFLD. However, since these markers are indicative of hepatocellular damage, they may remain within normal limits and correlate poorly with early steatosis [51]. Alternative approaches have been proposed in high-risk populations to detect early steatosis and improve long-term prognosis [60].

Case Continued

The patient underwent laboratory assessment that included fasting glucose and insulin, fasting lipid panel, and ALT. Results were suggestive of insulin resistance and metabolic syndrome and included the following: fasting glucose 108 mg/dL, fasting insulin 65 uIU/mL (reference range 3–25), HgA1C 5.9% (reference range 4.2–5.8), total cholesterol 178 mg/dL, HDL cholesterol 35 mg/dL, LDL cholesterol 110 mg/dL, triglycerides 157 mg/dL, and ALT 40 u/L. Blood pressure, as noted above, is at the 95th percentile for age and height.