893-P: Triglyceride-Rich Remnant Lipoproteins, Insulin Resistance, and Subclinical Inflammation in Youth with Type 2 Diabetes

Abstract

Youth with type 2 diabetes (T2D-Y) have severe insulin resistance (IR) and increased risk for atherosclerotic cardiovascular disease (ASCVD). High levels of remnant triglyceride-rich lipoproteins (TRLp), the sum of small very low-density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) particles, may mediate this additional risk. Yet, the relationship of remnant TRLp with IR and inflammation in at-risk youth is unknown. We compared lipoprotein particles in 48 youth: 33 T2D-Y and 15 age/BMI matched peers without diabetes (age 15.5 ± 2.6 y, Tanner Stage IV-V, BMI 38.6 ± 7.4 kg/m2) and determined the relationship of remnant TRLp with IR and GlycA, a composite marker of inflammation. Fasting lipoprotein particle size and number, apolipoprotein B (apoB) and GlycA were derived from the NMR LipoProfile®. Insulin sensitivity was determined by the Matsuda index during a multi-sample 75g OGTT. T2D-Y had higher A1c (7.0 ± 1.2 vs. 5.6 ± 0.3%, P<0.01), lower Matsuda index (1.3 ± 1.0 vs. 2.5 ± 1.3, P<0.01) and higher GlycA (431 ± 73 vs. 390 ± 50 μmol/L, P=0.05). Triglyceride and low density (LDL) particles were higher in T2D-Y (ApoB: 74 ± 16 vs. 56 ± 12 mg/dL; total LDL particles: 1314 ± 298 vs. 983 ± 224 nmol/L; small LDL particles: 881 ± 348 vs. 492 ± 235 nmol/L; total TRLps: 111 ± 52 vs. 71 ± 30 nmol/L, and remnant TRLps: 97 ± 45 vs. 63 ± 29 nmol/L, all P<0.01). HDL particles were not different between groups. Matsuda index inversely correlated with GlycA (r=-0.4, P=0.01), total and remnant TRLps (both r=-0.5, P<0.01) and small LDL particles (r=-0.4, P=0.03), but not with total LDL or HDL particles. GlycA was associated with small LDLp (r=0.3, P=0.07 and remnant TRLp (all r=0.2, P=0.1) but this was not statistically significant. The high-risk profile marked by high remnant TRLps and small LDL particles in T2D-Y was associated with IR and an inflammatory marker, supporting the need for longitudinal studies to determine whether reducing TRLps and inflammation will reduce ASCVD risk. Disclosure A. Villalobos-perez: None. S. T. Chung: None. A. Zenno: None. C. K. Cravalho: None. S. Matta: None. A. B. Courville: None. L. Mabundo: None. V. R. Sharma: None. J. M. Dawson: None. M. W. Haymond: Advisory Panel; Self; Daiichi Sankyo, Zealand Pharma A/S, Other Relationship; Self; AstraZeneca, Stock/Shareholder; Self; Xeris Pharmaceuticals, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases