Visual Abstract
Simple metabolic indices are necessary in large-scale epidemiological studies to follow β-cell function (βCF) in obese youth at risk for type 2 diabetes (T2D). Using a math model (AJP Endo 2020) of insulin sensitivity (IS) and βCF from an oral glucose tolerance test (OGTT) we aimed to: a) validate mDI against euglycemic-hyperinsulinemic and hyperglycemic clamps in obese youth with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and T2D (age 15.1±1.8 yrs; BMI 36.2±6.0 kg/m2), and b) compare mDI estimated without insulin (mDI w/o I) against mDI with insulin and oral DI (oDI; insulinogenic index/fasting insulin) for predicting dysglycemia. Model-derived parameters correlated with clamp-derived ones: model vs. clamp IS (R2=0.47), model-βCF vs. clamp 1st and 2nd-phase insulin secretion (R2=0.65, R2=0.66), and mDI vs. clamp-derived DI (cDI) (R2=0.56, all P<0.001). mDI w/o I correlated with mDI with insulin (R2=0.91), cDI (R2=0.54), and oDI (R2=0.57, all P<0.001). mDI w/o I correlated strongly with OGTT glucose area under the curve (G-AUC) (Fig. A). mDI w/o I was markedly reduced in IGT (68%) vs. NGT youth, while oDI was reduced by only 29%, and cDI by 27%. mDI w/o I was superior to oDI in detecting IGT (Fig. B) and comparable to oDI in detecting T2D (Fig. C). Because mDI w/o I is more sensitive than oDI in detecting dysglycemia and does not need insulin, it is a cost effective surrogate of βCF applicable to large-scale studies.
J. Ha: None. J. Kim: None. A. Sherman: 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.
