Visual Abstract
HOMA-AD, a surrogate estimate of insulin resistance, has not been comprehensively examined in pediatrics. We investigated: 1) the correlation of HOMA-AD with clamp-measured in vivo insulin sensitivity (IS) in normal-weight (NW) and obese youth spanning from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and 2) the predictive power of HOMA-AD for T2D. Peripheral IS and hepatic IS were assessed with hyperinsulinemic-euglycemic clamps combined with [6,6-2H2]glucose tracer in 357 youth, who also had fasting adiponectin, lipids, and visceral adiposity (VAT) evaluated. HOMA-AD increased from NW to obese and from NGT to IGT to T2D (Table). HOMA-AD correlated inversely with peripheral IS (r=-.84), hepatic IS (r=-.67), HDL (r=-.40), and positively with BMI (r=.64), VAT (r=.62), and triglycerides (r=.43) (all P<0.0001). The area under the curve of receiver operating characteristics for HOMA-AD to distinguish T2D was 0.80 (P<0.0001). In conclusion, a progressive increase in HOMA-AD mirrors the declining IS in youth from NW to obese and from NGT to IGT to T2D. The strong correlations of HOMA-AD with in vivo peripheral and hepatic IS, together with its predictive power (80%) for T2D, support the use of HOMA-AD as a fasting surrogate of insulin resistance in large-scale epidemiological, observational and/or interventional studies in youth.
J. Jacob: None. J. Kim: None. S. A. Arslanian: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Other Relationship; Self; AstraZeneca, Research Support; Self; Eli Lilly and Company, Novo Nordisk.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24-HD01357, R01HD27503); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research Resources (UL1RR024153)
