Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children.

BackgroundGlycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses.MethodsNuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (n = 75), post-treatment subacute (n = 36) and convalescent (n = 63) KD, as well as febrile controls (n = 48), and age-similar healthy controls (n = 48).ResultsGlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUC = 0.789-0.884), the combinations of GlycA and LDL-P (AUC = 0.909) or GlycA and the LDL-P/HDL-P ratio (AUC = 0.910) were best at discerning KD in patients 6-10 days after illness onset.ConclusionsHigh levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients

Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score:Associations with subclinical atherosclerosis and incident cardiovascular disease

BACKGROUND: The triglyceride/HDL cholesterol (TG/HDL-C) ratio and the Lipoprotein Insulin Resistance (LP-IR) score are lipid markers of insulin resistance. Their associations with carotid intima media thickness (cIMT; subclinical atherosclerosis) and incident cardiovascular disease (CVD) have not been thoroughly investigated.METHODS: In a cross-sectional cohort (89 subjects without type 2 diabetes (T2D) and 81 subjects with T2D we determined cIMT (ultrasound), homeostasis model assessment of insulin resistance (HOMA-IR) and the TG/HDL-C ratio. The LP-IR score, based on 6 lipoprotein characteristics determined by nuclear magnetic resonance spectroscopy, was measured in 123 participants. A prospective study was carried out among 6232 participants (Prevention of REnal and Vascular ENd-stage Disease study).RESULTS: Cross-sectionally, the adjusted associations of HOMA-IR, the TG/HDL-C ratio and the LP-IR score with cIMT were approximately similar (standardized β = 0.34 (95 % CI 0.19-0.48), 0.24 (95 % CI 0.09-039) and 0.41 (95 % CI 0.23--0.59), respectively). Prospectively, 507 new cases of CVD were observed after a median follow-up of 8.2 (interquartile range 7.5-8.8) years. HOMA-IR, the TG/HDL-C ratio and LP-IR were each associated with incident CVD independent of potential confounders (HR 1.12, 95 % CI 1.02-1.24;1.22, 95 % CI 1.11-1.35 and 1.15. 95 % CI 1.01-1.31, respectively). The association of the TG/HDL-C ratio with incident CVD was somewhat stronger than that of HOMA-IR.CONCLUSION: Lipoprotein-based markers of insulin resistance are at least as strongly associated with subclinical atherosclerosis and clinical atherosclerosis development as HOMA-IR, obviating the need to measure insulin to determine the impact of insulin resistance. For practical purposes, the easily obtainable TG/HDL-C ratio may suffice.</p

A metabolomic index based on lipoprotein subfractions and branched chain amino acids is associated with incident hypertension

OBJECTIVE: The present study aims to evaluate the performance of the Diabetes Risk Index (DRI), a metabolomic index based on lipoprotein particles and branched chain amino acids, on the incidence of newly developed hypertension in a large community dwelling cohort. METHODS: The DRI was calculated by combining 6 lipoprotein parameters [sizes of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), concentrations of large VLDL, small LDL, and large HDL particles], and the concentrations of valine and leucine. DRI scores were estimated in 4169 participants from the PREVEND prospective cohort. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident hypertension. RESULTS: During a median follow-up of 8.6 years, 924 new hypertension cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI and incident hypertension with a hazard ratio (HR) per 1 SD increase of 1.45 (95% CI 1.36,1.54; p < 0.001). After additional adjustment for traditional risk factors, the HR remained significant (HRadj 1.21, 95% CI 1.10, 1.33, p <0.001). Likewise, subjects in the top quartile of DRI presented with a higher risk of hypertension (HRadj 1.64, 95% CI 1.28, 2.10, p <0.001). Furthermore, the net reclassification improvement assessment improved after the addition of DRI to a traditional risk model (p <0.001), allowing proper reclassification of 34% of the participants. CONCLUSION: Higher DRI scores were associated with an increased risk of incident hypertension. Such association was independent of traditional clinical risk factors for hypertension

