1296-P: Adipose Tissue Insulin Resistance in RISE: Divergence between Youth and Adults, and Females and Males

Abstract

Adipose tissue insulin resistance (Adipose-IR) is a pathophysiological component of type 2 diabetes (T2D) . We examined:1) Adipose-IR (calculated as fasting insulin x free fatty acids [FFAs]) in youth and adults with impaired glucose tolerance (IGT) or recently diagnosed T2D;2) sexual dimorphism in Adipose-IR in each age group;3) the association of Adipose-IR with β-cell function (βCF) in youth and adults.In RISE, 91 youth [BMI 36.7±24.4 (SD) kg/m2, 59.3% IGT] and 355 adults [BMI 35.1±5.1 kg/m2, 70.7% IGT] had baseline Adipose-IR measured. The relationship of Adipose-IR to hyperglycemic-clamp-derived-βCF and insulin sensitivity (IS) were assessed. Adipose-IR was 2.2-fold higher in youth vs. adults (p<0.001; Fig A) , higher in females than males in both age groups (p<0.05; Fig B) , and higher in T2D vs. IGT in youth (p<0.05; Fig C) . In adults, Adipose-IR correlated positively with all clamp-derived βCF parameters, while in youth it only correlated with steady-state C-peptide. In both age groups, Adipose-IR correlated inversely with clamp-IS. Youth, whether males or females, have 100% higher adipose tissue insulin resistance compared with adults. Moreover, within each age group, females have greater Adipose-IR than males. The higher Adipose-IR in youth vs. adults across a wide range of BMI is suggestive of other yet unknown factors, possibly puberty-related, potentially modulating Adipose-IR. Disclosure S.A.Arslanian: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Other Relationship; AstraZeneca, Research Support; Eli Lilly and Company, Novo Nordisk. T.Consortium: None. S.Caprio: None. K.J.Nadeau: None. K.A.Temple: None. P.Wander: None. M.Cree-green: None. T.S.Hannon: Advisory Panel; Eli Lilly and Company. S.E.Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc. L.El ghormli: None. Funding American Diabetes Association (1-20-RISE-01) ; NIDDK, Department of Veterans Affairs, and Kaiser Permanente Southern California