Dyslipidemia of Insulin Resistance Is Associated with Subclinical Inflammation in Youth with Type 2 Diabetes

The dyslipidemia of insulin resistance (IR), characterized by high triglyceride-rich lipoproteins (TRLP) and low high-density lipoproteins (HDL), is associated with systemic inflammation, small low-density lipoproteins (LDL) and are important risk factors for atherosclerotic disease (ASCVD) in adults. Yet, in youth with type 2 diabetes (T2D) the natural history of ASCVD and the role of low-grade inflammation is still emerging. We compared lipoprotein profiles and inflammatory markers in 21 youth with T2D, within 5 years of diagnosis, to 10 age/BMI matched control youth with normal glucose tolerance (age: 15.8±2.5 (10-23 y) mean±SD (range), Tanner Stage IV-V, BMI: 38.9±6.9 (27.1-57.8 kg/m2). Fasting lipoprotein particle size and number, apolipoprotein B (apoB), and GlycA, a composite marker of inflammation, were derived from the NMR LipoProfile®. Pro-inflammatory markers were measured with multi-plex ELISA assays (C-Reactive Protein (hsCRP), IL-6, IL-8, IL-1β, TNF-alpha). IR was calculated by the Matsuda index during a multi-sample 75g OGTT. Youth with T2D, had higher A1c (7.2±1.3 vs. 5.4±0.3%, P<0.01), lower Matsuda index (1.3±1.2 vs. 2.8±1.4, P<0.01), higher ApoB (75.8±17.5 vs. 50.8±9.2 mg/dL, P<0.01), more small LDL (903.4±413.3 vs. 575.8±146.4 nmol/L, P=0.02) and higher TRLPs particle concentrations (121.3±45 vs. 70.4±30.9 nmol/L, P<0.01). HDL particles were not different between groups. GlycA (439.7±77.8 vs. 363.6±46.7 μmol/L, P=0.01) and hsCRP (0.8±0.9 vs. 0.2±0.2 μmol/L, P=0.01) were higher in T2D, but there were no differences in other inflammatory markers. Both GlycA and hsCRP correlated with small LDL and TRLP (GlycA: both r=0.4, P<0.05); hsCRP: both r=0.5, P<0.01), but not with HDL. The dyslipidemic profile of IR in youth with T2D was associated with subclinical inflammation, supporting the need for longitudinal studies to determine whether reducing inflammation in these youth will be effective as an ASCVD risk reduction strategy. Disclosure A. Villalobos-Perez: None. C.K. Cravalho: None. S. Matta: None. A. Meyers: None. L. Mabundo: None. M.L. Sampson: None. M. Walter: None. A.B. Courville: None. S.T. Chung: None. Funding National Institutes of Health (to S.T.C., L.M., A.B.C.)