Greater Predicted Risk for Fatal/Non-fatal Cardiac Events in Youth-onset Type 2 Diabetes

Authors

• RW Robey
• CM Fitzsimmons
• WM Guiblet
• WJE Frye
• JM Gonz√°lez Dalmasy
• L Wang
• DA Russell
• AJ Perciaccante
• CC Lipsey
• AV Mitchell
• SS Maligireddy
• D Butcher
• EF Edmondson
• LM Jenkins
• AD Piscopio
• RA Totah
• SE Bates
• HE Arda
• MM Gottesman
• PJ Batista

Abstract

Youth-onset type 2 diabetes (YT2D) is characterized by severe insulin resistance, elevated triglyceride concentrations, and low HDL-cholesterol (-C). 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. We hypothesized that YT2D would have higher remnant TRLp, remnant-C, and greater subclinical inflammation and insulin resistance compared to healthy peers with obesity.

We measured fasting lipoprotein particle size and number, GlycA, and lipoprotein insulin resistance index (LPIR) 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).
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 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).

The proatherogenic profile in YT2D is characterized by higher small LDLp, remnant TRLp, and remnant-C and is related to insulin resistance and subclinical inflammation compared to healthy peers with obesity. Future research should determine whether reducing pro-atherogenic lipoproteins and inflammation will reduce ASCVD risk.

Scientific Focus Area: Clinical Research

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