Nuclear Magnetic Resonance-Measured Ionized Magnesium Is Inversely Associated with Type 2 Diabetes in the Insulin Resistance Atherosclerosis Study

The aims were to optimize a nuclear magnetic resonance (NMR)-based assay for quantifying ionized or free magnesium and investigate its association with type 2 diabetes (T2D). A high-throughput, ionized magnesium assay was optimized and evaluated. Plasma magnesium was quantified, and associations with T2D were ascertained in Insulin Resistance Atherosclerosis Study (IRAS) participants. Coefficients of variation for the ionized magnesium assay ranged from 0.7–1.5% for intra-assay and 4.2–4.7% for inter-assay precision. In IRAS (n = 1342), ionized magnesium was significantly lower in subjects with prediabetes and T2D than in normoglycemic subjects, and lower in participants with T2D than those with prediabetes (p < 0.0001). Cross-sectional regression analyses revealed that magnesium was associated with T2D at baseline in models adjusted for multiple clinical risk factors (p = 0.032). This association appeared to be modified by sex, in such a way that the associations were present in women (OR = 0.54 (95% CI 0.37–0.79), p = 0.0015) and not in men (OR = 0.98 (95% CI 0.71–1.35), p = 0.90). Longitudinal regression analyses revealed an inverse association between magnesium and future T2D in the total population (p = 0.035) that was attenuated by LP-IR (p = 0.22). No interactions were detected between magnesium and age, race, BMI, glucose, insulin, triglycerides, or LPIR for the prospective association with future T2D. However, a significant interaction between magnesium and sex was present, now with a trend for an association in men (OR = 0.75 (95% CI 0.55–1.02), p = 0.065 and absence of an association in women (OR = 1.01 (0.76–1.33), p = 0.97). Conclusions: lower ionized magnesium, as measured by an NMR-based assay optimized for accuracy and precision, was associated cross-sectionally with T2D at baseline and longitudinally with incident T2D in IRAS

Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score:Associations with subclinical atherosclerosis and incident cardiovascular disease

BACKGROUND: The triglyceride/HDL cholesterol (TG/HDL-C) ratio and the Lipoprotein Insulin Resistance (LP-IR) score are lipid markers of insulin resistance. Their associations with carotid intima media thickness (cIMT; subclinical atherosclerosis) and incident cardiovascular disease (CVD) have not been thoroughly investigated.METHODS: In a cross-sectional cohort (89 subjects without type 2 diabetes (T2D) and 81 subjects with T2D we determined cIMT (ultrasound), homeostasis model assessment of insulin resistance (HOMA-IR) and the TG/HDL-C ratio. The LP-IR score, based on 6 lipoprotein characteristics determined by nuclear magnetic resonance spectroscopy, was measured in 123 participants. A prospective study was carried out among 6232 participants (Prevention of REnal and Vascular ENd-stage Disease study).RESULTS: Cross-sectionally, the adjusted associations of HOMA-IR, the TG/HDL-C ratio and the LP-IR score with cIMT were approximately similar (standardized β = 0.34 (95 % CI 0.19-0.48), 0.24 (95 % CI 0.09-039) and 0.41 (95 % CI 0.23--0.59), respectively). Prospectively, 507 new cases of CVD were observed after a median follow-up of 8.2 (interquartile range 7.5-8.8) years. HOMA-IR, the TG/HDL-C ratio and LP-IR were each associated with incident CVD independent of potential confounders (HR 1.12, 95 % CI 1.02-1.24;1.22, 95 % CI 1.11-1.35 and 1.15. 95 % CI 1.01-1.31, respectively). The association of the TG/HDL-C ratio with incident CVD was somewhat stronger than that of HOMA-IR.CONCLUSION: Lipoprotein-based markers of insulin resistance are at least as strongly associated with subclinical atherosclerosis and clinical atherosclerosis development as HOMA-IR, obviating the need to measure insulin to determine the impact of insulin resistance. For practical purposes, the easily obtainable TG/HDL-C ratio may suffice.</p

Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score:Associations with subclinical atherosclerosis and incident cardiovascular disease

BACKGROUND: The triglyceride/HDL cholesterol (TG/HDL-C) ratio and the Lipoprotein Insulin Resistance (LP-IR) score are lipid markers of insulin resistance. Their associations with carotid intima media thickness (cIMT; subclinical atherosclerosis) and incident cardiovascular disease (CVD) have not been thoroughly investigated.METHODS: In a cross-sectional cohort (89 subjects without type 2 diabetes (T2D) and 81 subjects with T2D we determined cIMT (ultrasound), homeostasis model assessment of insulin resistance (HOMA-IR) and the TG/HDL-C ratio. The LP-IR score, based on 6 lipoprotein characteristics determined by nuclear magnetic resonance spectroscopy, was measured in 123 participants. A prospective study was carried out among 6232 participants (Prevention of REnal and Vascular ENd-stage Disease study).RESULTS: Cross-sectionally, the adjusted associations of HOMA-IR, the TG/HDL-C ratio and the LP-IR score with cIMT were approximately similar (standardized β = 0.34 (95 % CI 0.19-0.48), 0.24 (95 % CI 0.09-039) and 0.41 (95 % CI 0.23--0.59), respectively). Prospectively, 507 new cases of CVD were observed after a median follow-up of 8.2 (interquartile range 7.5-8.8) years. HOMA-IR, the TG/HDL-C ratio and LP-IR were each associated with incident CVD independent of potential confounders (HR 1.12, 95 % CI 1.02-1.24;1.22, 95 % CI 1.11-1.35 and 1.15. 95 % CI 1.01-1.31, respectively). The association of the TG/HDL-C ratio with incident CVD was somewhat stronger than that of HOMA-IR.CONCLUSION: Lipoprotein-based markers of insulin resistance are at least as strongly associated with subclinical atherosclerosis and clinical atherosclerosis development as HOMA-IR, obviating the need to measure insulin to determine the impact of insulin resistance. For practical purposes, the easily obtainable TG/HDL-C ratio may suffice.</p

Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score:Associations with subclinical atherosclerosis and incident cardiovascular disease

BACKGROUND: The triglyceride/HDL cholesterol (TG/HDL-C) ratio and the Lipoprotein Insulin Resistance (LP-IR) score are lipid markers of insulin resistance. Their associations with carotid intima media thickness (cIMT; subclinical atherosclerosis) and incident cardiovascular disease (CVD) have not been thoroughly investigated.METHODS: In a cross-sectional cohort (89 subjects without type 2 diabetes (T2D) and 81 subjects with T2D we determined cIMT (ultrasound), homeostasis model assessment of insulin resistance (HOMA-IR) and the TG/HDL-C ratio. The LP-IR score, based on 6 lipoprotein characteristics determined by nuclear magnetic resonance spectroscopy, was measured in 123 participants. A prospective study was carried out among 6232 participants (Prevention of REnal and Vascular ENd-stage Disease study).RESULTS: Cross-sectionally, the adjusted associations of HOMA-IR, the TG/HDL-C ratio and the LP-IR score with cIMT were approximately similar (standardized β = 0.34 (95 % CI 0.19-0.48), 0.24 (95 % CI 0.09-039) and 0.41 (95 % CI 0.23--0.59), respectively). Prospectively, 507 new cases of CVD were observed after a median follow-up of 8.2 (interquartile range 7.5-8.8) years. HOMA-IR, the TG/HDL-C ratio and LP-IR were each associated with incident CVD independent of potential confounders (HR 1.12, 95 % CI 1.02-1.24;1.22, 95 % CI 1.11-1.35 and 1.15. 95 % CI 1.01-1.31, respectively). The association of the TG/HDL-C ratio with incident CVD was somewhat stronger than that of HOMA-IR.CONCLUSION: Lipoprotein-based markers of insulin resistance are at least as strongly associated with subclinical atherosclerosis and clinical atherosclerosis development as HOMA-IR, obviating the need to measure insulin to determine the impact of insulin resistance. For practical purposes, the easily obtainable TG/HDL-C ratio may suffice.</p

Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index

Background: Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of beta-hydroxybutyrate (beta-HB), acetoacetate (AcAc) and acetone. Methods: The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). Results: beta-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R-2 = 0.996, 0.994, and 0.994 for beta-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for beta-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 t

Triglyceride/HDL cholesterol ratio and lipoprotein insulin resistance Score:Associations with subclinical atherosclerosis and incident cardiovascular disease

BACKGROUND: The triglyceride/HDL cholesterol (TG/HDL-C) ratio and the Lipoprotein Insulin Resistance (LP-IR) score are lipid markers of insulin resistance. Their associations with carotid intima media thickness (cIMT; subclinical atherosclerosis) and incident cardiovascular disease (CVD) have not been thoroughly investigated.METHODS: In a cross-sectional cohort (89 subjects without type 2 diabetes (T2D) and 81 subjects with T2D we determined cIMT (ultrasound), homeostasis model assessment of insulin resistance (HOMA-IR) and the TG/HDL-C ratio. The LP-IR score, based on 6 lipoprotein characteristics determined by nuclear magnetic resonance spectroscopy, was measured in 123 participants. A prospective study was carried out among 6232 participants (Prevention of REnal and Vascular ENd-stage Disease study).RESULTS: Cross-sectionally, the adjusted associations of HOMA-IR, the TG/HDL-C ratio and the LP-IR score with cIMT were approximately similar (standardized β = 0.34 (95 % CI 0.19-0.48), 0.24 (95 % CI 0.09-039) and 0.41 (95 % CI 0.23--0.59), respectively). Prospectively, 507 new cases of CVD were observed after a median follow-up of 8.2 (interquartile range 7.5-8.8) years. HOMA-IR, the TG/HDL-C ratio and LP-IR were each associated with incident CVD independent of potential confounders (HR 1.12, 95 % CI 1.02-1.24;1.22, 95 % CI 1.11-1.35 and 1.15. 95 % CI 1.01-1.31, respectively). The association of the TG/HDL-C ratio with incident CVD was somewhat stronger than that of HOMA-IR.CONCLUSION: Lipoprotein-based markers of insulin resistance are at least as strongly associated with subclinical atherosclerosis and clinical atherosclerosis development as HOMA-IR, obviating the need to measure insulin to determine the impact of insulin resistance. For practical purposes, the easily obtainable TG/HDL-C ratio may suffice.</p

A Newly Developed Diabetes Risk Index, Based on Lipoprotein Subfractions and Branched Chain Amino Acids, is Associated with Incident Type 2 Diabetes Mellitus in the PREVEND Cohort

Objective: Evaluate the ability of a newly developed diabetes risk score, the Diabetes Risk Index (DRI), to predict incident type 2 diabetes mellitus (T2D) in a large adult population. Methods: The DRI was developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from 6 lipoprotein subspecies and size parameters, and the branched chain amino acids, valine and leucine, all of which have been shown previously to be associated with future T2D. DRI scores were calculated in a total of 6134 nondiabetic men and women in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident T2D. Results: During a median follow-up of 8.5 years, 306 new T2D cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI scores and incident T2D with the hazard ratio (HR) for the highest versus lowest quartile being 12.07 (95% confidence interval: 6.97-20.89, p <0.001). After additional adjustment for body mass index (BMI), family history of T2D, alcohol consumption, diastolic blood pressure, total cholesterol, triglycerides, HDL cholesterol and HOMA-IR, the HR was attenuated but remained significant (HR 3.20 (1.73-5.95), p = 0.001). Similar results were obtained when DRI was analyzed as HR per 1 SD increase (HR 1.37 (1.14-1.65), p <0.001). The Kaplan-Meier plot demonstrated that patients in the highest quartile of DRI scores presented at higher risk (p-value for log-rank tes