We demonstrate that in a sample of predominantly Hispanic inner-city high school students, obesity is linked to a host of metabolic abnormalities. As also noted by other investigators,[20
] we found that increasing BMI, was not only related to a larger waist circumference, but associated with increases in blood pressure, abnormalities in the lipid profile, higher fasting insulin levels, and higher levels of CRP. In our sample MetS prevalence also increased with increasing BMI. Healthy weight appeared to be protective of MetS, with only 1 (0.3%) healthy weight adolescent meeting criteria for MetSHOMA
. This is in agreement with Cook and colleagues (2008), who described the prevalence of MetS among normal weight adolescents to be 0-1.6%.[31
MetS is a useful clinical and research construct for identifying Individuals at increased risk of T2DM, CVD, and osteoarthritis,[40
] among other chronic illnesses.[41
] In children, a MetS diagnosis can be a particularly valuable catalyst for an intensive diet and exercise intervention targeted at preventing further disease progression.
However, our work highlights that a definition of MetS, which utilizes IFG, may fail to identify children with significant insulin resistance and hyperinsulinemia. Children can mount compensatory insulin secretion to remain normoglycemic, while displaying evidence of significant insulin resistance, and thus remain at increased risk of developing numerous chronic conditions later in life.[14
] In our sample of over 1,000 adolescents we found marked differences in the prevalence of IFG relative to that of HOMA-IR ≥ 3.99 by BMI percentile categories. IFG was present in only 2.0% of our obese participants. Alternatively, using a conservative HOMA-IR cutpoint of ≥ 3.99 as an estimate of insulin resistance,[22
] 37.8% of our obese adolescents fulfilled this criterion (). The increased prevalence of elevated HOMA-IR scores relative to IFG has been also described by others. For example, Cook et al. analyzing data from 12-19 year olds from NHANES ‘99-‘02, found that 8.6%, 15.4%, and 16.5% of normal, overweight, and obese children respectively had a fasting blood sugar of over 100 mg/dl.[31
] Meanwhile using the data from the same NHANES surveys, Lee reported that roughly 9%, 20% and 60% of normal, overweight, and obese children had a HOMAIR greater than or equal to 3.99.[37
] Using similar data, Li and colleagues found that 13.1% of the population in a nationally representative sample of 12-19 year olds had a fasting glucose above 100 mg/dl, while 37.1% had hyperinsulinemia (fasting insulin above 13.8 μIU/mL).[44
] Although our data are consistent with nationally representative data in demonstrating that elevated HOMA-IR scores and hyperinsulinemia are more common among adolescents than IFG, our point prevalence of IFG is lower than in similar school-based studies as well as nationally representative studies. For the measurement of glucose levels, samples were collected in tubes containing intended to prevent red cells from metabolizing glucose and thus artificially reducing glucose level prior to measurement. Nevertheless, given that there was approximately a 3 hour delay in this study between the blood sample being drawn and the assay being performed, it is possible that our low prevalence of hyperglycemia is the result of a systematic underestimation of glucose values due to our measurement procedure.[45
While MetS components and CRP were significantly associated with both fasting blood glucose and HOMA-IR, they systematically accounted for 2 to 5-fold higher variance in HOMA-IR than in fasting glucose level (). This is likely due to the causal role that has been attributed to both insulin resistance and hyperinsulinemia in the development and progression of hypertension and the dyslipidemic components of MetS. Our work agrees with Sharma and colleagues (2011),[22
] who suggested that the incorporation of HOMA-IR into a pediatric MetS definition creates a more consistent construct that is more likely to reflect a cohesive underlying physiology than a MetS definition that utilizes the IFG adult standard.
Although the average age of our participants was 16.7 ± 1.2 years, we did not ascertain sexual development stage, and there is the possibility that some of our participating students were pre-pubertal. Insulin resistance increases during early teenage years until sexual development Tanner stage 3 and eventually normalizes by the completion of puberty.[2
] However, Lee and colleagues (2006) noted that in a nationally representative sample of US adolescents, HOMA-IR scores demonstrated limited variability by age in normal and overweight adolescents and high variability in obese adolescents.[36
] Moreover, insulin resistance also varies by sex and ethnicity,[48
] therefore future work should determine appropriate age, sex, and ethnicity cut-offs for estimates of insulin resistance.[49
While IFG is a significant risk factor for a host of diseases,[50
] IFG represents an abnormality further along in the progression of obesity to T2DM and likely reflects concurrent insulin resistance and beta cell insufficiency, which occurs after insulin resistance has already been established.[51
] Reduced insulin sensitivity, resulting in compensatory fasting hyperinsulinemia, even in the presence of normal fasting glucose levels, also poses serious health risks and has been implicated in the development of precursors of CVD, T2DM, hypertension, dyslipidemia, hepatic steatosis, polycystic ovary syndrome, and inflammation in the pediatric population.[6
] Given that a primary purpose of the MetS construct is to identify children and youth at risk for diabetes and CVD as early as possible, using a definition of MetS which includes HOMA-IR provides a greater opportunity for interventions intended to halt or reverse progression of MetS to more advanced disease.