DOI: 10.1161/circ.148.suppl_1.13940 ISSN: 0009-7322

Abstract 13940: Remnant Lipoprotein Particles and Cholesterol Contribute to Proatherogenic Phenotype and Subclinical Inflammation in Youth-Onset Type 2 Diabetes

Aruba Chowdhury, Faith Davis, Andrea Krenek, Sydney Dixon, Lilian Mabundo, Stephanie T Chung
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Youth-onset type 2 diabetes (YT2D) is a rapidly progressive disease characterized by severe insulin resistance (IR), elevated triglyceride concentrations, and low HDL-cholesterol (-C). However, the contribution of triglyceride-rich remnant lipoproteins (TRLp) and remnant-C to overall atherogenic risk in YT2D is unknown, especially in the absence of clinically relevant elevations in LDL-C.

Hypothesis: We hypothesized that YT2D would have higher remnant TRLp, remnant-C, and greater subclinical inflammation and IR compared to healthy peers with obesity.

Methods: We measured fasting lipoprotein particle size and number, GlycA (a composite marker of inflammation), and lipoprotein IR index (LPIR) using NMR LipoProfile® in 61 YT2D (age 17.2 ±2.9 y, mean±SD, BMI 39.1 ±8.4 kg/m2) and 25 healthy peers (age 17.9 ± 5.1 y, BMI 35.8 ±5.7 kg/m2). Remnant Lp (small TRLp plus very small TRLp) and remnant-C (total-C minus HDL-C minus LDL-C) were calculated and the relationship with GlycA and LPIR determined by spearman correlations.

Results: YT2D had higher HemoglobinA1c (7.6 ± 2.0 vs 5.8 ± 0.8%), GlycA (427 [388, 474] vs 376 [332, 406] nmol/L, median[25th,75th]), LPIR (53.7 ± 23.6 vs 29.6 ± 16.5). YT2D had higher remnant TRLp and remnant-C (Figure 1) and a more proatherogenic lipid and lipoprotein profile: LDL-C: 89 ± 23 vs 74 ± 20 mg/dL; total LDLp: 1392 ±368 vs 1075 ±289 nmol/L; small LDLp: 890 ±450 vs 519 ±232 nmol/L, all P<0.01. LPIR was associated with remnant-C (r=0.6, P<0.001) but not with LDL-C (r=0.1, P=0.6). GlycA was associated with remnant-C, remnant TRLp, and small LDLp (all r≥0.3, P<0.01).

Conclusion: The proatherogenic profile in YT2D is characterized by higher small LDLp, remnant TRLp, and remnant-C and is related to IR and subclinical inflammation compared to healthy peers with obesity. Future research is needed to determine whether reducing all proatherogenic lipoproteins and inflammation will reduce ASCVD risk.

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