Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease (CVD), largely by alterations in the blood lipids and the metabolism of circulating lipoproteins (LPs). We studied whether the presence of additional risk factors, such as hypertension, or CVD itself, is associated with further alterations in the LP profiles in individuals with T2DM. METHODS: We performed LP profiling using (1)H NMR spectroscopy and quantified 65 parameters in 393 healthy controls (HC) and in 390 T2DM patients with and without cardiovascular comorbidities. Univariate and multivariate analyses were used to assess alterations in LPs in diabetic patients. RESULTS: Triglycerides in all major LP classes, as well as particle numbers of very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL) were increased in T2DM compared to HC. In contrast, particle numbers of low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were reduced, suggesting slower lipolytic conversion of IDL to LDL and impaired clearance of triglyceride-enriched HDL. Univariate and multivariate analyses converged in identifying distinct LP profiles associated with T2DM, while differences between patients with and without hypertension or CVD were minor, indicating that T2DM is the primary factor driving LP dysregulation. T2DM, with or without cardiovascular comorbidities, also causes differential disruption of the correlation structure among LPs. CONCLUSIONS: T2DM is associated with major alterations in LP metabolism independent of hypertension or CVD. Thus, early lipid management in T2DM is important to mitigate CVD risk. Further research is needed to elucidate how T2DM progresses to CVD in relation to atherogenic LPs.