1139-OR: Preserved Insulin Secretion Amplifies Metabolic Effects of Visceral Fat

Introduction and Objective: Visceral adipose tissue (VAT) is a key driver of insulin resistance (IR), but it’s unclear if insulin secretory capacity modulates this link. It also remains an open question, if primary hyperinsulinemia—high β-cell output before dysglycemia—is permissive or causal for IR. Since surrogate indices do not allow assessing insulin secretion independently of insulin sensitivity, we used independent tests to examine whether β-cell function (BCF) modifies VAT-associated IR in the German Diabetes Study (GDS). Methods: We analyzed 1,641 GDS participants with normal glucose tolerance (NGT), type 1 (T1D) and type 2 diabetes (T2D), with baseline MRI-measured VAT and subcutaneous adipose tissue (SAT) volumes, clamp-derived insulin sensitivity (M-value), and glucagon-stimulated 6-min C-peptide measurements. Repeated measures were available in 640 participants. Cross-sectional analyses used multivariable linear models with interactions. Longitudinal models predicted M-value change (ΔM) from baseline VAT, ΔVAT, baseline BCF and interactions. Results: In cross-sectional analyses adjusted for sex, BMI and diabetes type, higher VAT was tightly associated with lower M-value (each SD increase in VAT: β=−0.54 SD log-M, p<0.001), whereas SAT was weakly associated with M-value (β=−0.14, p=0.012). Higher BCF associated with higher M-value (β=0.13, p=0.018). However, higher BCF strengthened the inverse VAT association with M-value (VAT×BCF interaction: β=−0.19, p<0.001). The association of VAT with M-value was present in NGT/T2D (ß<-1.22, p<0.001), but weak in T1D (β=−0.57, p=0.054). Longitudinally, increases in VAT related to decreased M-value only in those with higher baseline BCF (ΔVAT×BCF: β=−6.53×10−4, p=0.018). Conclusion: BCF modifies the association of VAT with IR across cross-sectional and longitudinal analyses, indicating that VAT-related IR is strongest with preserved BCF and consistent with insulin hypersecretion contributing to the development of IR. Disclosure K.B. Bódis: Other - travel support; Ended; Sanofi. Other - lecture honoraria; Ended; Pfizer Inc. A. Chadt: None. C. Binsch: None. I. Yurchenko: None. D.M. Mendez Cardenas: None. K. Prystupa: None. F.C. Michelotti: None. K. Pafili: None. S. Trenkamp: None. M. Schön: None. O. Zaharia: None. H. Al-Hasani: None. M. Heni: Advisory Panel; Ended; Chiesi USA, Inc. Speaker's Bureau; Ended; Chiesi USA, Inc. Advisory Panel; Ended; Boehringer Ingelheim International GmbH. Speaker's Bureau; Ended; Boehringer Ingelheim International GmbH, AstraZeneca, Lilly, Novartis AG, Novo Nordisk, Bayer AG. V. Schrauwen-Hinderling: None. M. Roden: Advisory Panel; Current; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Madrigal Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Echosens. R. Wagner: Advisory Panel; Current; Sanofi. Speaker's Bureau; Ended; Daiichi Sankyo, Novo Nordisk.