Lipoprotein particle size and concentration by nuclear magnetic resonance and incident type 2 diabetes in women

Abstract

Objective: Diabetic dyslipoproteinemia is characterized by low HDL cholesterol and high triglycerides. We examined the association of lipoprotein particle size and concentration measured by nuclear magnetic resonance (NMR) spectroscopy with clinical type 2 diabetes.

Research design and methods: This was a prospective study of 26,836 initially healthy women followed for 13 years for incident type 2 diabetes (n = 1,687). Baseline lipids were measured directly and lipoprotein size and concentration by NMR. Cox regression models included nonlipid risk factors (age, race, smoking, exercise, education, menopause, blood pressure, BMI, family history, A1C, and C-reactive protein). NMR lipoproteins were also examined after further adjusting for standard lipids.

Results: Incident diabetes was significantly associated with baseline HDL cholesterol, triglycerides, and NMR-measured size and concentration of LDL, IDL, HDL, and VLDL particles. The associations of these particles differed substantially by size. Small LDL(NMR) and small HDL(NMR) were positively associated with diabetes (quintile 5 vs. 1 [adjusted hazard ratios and 95% CIs], 4.04 [3.21-5.09] and 1.84 [1.54-2.19], respectively). By contrast, large LDL(NMR) and large HDL(NMR) were inversely associated (quintile 1 vs. 5, 2.50 [2.12-2.95] and 4.51 [3.68-5.52], respectively). For VLDL(NMR), large particles imparted higher risk than small particles (quintile 5 vs. 1, 3.11 [2.35-4.11] and 1.31 [1.10-1.55], respectively). Lipoprotein particle size remained significant after adjusting for standard lipids and nonlipid factors.

Conclusions: In this prospective study of women, NMR lipoprotein size and concentrations were associated with incident type 2 diabetes and remained significant after adjustment for established risk factors, including HDL cholesterol and triglycerides.

FIG. 1.

Adjusted HRs and 95% CIs for quintile 5 vs. 1, unless otherwise noted, adjusted for nonlipid risk factors (age, race, randomized treatment assignment, smoking, exercise, education, menopausal status, hormone use, blood pressure, BMI, family history of diabetes, A1C, and hsCRP). A1C results were adjusted for age, race, randomized treatment assignment, smoking, exercise, education, menopausal status, hormone use, blood pressure, BMI, family history of diabetes, hsCRP, and standard lipids.

FIG. 2.

HRs and 95% CIs were adjusted similar to Fig. 1 and stratified according to fasting (black circles) or nonfasting (gray diamonds) status.