Normal weight metabolically unhealthy phenotype in youth: Do definitions matter?

Background Normal weight metabolically unhealthy (NWMU) adults are at increased risk of cardiometabolic disease, however, little is known regarding NWMU children. Objectives We examined the associations between existing definitions of NWMU in children aged 8 to 10 years and insulin sensitivity (IS) and secretion 2 years later. Methods Data stem from the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort of 630 Caucasian youth, 8 to 10 years old at baseline, with at least one obese biological parent. Of these, 322 normal weight children were classified as NWMU using four definitions. At 10 to 12 years, IS was measured with the Matsuda-insulin sensitivity index; insulin secretion was measured with the ratio of the area under the curve (AUC) of insulin to the AUC of glucose over a 2-hour oral glucose tolerance test. Multiple linear regression models were used. Results Because few children met the existing definitions of metabolic syndrome, associations were examined for less stringent definitions (eg, having two vs no risk factors). At baseline, IS was lower in NWMU children compared to children with no risk factors (virtually all definitions). Moreover, after 2 years, IS was 14.4-19.3% lower in NWMU children with one or more risk factors, and up to 29.7% lower in those with two or more risk factors compared to those with none. Insulin secretion was not predicted by components of the metabolic syndrome. Conclusion Existing definitions of NWMU youth performed relatively similarly in predicting IS as youth entered puberty. Children with one or more components of metabolic syndrome-even when of normal weight-have significantly lower IS over time.