Background: Apolipoproteins Apo-B, Apo-C-III, and Apo-E are atherogenic and are associated with diabetic dyslipidemia and cardiovascular disease (CVD). Apolipoprotein-defined lipoprotein subclasses (ADLS) also show associations with CVD, but prospective associations of these detailed metrics with CVD in people with type 1 diabetes (T1DM) have not been explored.

Objective: Prospective associations of serum apolipoproteins and ADLS with CVD and major atherosclerotic cardiovascular events (MACE: composite of CVD death, nonfatal myocardial infraction or nonfatal stroke) in T1DM.

Methods: Serum apolipoproteins and ADLS (14 biomarkers in total) measured in sera (1997-2000) in a subset (n=465) of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of CVD and MACE over 5942 and 6180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models unadjusted and adjusted for risk factors.

Results: During 15 years follow-up, 50 CVD and 24 MACE events occurred. Significant positive univariate associations for CVD were: Lp-B, Apo-B, Apo-C-III (total, heparin precipitate (HP), i.e., Apo-C-III in VLDL, and heparin soluble (HS), i.e., Apo-C-III in HDL) and Lp-B:C; for MACE: Apo-C-III sub fractions (total, Apo-C-III-HP, and Apo-C-III-HS). Adjusting for sex, age, HbA1c, systolic blood pressure, pulse rate, LDL-cholesterol, and triglycerides: for CVD, Apo-C-III-HS remained significant (HR (95% CI): 1.18 (1.03, 1.35); P=0.01). For MACE, total Apo-C-III and Apo-C-III-HS persisted when adjusted for age, HbA1c and LDL [1.11 (1.01, 1.22); P=0.02, and 1.22 (1.02, 1.45); P=0.02, respectively], but not for age, HbA1c and (log) triglycerides. No significant associations of other ADLS, Apo-A-I, A-II and Apo-E with CVD/MACE were observed.

Conclusions: Total serum Apo-C-III and Apo-C-III in HDL and Apo-B-containing lipoproteins may serve as predictive biomarkers for CVD events in T1DM adults.


A. Basu: None. I. Bebu: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. J. Stoner: None. Y. Zhang: None. R.L. Klein: None. M.F. Lopes-Virella: None. W. Garvey: Advisory Panel; Self; Novo Nordisk Inc., Merck & Co., Inc.. Research Support; Self; Sanofi, Pfizer Inc., Novo Nordisk Inc., AstraZeneca, Merck & Co., Inc., Elcelyx Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Eisai Inc. M. Budoff: Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Amarin Corporation. T. Lyons: None.

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