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

ABSTRACT: 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.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.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.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.

SUBMITTER: Mora S

PROVIDER: S-EPMC2857895 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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

Mora Samia S Otvos James D JD Rosenson Robert S RS Pradhan Aruna A Buring Julie E JE Ridker Paul M PM

Diabetes 20100225 5

<h4>Objective</h4>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.<h4>Research design and methods</h4>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 ...[more]

PMID: 20185808

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Project description:BackgroundNuclear magnetic resonance (NMR) spectroscopy measures the number and size of lipoprotein particles instead of their cholesterol or triglyceride content, but its clinical utility is uncertain.Methods and resultsBaseline lipoproteins were measured by NMR in 27 673 initially healthy women followed up for incident cardiovascular disease (n=1015) over an 11-year period. After adjustment for nonlipid risk factors, hazard ratios and 95% confidence intervals for the top versus the bottom quintile of NMR-measured lipoprotein particle concentration (measured in particles per liter) were 2.51 (1.91 to 3.30) for low-density lipoprotein (LDL(NMR)), 0.91 (0.75 to 1.12) for high-density lipoprotein (HDL(NMR)), 1.71 (1.38 to 2.12) for very low-density lipoprotein (VLDL(NMR)), and 2.25 (1.80 to 2.81) for the LDL(NMR)/HDL(NMR) ratio. Similarly adjusted results for NMR-measured lipoprotein particle size (measured in nanometers) were 0.64 (0.52 to 0.79) for LDL(NMR) size, 0.65 (0.51 to 0.81) for HDL(NMR) size, and 1.37 (1.10 to 1.70) for VLDL(NMR) size. Hazard ratios for NMR measures were comparable but not superior to standard lipids (total cholesterol 2.08 [1.63 to 2.67], LDL cholesterol 1.74 [1.40 to 2.16], HDL cholesterol 0.52 [0.42 to 0.64], triglycerides 2.58 [1.95 to 3.41], non-HDL cholesterol 2.52 [1.95 to 3.25], total/HDL cholesterol ratio 2.82 [2.23 to 3.58]) and apolipoproteins (B(100) 2.57 [1.98 to 3.33], A-1 0.63 [0.52 to 0.77], and B(100)/A-1 ratio 2.79 [2.21 to 3.54]). Essentially no reclassification improvement was found with the addition of the LDL(NMR) particle concentration or apolipoprotein B(100) to a model that already included the total/HDL cholesterol ratio and nonlipid risk factors (net reclassification index 0% and 1.9%, respectively), nor did the addition of either variable result in a statistically significant improvement in the c-index.ConclusionsIn this prospective study of healthy women, cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of standard lipids or apolipoproteins.

Project description:BackgroundThe cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for cholesterol efflux capacity, perhaps mediated through efflux of cholesterol and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People with type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL-cholesterol concentrations. We therefore tested the hypothesis that small HDL particles (HDL-P)-rather than HDL-cholesterol-predict incident CAD in type 1 diabetes.Methods and resultsIncident CAD (CAD death, myocardial infarction, or coronary revascularization) was determined in 550 individuals with childhood-onset type 1 diabetes. HDL-P was quantified by calibrated ion mobility analysis and cholesterol efflux capacity was quantified with validated assays. During a median follow-up of 26 years, 36.5% of the participants developed incident CAD, for an incidence density of 181.3 per 10 000 person-years. In multivariable Cox models, neither HDL-cholesterol nor apolipoprotein A1 concentration was significantly associated with CAD risk. In contrast, higher extra-small HDL-P concentrations were significantly associated with decreased CAD risk (hazard ratio [HR], 0.26 [95% CI, 0.14-0.50]). Weaker associations were observed for total HDL-P (HR, 0.88 [95% CI, 0.83-0.93]), small HDL (HR, 0.83 [95% CI, 0.68-1.02]), medium HDL (HR, 0.79 [95% CI, 0.71-0.89]), and large HDL (HR, 0.72 [95% CI, 0.59-0.89]). Although cholesterol efflux capacity was negatively associated with incident CAD, this association was no longer significant after adjustment for total HDL-P.ConclusionsLower concentrations of total HDL-P and HDL subpopulations were positively associated with incident CAD independently of HDL-cholesterol, apolipoprotein A1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that extra-small HDL plays a critical role in cardioprotection in type 1 diabetes, mediated by macrophage cholesterol efflux by the ABCA1 pathway.

