Measurement of serum apolipoprotein levels in apolipoprotein-defined lipoprotein subclasses (ADLS) may have an important role in predicting vascular complications in type 1 diabetes (T1D), according to the results of a hypothesis-generating prospective study published in the Journal of Lipid Research.

Serum lipids and apolipoproteins concentrations are important biomarkers of cardiovascular disease, and serum apolipoprotein levels, as well as ADLS, may aid in predicting vascular complications in T1D. ADLS analysis defines particles according to their qualitative apolipoprotein complement and divides them into two families. The subclass names reflect the apolipoproteins present on the particle.

The goal of this study was to investigate the association of serum apolipoproteins and ADLS with cardiovascular events in patients with T1D.

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The study included 465 patients from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort and used fasting samples from years 4 to 6 of EDIC (1997-2000). Apolipoproteins were quantified by electro-immunoassays for APOA1, APOA2, APOB, APOC3, and APOE.

The main outcomes included any cardiovascular disease (myocardial infarction, stroke, confirmed angina, silent myocardial infarction, revascularization, congestive heart failure, or cardiovascular death) and major adverse cardiac events (MACE), which measured only fatal or nonfatal myocardial infarction or stroke.

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By the end of 2013, there were 50 cardiovascular events of any form over a follow-up of 5942 patient-years (8.4 events per 1000 individuals for 1 year) and 24 MACE events over a follow-up of 6180 patient-years (3.9 events per 1000 individuals for 1 year).

In adjusted analyses, APOC3 and its subfractions (heparin precipitate, heparin soluble) showed the most consistent and nominally significant association with risk for any cardiovascular event and MACE.

Among the other apolipoproteins measured, APOB showed a positive association with any cardiovascular events, but not with MACE. Among the ADLS biomarkers, only lipoprotein B demonstrated a positive association with any cardiovascular event. However, following adjustment for age, triglycerides, and glycated hemoglobin, no biomarkers were associated with MACE.

The researchers detailed several study limitations, including inclusion of only a subset of the EDIC cohort because of assay cost issues, possible limitations related to adjustment for confounders in the prospective analyses, and lack of adjustment for repeated testing.

“These associations provide information beyond that yielded by conventional lipid/lipoprotein measures, and may help to elucidate new biomarkers, pathogenic mechanisms and therapeutic targets for the prevention of cardiovascular events in type 1 diabetes,” concluded the researchers.

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Basu A, Bebu I, Jenkins AJ, et al. Serum apolipoproteins and apolipoprotein-defined lipoprotein subclasses: a hypothesis-generating prospective study of cardiovascular events in type 1 diabetes [published online June 15, 2019]. J Lipid Res. doi:10.1194/jlr.P090647