Atherogenic lipoproteins associate with loss of glycemic control in youth-onset type 2 diabetes: Results from the TODAY study

Authors: LEVITT KATZ, LORRAINE - Children'S Hospital - Philadelphia, Pennsylvania; GIDDING, SAMUEL - Geisinger Medical Center; OTVOS, JAMES - National Heart, Lung And Blood Institute(NHLBI, NIH); DREWS, KIMBERLY - George Washington University; BACHA, FIDA - Children'S Nutrition Research Center (CNRC); WILLI, STEVEN - Children'S Hospital - Philadelphia, Pennsylvania; MARCOVINA, SANTICA - University Of Washington; MCKAY, SIRIPOOM - Baylor College Of Medicine; WEINSTOCK, RUTH - Suny College

Submitted to: Journal of Clinical Lipidology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/31/2025
Publication Date: 2/6/2025
Citation: Levitt Katz, L.E., Gidding, S.S., Otvos, J.D., Drews, K.L., Bacha, F., Willi, S., Marcovina, S., Mckay, S., Weinstock, R.S. 2025. Atherogenic lipoproteins associate with loss of glycemic control in youth-onset type 2 diabetes: Results from the TODAY study. Journal of Clinical Lipidology. (2025)1-10. https://doi.org/10.1016/j.jacl.2025.01.005.
DOI: https://doi.org/10.1016/j.jacl.2025.01.005

Interpretive Summary: Adolescents with type 2 diabetes (T2D) often have unhealthy cholesterol levels, but detailed information on specific cholesterol particles called lipoproteins and certain amino acids is limited. The study aimed to track changes in cholesterol particles, insulin resistance index related to lipoproteins (LP-IR), and certain amino acids (BCAA) over time in adolescents with T2D, and see how these changes relate to sex, race/ethnicity, treatment, and worsening blood sugar control. The study followed 348 adolescents with T2D, analyzing their blood samples yearly for three years.At the start, participants were around 13.7 years old, mostly from minority groups, and had obesity. Certain cholesterol particle sizes and higher LP-IR scores were linked to worsening blood sugar control. Over three years, the number of cholesterol particles increased, and LP-IR and BCAA levels were higher in those with worsening blood sugar control. Females had larger HDL particles than males, and Non-Hispanic Blacks had different cholesterol particle sizes and lower LP-IR and BCAA levels compared to others. In summary, the investigators found that adolescents with T2D showed worsening cholesterol profiles over three years, which may contribute to early heart disease. Higher LP-IR and BCAA levels were associated with worsening blood sugar control. Implications: Understanding the differences in cholesterol particle sizes and insulin resistance in youth can help develop more targeted treatments and management strategies.

Technical Abstract: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce. To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D. Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments. At baseline, participants with were 13.7 years old with T2D, obesity, and from racial and ethnic minority groups (32.2% Non-Hispanic Black [NHB], 43.7% Hispanic). Smaller low-density lipoprotein (LDL) and larger very low-density lipoprotein (VLDL) sizes, higher high-density lipoprotein (HDL) particle number, and increased LP-IR score predicted worsening of glycemic control. LDL, HDL, and VLDL particle numbers increased over 3 years with weaker trends for decreasing LDL and HDL size. LP-IR and BCAA levels were higher longitudinally in those who lost glycemic control. Females had larger HDL size than males at baseline and throughout. NHBs had the largest LDL and HDL sizes, smaller VLDL size, and lower LP-IR and BCAA. These data in youth with T2D demonstrate a progressive atherogenic lipoprotein phenotype over 3 years. Increased LP-IR and BCAA are associated with worsening glycemic control and may be contributing to the premature development of atherosclerosis in youth with T2D.