Project description:ObjectiveTo estimate the association between lipoprotein particle concentrations in pregnancy and gestational age at delivery.DesignProspective cohort study.SettingThe study was conducted in the USA at the University of North Carolina.PopulationWe assessed 715 women enrolled in the Pregnancy, Infection, and Nutrition study from 2001 to 2005.MethodsFasting blood was collected at two time points (<20 and 24-29 weeks of gestation). Nuclear magnetic resonance (NMR) quantified lipoprotein particle concentrations [low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low density lipoprotein (VLDL)] and 10 subclasses of lipoproteins. Concentrations were assessed as continuous measures, with the exception of medium HDL which was classified as any or no detectable level, given its distribution. Cox proportional hazards models estimated hazard ratios (HR) for gestational age at delivery adjusting for covariates.Main outcome measuresGestational age at delivery, preterm birth (<37 weeks of gestation), and spontaneous preterm birth.ResultsAt <20 weeks of gestation, three lipoproteins were associated with later gestational ages at delivery [large LDLNMR (HR 0.78, 95% CI 0.64-0.96), total VLDLNMR (HR 0.77, 95% CI 0.61-0.98), and small VLDLNMR (HR 0.78, 95% CI 0.62-0.98], whereas large VLDLNMR (HR 1.19, 95% CI 1.01-1.41) was associated with a greater hazard of earlier delivery. At 24-28 weeks of gestation, average VLDLNMR (HR 1.25, 95% CI 1.03-1.51) and a detectable level of medium HDLNMR (HR 1.90, 95% CI 1.19-3.02) were associated with earlier gestational ages at delivery.ConclusionIn this sample of pregnant women, particle concentrations of VLDLNMR , LDLNMR , IDLNMR , and HDLNMR were each independently associated with gestational age at delivery for all deliveries or spontaneous deliveries <37 weeks of gestation. These findings may help formulate hypotheses for future studies of the complex relationship between maternal lipoproteins and preterm birth.Tweetable abstractNuclear magnetic resonance spectroscopy may identify lipoprotein particles associated with preterm delivery.

Project description:BackgroundCholesterol efflux capacity (CEC) negatively correlates with cardiovascular disease risk. Small HDL particles account almost quantitively for CEC, perhaps mediated through efflux of outer leaflet plasma membrane phospholipids by ABCA1. People with type 1 diabetes (T1D) are at increased risk of coronary artery disease (CAD) despite normal levels of HDL-cholesterol (HDL-C). We therefore tested the hypotheses that small HDL particles (HDL-P)-rather than HDL-C levels-predict incident CAD in T1D.MethodsIncident CAD (CAD death, myocardial infarction, and/or coronary revascularization) was determined in a cohort of 550 participants with childhood-onset T1D. HDL-P was quantified by calibrated ion mobility analysis. CEC and phospholipid efflux were quantified with validated assays.ResultsDuring a median follow-up of 26 years, 36.5% of the participants developed incident CAD. In multivariable Cox models, levels of HDL-C and apolipoprotein A-I (APOA1) did not predict CAD risk. In contrast, extra-small HDL particle levels strongly and negatively predicted risk (hazard ratio [HR]=0.25, 95% confidence interval [CI]=0.13-0.49). An increased concentration of total HDL particles (T-HDL-P) (HR=0.87, CI=0.82-0.92) and three other HDL sizes were weaker predictors of risk: small HDL (HR=0.80, 0.65-0.98), medium HDL (HR=0.78, CI=0.70-0.87) and large HDL (HR=0.72, CI=0.59-0.89). Although CEC negatively associated with incident CAD, that association disappeared after the model was adjusted for T-HDL-P. Isolated small HDLs strongly promoted ABCA1-dependent efflux of membrane outer leaflet phospholipids.ConclusionsLow concentrations of T-HDL-P and all four sizes of HDL subpopulations predicted incident CAD independently of HDL-C, APOA1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that small HDLs play a critical role in cardioprotection in T1D, which might be mediated by macrophage plasma membrane outer leaflet phospholipid export and cholesterol efflux by the ABCA1 pathway.

Project description:Background Supplementation with omega-3 (n-3) fatty acid or dietary fish may protect against atherosclerosis, but the potential mechanisms are unclear. Prior studies found modest triglyceride-lowering effects and slight increases in LDL (low-density lipoprotein) cholesterol. Limited evidence has examined n-3 effects on more detailed lipoprotein biomarkers. Methods and Results We conducted a study of 26 034 healthy women who reported information on fish and n-3 intake from a 131-item food-frequency questionnaire. We measured plasma lipids, apolipoproteins, and nuclear magnetic resonance spectroscopy lipoproteins and examined their associations with dietary intake of fish, total n-3, and the n-3 subtypes (eicosapentaenoic, docosahexaenoic, and α-linolenic acids). Top- versus bottom-quintile intake of fish and n-3 were significantly associated with lower triglyceride and large VLDL (very-low-density lipoprotein) particles. Fish intake, but not total n-3, was positively associated with total cholesterol, LDL cholesterol, apolipoprotein B, and larger LDL size, but only α-linolenic acid was associated with lower LDL cholesterol. Total n-3, docosahexaenoic acid, and α-linolenic acid intake were also positively associated with larger HDL (high-density lipoprotein) size and large HDL particles. High eicosapentaenoic acid intake was significantly associated with only a decreased level of VLDL particle concentration and VLDL triglyceride content. The n-3 fatty acids had some similarities but also differed in their associations with prospective cardiovascular disease risk patterns. Conclusions Higher consumption of fish and n-3 fatty acids were associated with multiple measures of lipoproteins that were mostly consistent with cardiovascular prevention, with differences noted for high intake of eicosapentaenoic acid versus docosahexaenoic acid and α-linolenic acid that were apparent with more detailed lipoprotein phenotyping. These hypothesis-generating findings warrant further study in clinical trials. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.

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

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

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